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TABLE OF CONTENTS

Introduction . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . 1

Chapter 1          Advances in Treatment . . . . . . . . . . . . . . . . . . 3

Chapter 2          Research and Development . . . . . . . . . . . . . 13

Chapter 3          Spending and Costs. . . . . . . . . . . . . . . . . . . . 32

Chapter 4          Outcomes and Savings . . . . . . . . . . . . . . . . . .47

Chapter 5          Marketing and Promotion. . . . . . . . . . . . . . . 62

Chapter 6          Economic Impact . . . . . . . . . . . . . . . . . . . . . . 73
INTRODUCTION

This chart pack provides facts and figures about prescription
medicines and their role in the health care system. Topics
include medicines’ impact on health and quality of life, the
drug discovery and development process, biopharmaceutical
spending and costs, the challenge of treatment gaps and
improving use of prescribed therapies, the marketing and
promotion of medicines, and the role of the biopharmaceutical
sector in the U.S. economy.

Data and information found in this publication were drawn
from a wide range of sources, including government agency
reports, peer-reviewed journals, and the Pharmaceutical
Research and Manufacturers of America’s (PhRMA’s) own
research and analysis. PhRMA hopes this publication provides
useful context for discussions about the role of medicines in
the U.S. health care system.




                                                                1
DR TORSTEN WITTMANN/SCIENCE PHOTO LIBRARY
1   ADVANCES IN
                                TREATMENT
                                Medicines’ Impact on Health and Quality of Life

                                Prescription medicines play a large role in saving and
                                improving lives. Over the last 25 years, prescription
                                medicines have significantly reduced deaths from major
                                diseases such as heart disease, several cancers, and
                                HIV/AIDS. They have also improved the quality of life for
                                people suffering from conditions such as arthritis and
                                Alzheimer’s disease. Recent advances have included, for
                                example, entirely new classes of treatments for diabetes,
                                hypertension, and HIV/AIDS; a new generation of
                                personalized medicines; and the very first treatments
                                for a number of rare diseases, such as Pompe disease
                                and Hunter syndrome. As our population ages and faces
                                increased rates of disease, medical advances will be key
                                to alleviating suffering.




1 • Advances in Treatment                                                                   3
U.S. Life Expectancy 1950–2011*
“While nutrition, sanitation, other public health measures, and expanded access to care have been major sources
of increasing human health, innovative medicines have also played a profound role in this progress.”
                                                                     — The President’s Committee of Advisors on Science and Technology1



                                85

                                                                                                                                         81.1
                                                                                                  78.8              79.3
                                80
                                                                                           77.4
                                                                                                                                         76.3
          At Birth (in Years)




                                                                     74.7                                           74.1
                                75              73.1
                                                                                                  71.8
                                     71.1
                                                                                           70
                                70
                                                66.6                 67.1
                                     65.6
                                65
                                                                                                                               Women
                                                                                                                               Men


                                60
                                     1950       1960                 1970                  1980   1990              2000                 2011

 *Life expectancies prior to 1997 were calculated using a slightly different methodology
 than for those post-1997.                                                                          Source: U.S. Centers for Disease Control and Prevention (CDC)2


1 • Advances in Treatment                                                                                                                                       4
Cardiovascular Disease:
Declining Rates of Death and Heart Failure
“Factors contributing to the decline in heart disease and stroke mortality include better control of risk factors,
improved access to early detection, and better treatment and care, including new drugs and expanded uses for
existing drugs.”
                                                               — U.S. Centers for Disease Control and Prevention3

                                                                        U.S. Death Rates Due to Diseases of the Heart*
                                         450
                                               401.6 397.0
                                                           388.9
                                                                    375.0
  Age-adjusted Death Rates per 100,000




                                         400
                                                                            355.9
                                                                                    332.0
                                         350                                                313.8 309.9
                                                                                                          296.3
                                         300                                                                      280.4
                                                                                                                          266.5
                                                                                                                                  247.8
                                                                                                                                          232.3
                                         250                                                                                                      211.1
                                                                                                                                                          190.9 180.1
                                         200                                                                                                                          173.7

                                         150

                                         100

                                         50

                                          0
                                               1979   1981   1983   1985    1987    1989    1991   1993   1995    1997    1999    2001    2003    2005    2007   2009    2011

 *Age-adjusted death rates based on Year 2000 U.S. Standard Population. 1980–1998 causes of death are classified by
 the Ninth Revision International Classification of Diseases (ICD-9). Beginning in 1999, causes of death are classified by
 the Tenth Revision International Classification of Diseases (ICD-10).                                                                                                  Source: CDC4


1 • Advances in Treatment                                                                                                                                                         5
HIV/AIDS: Decline in Death Rates
The number of U.S. AIDS deaths decreased dramatically following the introduction of highly active antiretroviral
treatment (HAART) and has continued to decline.


                                                         Annual Number of AIDS Deaths in the United States

                                18

                                16
                                     16.2
Deaths Per 100,000 Population




                                14

                                12          1996: HAART becomes widely available

                                10

                                 8

                                 6
                                                 6.0
                                                             5.3         5.0
                                 4                                                 4.7
                                                                                             4.2
                                                                                                       3.7
                                 2                                                                            3.1
                                                                                                                     2.5

                                 0
                                     1995       1997        1999        2001       2003     2005       2007   2009   2011




                                                                                                                       Source: CDC5


1 • Advances in Treatment                                                                                                        6
Cancers: Decline in Death Rates
According to the American Cancer Society, improvements in treatment contributed to the increase in cancer
survival.6


                               Percent Change by Decade in U.S. Death Rates from Cancer


          4%                4.7%
                                                3.9%



          -1%




          -6%
                                                                    -7.6%



         -11%


                                                                                          -15.5%
         -16%
                      1970–1980              1980–1990            1990–2000           2000–2011




                                                                                                      Source: CDC7


1 • Advances in Treatment                                                                                       7
Rare Diseases: Drug Approvals for Rare Diseases
Have Increased
Rare diseases are those that affect 200,000 or fewer people in the United States. There are between 6,000 and
7,000 rare diseases affecting 25 million Americans.

                                                       Number of Drug Approvals for Rare Diseases*
     450

     400

     350

     300

     250

     200
             1983: Orphan Drug Act passed
     150

     100

      50

        0


                                             Cumulative Prior Orphan Drug Approvals       New Orphan Drug Approvals



 *Approvals for rare diseases include initial approvals of new medicines and subsequent
 approvals of existing medicines for rare disease areas.                                                      Source: U.S. Food and Drug Administration (FDA)8


1 • Advances in Treatment                                                                                                                                   8
Future Impact: Need for New Treatments
for Alzheimer’s Disease
The development of a new treatment that delays the onset of Alzheimer’s could reduce Medicare and Medicaid
spending on patients with Alzheimer’s by more than $100 billion annually by 2030.*

     Projected Annual Medicare & Medicaid Spending, With and Without New Treatment Advances (Billions)**
                                                    $1,000
         Projected Medicare and Medicaid Spending




                                                     $900           Current Trajectory
                                                                    Projection with Delayed Onset Treatment Advance
                                                     $800
                                                                                                                                        $805
                                                     $700

                                                     $600
                        (in Billions)




                                                     $500                                                                $529
                                                     $400                                                                                        $443

                                                     $300
                                                                                                          $297                  $276
                                                     $200
                                                                                   $174                           $157
                                                     $100                                  $140
                                                             $122   $122
                                                       $0
                                                                2010                   2020                   2030          2040            2050

*Assumes research breakthroughs that delay the average age of onset of Alzheimer’s disease by five years beginning in 2010.
**Projected savings to Medicare and Medicaid assume research breakthroughs that slow the progression of Alzheimer’s disease.
This would dramatically reduce spending for co-morbid conditions and expensive nursing home care.                                      Source: Alzheimer’s Association9


1 • Advances in Treatment                                                                                                                                            9
Notes and Sources
1.   Executive Office of the President (EOP), President's Committee of Advisors on Science and Technology. “Report to the President
     on Propelling Innovation in Drug Discovery, Development, and Evaluation.” Washington, DC: EOP, September 2012.
2.   U.S. Department of Health and Human Services (HHS), CDC, National Center for Health Statistics (NCHS). “Health, United States,
     2008 With Chartbook.” Hyattsville, MD: HHS, 2009; 1950–2006 data from M. Heron, et al. “Deaths: Final Data for 2006.”
     National Vital Statistics Reports 2009; 57(14): 5. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf
     (accessed June 2010); 2007 data from J. Xu, et al. “Deaths: Final Data for 2007.” National Vital Statistics Reports 2010; 58(19):
     13. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_19.pdf (accessed June 2010); 2008–2009 data from K.
     Kochanek, et al. “Deaths: Preliminary Data for 2009.” National Vital Statistics Reports 2011; 59(4): 28. Hyattsville, MD: NCHS.
     www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_04.pdf (accessed August 2011); 2010–2011 data from D.L. Hoyert and J. Xu.
     “Deaths: Preliminary Data for 2011.” National Vital Statistics Reports 2012; 61(6): 5. Hyattsville, MD: NCHS.
     www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf (accessed December 2012).
3.   HHS, CDC, NCHS. “Health, United States, 2006 With Chartbook on Trends in the Health of Americans.” Hyattsville, MD: HHS,
     2006. www.cdc.gov/nchs/data/hus/hus06.pdf (accessed December 2012).
4.   CDC, NCHS, National Vital Statistics System. "Unpublished table NEWSTAN 79–98S created on 00/03/02: Age-Adjusted Death
     Rates for 72 Selected Causes by Race and Sex Using Year 2000 Standard Population: United States, 1979–98." Mortality.
     Atlanta, GA: CDC, 2002. www.cdc.gov/nchs/data/mortab/aadr7998s.pdf (accessed February 2013); D.L. Hoyert, et al. “Deaths:
     Final Data for 1999.” National Vital Statistics Reports 2001; 49(8): 1–3. Hyattsville, MD: NCHS.
     www.cdc.gov/nchs/data/nvsr/nvsr49/nvsr49_08.pdf (accessed February 2013); K.D. Kochanek, et al. “Deaths: Final Data for
     2009.” National Vital Statistics Reports 2011; 60(3): 32. Hyattsville, MD: NCHS.
     www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_03.pdf (accessed December 2012); D.L. Hoyert and J. Xu. “Deaths: Preliminary
     Data for 2011.” National Vital Statistics Reports 2012; 61(6): 28. Hyattsville, MD: NCHS.
     www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf (accessed December 2012).




1 • Advances in Treatment                                                                                                          10
Notes and Sources
5.   HHS, CDC, NCHS. “Health, United States, 2003 With Chartbook on Trends in the Health of Americans.” Hyattsville, MD: HHS,
     2003; HHS, CDC, NCHS. “Health, United States, 2009 With Chartbook on Medical Technology.” Hyattsville, MD: HHS, 2010; 2007
     data from J. Xu, K.D. Kochanek, and B. Tejada-Vera. “Deaths: Preliminary Data for 2007.” National Vital Statistics Reports 2009;
     58(1): 5. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_01.pdf (accessed December 2009); 2009 data
     from K.D. Kochanek, et al. “Deaths: Final Data for 2009.” National Vital Statistics Reports 2011; 60(3): 41. Hyattsville, MD: NCHS.
     www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_03.pdf (accessed December 2012); 2011 data from D.L. Hoyert and J. Xu. “Deaths:
     Preliminary Data for 2011.” National Vital Statistics Reports 2012; 61(6): 38. Hyattsville, MD: NCHS.
     www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf (accessed December 2012).
6.   American Cancer Society. “Cancer Facts & Figures, 2011.” Atlanta, GA: American Cancer Society, 2011.
     www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-029771.pdf (accessed
     December 2012).
7.   HHS, CDC, NCHS. “Health, United States, 2011 With Special Features on Socioeconomic Status and Health.” Hyattsville, MD:
     HHS, 2012; K.D. Kochanek, et al. “Deaths: Final Data for 2009.” National Vital Statistics Reports 2011; 60(3): 32. Hyattsville, MD:
     NCHS. www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_03.pdf (accessed December 2012); D.L. Hoyert and J. Xu. “Deaths:
     Preliminary Data for 2011.” National Vital Statistics Reports 2012; 61(6): 28. Hyattsville, MD: NCHS.
     www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf (accessed December 2012).
8.   U.S. Food and Drug Administration (FDA), Office of Orphan Product Development. “Orphan Drug Designations and Approvals
     Database.” Available at www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm (accessed December 2012).
9.   Alzheimer's Association. “Changing the Trajectory of Alzheimer's Disease: A National Imperative.” Washington, DC: Alzheimer's
     Association, May 2010.




1 • Advances in Treatment                                                                                                             11
2   RESEARCH AND
                                   DEVELOPMENT
                                   The Process of Drug Discovery and Development

                                   More than 5,000 medicines are in development globally.
                                   PhRMA member companies invested $48.5 billion in
                                   biopharmaceutical research and development (R&D) in 2012,
                                   accounting for the majority of private biopharmaceutical
                                   R&D spending. Development of new medicines is a long
                                   and high-risk process, and it has become more costly and
                                   complex over the last decade. Even among the new drug
                                   candidates reaching Phase III trials, about one-third fail.
                                   Companies “race” to bring the first medicine in a class to
                                   market, and just two in ten approved drugs are ultimately
                                   commercial successes. Recent biopharmaceutical advances
                                   — driven by scientific research and creative genius — would
                                   have been impossible without a system of laws that provide
                                   the structure, stability, and opportunity for the needed
                                   investment.




2 • Research and Development                                                                     13
Medicines in Development by Regulatory Phase Globally
In 2011, 5,408 medicines* were in clinical development worldwide.




                                                                  Phase I                      Phase II
                                                                   2,164                        2,329




                                                                              Phase III
                                        Regulatory                              833
                                         Review in
                                        the United
                                         States, 82


  *Defined as single products which are counted exactly once regardless of the number of indications pursued.   Source: Analysis Group1


2 • Research and Development                                                                                                      14
More than 900 Biologic Medicines in Development in 2013
  Biologic medicines — large, complex molecules derived from living cells — frequently represent novel strategies
  that have the potential to transform the clinical treatment of disease.

               Number of Medicines in Development in 2013, by Therapeutic Category*

             Autoimmune Disorders                             71
                     Blood Disorders                    43
                                                                                                                          A vast array of biologic
        Cancers/Related Conditions                                                                             338        medicines are in
                                                                                                                          development, for
             Cardiovascular Disease                          58                                                           example:
       Diabetes/Related Conditions                 28                                                                     • A monoclonal
                 Digestive Disorders             26                                                                           antibody to treat
                                                                                                                              juvenile rheumatoid
                      Eye Conditions            25                                                                            arthritis
                   Genetic Disorders               30                                                                     • Several cancer
                                                                                                                              vaccines for
                 Infectious Diseases                                             176                                          malignant
         Musculoskeletal Disorders                 34                                                                         melanoma
               Neurologic Disorders                  39
                                                                                                                          • A gene therapy to
                                                                                                                              treat bladder cancer
               Respiratory Disorders                38
                        Skin Diseases              30
                     Transplantation          13
                                Other                        58
                                        0           50             100     150    200    250        300        350       400
    *Some medicines are being explored in more than one therapeutic category.                                                          Source: PhRMA2
Source: Biotechnology Research Continues to Bolster Arsenal Against Disease with 633 Medicines in Development. PhRMA, 2008.

  2 • Research and Development                                                                                                                    15
Potential First-in-Class Medicines in the Pipeline
70% of drugs across the pipeline are potential first-in-class medicines.



             Percentage of Projects in Development that are Potentially First-in-Class Medicines
                                     in Selected Therapeutic Areas, 2011


              Neurology                                                                      84%

          Cardiovascular                                                                81%

                 Cancer                                                                80%

              Psychiatry                                                               79%

            Immunology                                                           72%

               Diabetes                                                       71%

               HIV/AIDS                                                      69%

              Infections                                             57%

                           0%   10%   20%     30%    40%     50%    60%    70%      80%       90%   100%


                                                                                                       Source: Analysis Group3


2 • Research and Development                                                                                             16
The Research and Development Process
Developing a new medicine takes an average of 10–15 years.




                                                             Source: PhRMA4


2 • Research and Development                                            17
Government and Industry Roles in Research & Development
Government and biopharmaceutical industry research complement one another.



                                                                          PhRMA Member Companies: $48.5 Billion




                                                                                       Clinical Research
                                                  Clinical
                                                 Research


                                              Translational
                                                Research                           Translational Research



                                                                                                Basic
                                             Basic Research                                   Research


                               National Institutes of Health: $30.9 Billion*


 *NIH spending is for FY 2012. PhRMA member companies’ spending is estimated for CY 2012.
 PhRMA member companies account for the majority of private biopharmaceutical R&D spending.
 Non-member company data are not included.                                                        Sources: PhRMA5; NIH Office of Budget6; adapted from E. Zerhouni7


2 • Research and Development                                                                                                                                   18
PhRMA Member Company R&D Spending
“The pharmaceutical industry is one of the most research-intensive industries in the United States.
Pharmaceutical firms invest as much as five times more in research and development, relative to their sales,
than the average U.S. manufacturing firm.”
                                                                      — Congressional Budget Office (CBO)8

                                                                      PhRMA Member Company R&D Expenditures: 1995–2012
                                             $60

                                                                                                                                                                       $50.7
                                                                                                                                                 $47.9 $47.4                   $48.6 $48.5*
                                             $50                                                                                                               $46.4
                                                                                                                                         $43.4
        Expenditures (Billions of Dollars)




                                                                                                                                 $39.9
                                             $40                                                                         $37.0
                                                                                                                 $34.5
                                                                                                   $29.8 $31.0
                                             $30                                           $26.0
                                                                                   $22.7
                                                                           $21.0
                                                                   $19.0
                                             $20           $16.9
                                                   $15.2


                                             $10



                                             $0
                                                   1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

 *Estimated for CY 2012.                                                                                                                                                                Source: PhRMA9


2 • Research and Development                                                                                                                                                                       19
Drug Development Costs Have Increased
According to a 2007 study, it costs an average of $1.2 billion to develop one new drug.10 More recent studies
estimate the costs to be even higher.11

              The Average Cost to Develop One New Approved Drug — Including the Cost of Failures

                                                         $1.4


                                                         $1.2
                                                                                                                                                  $1.2B
                Billions (Constant Dollars, Year 2000)




                                                         $1.0


                                                         $0.8
                                                                                                                    $800M

                                                         $0.6


                                                         $0.4

                                                                                      $320M
                                                         $0.2

                                                                 $140M
                                                         $0.0
                                                                mid-1970s           mid-1980s                    late-1990s                   early-2000s


                                                                            Sources: J.A. DiMasi and H.G. Grabowski10; J. Mestre-Ferrandiz, et al. and S.M. Paul, et al.11; J.A. DiMasi, et al.12


2 • Research and Development                                                                                                                                                                 20
Complexity of Clinical Trials Has Increased
During the last decade, clinical trial designs and procedures have become much more complex, demanding more
staff time and effort, and discouraging patient enrollment and retention.


                                                    Trends in Clinical Trial Protocol Complexity

                                                                                                                             Percentage
                                                                          2000–2003               2008–2011
                                                                                                                               Change
            Total Procedures per Trial Protocol (median)
                                                                             105.9                    166.6                        57%
           (e.g., bloodwork, routine exams, x-rays, etc.)
                        Total Investigative Site Work Burden
                                                                              28.9                     47.5                        64%
                                               (median units)
                                             Total Eligibility Criteria        31                       46                         58%
                                 Clinical Trial Treatment Period
                                                                              140                      175                         25%
                                                   (median days)*
                   Number of Case Report Form Pages per
                                                                               55                      171                        227%
                                      Protocol (median)




  *These numbers reflect only the “treatment duration” of the protocol.          Source: K.A. Getz, et al. and Tufts Center for the Study of Drug Development13


2 • Research and Development                                                                                                                               21
Illustrative Pharmaceutical Lifecycle
New pharmaceutical medicines face competition after a relatively short period on the market.




                                                     FDA                                                             Generics
                                                   Approval                                                        Enter Market
                                                                                  Most brand drugs
                                                                                   face competition
                                                                                  from other brands




                         Drug Development                                  Brand Drug Lifespan                             Generics


                      Average time to develop a                              Average time on market
                           new medicine                                       before generic entry
                            = 10–15 yrs                                            = 11.8* yrs




*Refers to new drugs (i.e., excludes new forms of administration) with annual sales in 2008 of more than $100 million,
which accounted for 95% of the sales of new medicines exposed to generic competition.                                      Sources: PhRMA14; H.G. Grabowski, et al.15



2 • Research and Development                                                                                                                                      22
Earlier and More Frequent Patent Challenges
by Generic Companies
On average, new brand drugs face generic competition after 11.8* years, but generic companies can
challenge patents as soon as 4 years after a brand enters the market.


                           Share of Brand Products that Ever Experienced a “Paragraph IV” Patent Challenge**
                           from a Generic Manufacturer, Among Those Facing Generic Entry in Year Listed

                                100%
                     Hundreds




                                80%
                                                                                                            75%
                                60%


                                40%


                                20%
                                                             17%
                                 0%
                                                             1995                                           2008
                                                                          Year of First Generic Entry

*Refers to new drugs (i.e., excludes new forms of administration) with annual sales in 2008 of more than
$100 million, which accounted for 95% of the sales of new medicines exposed to generic competition.
**A generic company may file with FDA a Paragraph IV certification to “challenge” patents associated with
brand-name medicines, potentially allowing generic market entry before the patent expiration date.                 Source: H.G. Grabowski, et al.16


2 • Research and Development                                                                                                                   23
Competing Medicines Race for Approval
By 1995, nearly all first-in-class medicines being approved already had potential competitors in
Phase II clinical testing.



                               Percentage of First-in-Class Medicines with a Competitor
                                Already in Phase II Clinical Testing at Time of Approval
          100%

           90%
                                                                                                90%
           80%

           70%                                                                 77%
                                                             71%
           60%

           50%
                                           50%
           40%

           30%

           20%
                       23%
           10%

            0%
                       1970s             1980–1984         1985–1989         1990–1994      1995–1999



                                                                                            Source: J.A. DiMasi and L.B. Faden17


2 • Research and Development                                                                                                24
Increasing Competition Within Therapeutic Categories
The time a medicine is the only drug available in its therapeutic class has declined dramatically — from a median
of more than 10 years in the 1970s to less than two years by 1998.


                                                Time Between Approval of First and Second Drugs in a Therapeutic Class
                                           12


                                           10
                                                          10.2
                  Median Number of Years




                                            8


                                            6


                                            4
                                                                                     4.1

                                            2

                                                                                                                    1.2
                                            0
                                                          1970s                     1980s                       1990–2003
                                                                  Year of Approval of First-in-Class Medicine



                                                                                                          Source: Tufts Center for the Study of Drug Development18


2 • Research and Development                                                                                                                                  25
Few Approved Medicines are Commercially Successful
    Ongoing investment in R&D depends on the commercial success of a few products that must make up for all the
    rest, including those that never reach the market.


                                            Just 2 in 10 Approved Medicines Produce Revenues that Exceed Average R&D Costs
                                   $2,000

                                            $1,880
After-Tax Present Value of Sales




                                   $1,500
   (Millions of 2000 Dollars)




                                   $1,000


                                                                                                                               After-Tax Average R&D
                                                     $701
                                    $500
                                                                $434
                                                                           $299
                                                                                                  $87
                                                                                      $162                   $39        $21
                                                                                                                                    $6              -$1
                                      $0
                                              1        2          3          4          5          6          7          8          9               10
                                                     New Medicine Introduced Between 1990 and 1994, grouped by Tenths, by Lifetime Sales



                                                                                                                                   Source: J.A. Vernon, et al.19


    2 • Research and Development                                                                                                                            26
Accounting Treatment of R&D
Overstates Biopharmaceutical Profits
“Correctly accounting for R&D as a long-lived investment tends to reduce substantially, if not to eliminate
altogether, the inference that pharmaceutical companies are on average achieving supranormal profit returns.”20
                                                 — F.M. Scherer, AEI-Brookings Joint Center for Regulatory Studies

“...the standard accounting measure of profits overstates true returns to R&D-intensive industries, such as
pharmaceuticals, and makes it difficult to meaningfully compare profit levels among industries. Accounting
measures treat most R&D spending (except for capital equipment) as a deductible business expense rather than
as a capitalized investment. But the intangible assets that research and development generate — such as
accumulated knowledge, new research capabilities, and patents — increase the value of a company’s asset base.
Not accounting for that value overstates a firm’s true return on its assets.”21
                                                                                   — Congressional Budget Office

“Usual profit figures greatly overstate the industry’s economic profit rate.”22
                                                                                  — J.P. Newhouse, Harvard University




                                                                                       Sources: F.M. Scherer20; CBO21; J.P. Newhouse22


2 • Research and Development                                                                                                      27
Notes and Sources
1.   Analysis Group. "Innovation in the Biopharmaceutical Pipeline: A Multidimensional View." Boston, MA: Analysis Group, January
     2013. www.analysisgroup.com/uploadedFiles/Publishing/Articles/2012_Innovation_in_the_Biopharmaceutical_Pipeline.pdf
     (accessed January 2013).
2.   Pharmaceutical Research and Manufacturers of America. "Medicines in Development: Biologic Medicines." Washington, DC:
     PhRMA, 2013.
3.   Analysis Group, Op. cit.
4.   Pharmaceutical Research and Manufacturers of America. "Drug Discovery and Development: Understanding the R&D Process."
     Washington, DC: PhRMA, 2007. www.innovation.org/drug_discovery/objects/pdf/RD_Brochure.pdf (accessed February 2013).
5.   Pharmaceutical Research and Manufacturers of America. “PhRMA Annual Membership Survey.” 2013.
6.   National Institutes of Health (NIH), Office of Budget. “History of Congressional Appropriations, Fiscal Years 2000–2012.”
     Bethesda, MD: NIH, 2012. http://officeofbudget.od.nih.gov/pdfs/FY12/Approp.%20History%20by%20IC)2012.pdf (accessed
     February 2013).
7.   Adapted from E. Zerhouni. “Transforming Health: NIH and the Promise of Research.” Transforming Health: Fulfilling the Promise
     of Research. Washington, DC. November 2007. Keynote address. www.researchamerica.org/transforming_health_transcript
     (accessed January 2013).
8.   CBO. “Research and Development in the Pharmaceutical Industry.” Washington, DC: CBO, October 2006.
9.   Pharmaceutical Research and Manufacturers of America. "PhRMA Annual Membership Survey." 1996–2012.
10. J.A. DiMasi and H.G. Grabowski. "The Cost of Biopharmaceutical R&D: Is Biotech Different?" Managerial and Decision
    Economics 2007; 28: 469–479.
11. More recent estimates range from $1.5 billion to more than $1.8 billion. See e.g. J. Mestre-Ferrandiz, J. Sussex, and A. Towse.
    “The R&D Cost of a New Medicine.” London, UK: Office of Health Economics, 2012; S.M. Paul, et al. “How to Improve R&D
    Productivity: The Pharmaceutical Industry’s Grand Challenge.” Nature Reviews Drug Discovery 2010; 9: 203–214.




2 • Research and Development                                                                                                          28
Notes and Sources
12.   J.A. DiMasi, et al. “The Price of Innovation: New Estimates of Drug Development Costs.” Journal of Health Economics 2003; 22:
      151–185. Study findings originally reported in 2005 dollars. Based on correspondence with the study author, these figures were
      adjusted to 2000 dollars.
13.   K.A. Getz, R.A. Campo, and K.I. Kaitin. “Variability in Protocol Design Complexity by Phase and Therapeutic Area.” Drug
      Information Journal 2011; 45(4): 413–420; updated data provided through correspondence with Tufts Center for the Study of
      Drug Development.
14.   Pharmaceutical Research and Manufacturers of America. "Drug Discovery and Development: Understanding the R&D Process."
      Washington, DC: PhRMA, 2007. www.innovation.org/drug_discovery/objects/pdf/RD_Brochure.pdf (accessed February 2013).
15.   H.G. Grabowski, et al. “Evolving Brand-name and Generic Drug Competition may Warrant a Revision of the Hatch-Waxman Act.”
      Health Affairs 2011; 30(11): 2157–2166.
16.   Estimate is based on sample of 200 New Molecular Entities (NMEs) experiencing first generic entry between 1995 and 2008.
      The 11.8 refers to the market exclusivity period, which is defined as the time between launch of the brand-name version of the
      drug and its first generic competitor. See H.G. Grabowski, et al. "Evolving Brand-name and Generic Drug Competition may
      Warrant a Revision of the Hatch-Waxman Act." Health Affairs 2011; 30(11): 2157–2166.
17.   J.A. DiMasi and L.B. Faden. "Follow-On Drug R&D: New Data on Trends in Entry Rates and the Timing of Development." Tufts
      Center for the Study of Drug Development Working Paper. Boston, MA: Tufts Center for the Study of Drug Development,
      September 2009.
18.   Tufts Center for the Study of Drug Development. Unpublished data. March 2010. Median data for shorter time periods
      published in: Tufts Center for the Study of Drug Development. “Marketing Exclusivity for First-in-Class Drugs Has Shortened to
      2.5 Years.” Impact Report 2009; 11(5).




2 • Research and Development                                                                                                       29
Notes and Sources
19. J.A. Vernon, et al. “Drug Development Costs When Financial Risk Is Measured Using the Fama-French Three-Factor Model.”
    Health Economics 2009; 19(8): 1002–1005; Drug development costs represent after-tax out-of-pocket costs in 2000 dollars for
    drugs introduced from 1990–1994. The same analysis found that the total cost of developing a new drug was $1.3 billion in
    2006. Average R&D costs include the cost of the approved medicines as well as those that fail to reach approval.
20. F.M. Scherer. “Pharmaceutical Innovation.” AEI-Brookings Joint Center for Regulatory Studies Working Paper 07–13. July 2007.
21. CBO. “Research and Development in the Pharmaceutical Industry.” Washington, DC: CBO, October 2006.
22. J.P. Newhouse. “How Much Should Medicare Pay for Drugs?” Health Affairs 2004; 23(1): 89–102.




2 • Research and Development                                                                                                   30
3   SPENDING AND COSTS
                             Biopharmaceutical Spending and Health Care Costs

                             Prescription medicines represent a small share of national
                             health spending. Since 2000, growth in prescription drug
                             spending has slowed markedly, while prices for prescription
                             medicines have risen in line with overall medical inflation.

                             Innovator pharmaceutical companies produce medical
                             advances through pioneering scientific work and large-scale
                             investments. The innovators’ work and investment lead both
                             to new medicines and, over time, to generic copies that
                             consumers use at low cost for many years.

                             Health plans use many tools — such as tiered formularies
                             and cost sharing — to steer use toward generics and lower-
                             cost medicines. Payers also typically require patients to pay
                             a higher share of the costs of medicines out-of-pocket
                             compared with other health services.




3 • Spending and Costs                                                                       32
Sharply Declining Prescription Medicine Spending
Growth: 1999–2011*
Spending growth for prescription medicines has slowed dramatically over the past decade, with historically low
rates of growth observed in recent years.


          20%

          18%
                    18.4%
          16%
                                15.4%
          14%                              14.7%
                                                      14.0%
          12%

          10%                                                  11.3%

                                                                       9.2%          9.5%
            8%

            6%                                                                6.5%

            4%                                                                              5.2%              5.0%

            2%                                                                                      2.8%                            2.9%
                                                                                                                         0.4%
            0%
                     1999       2000        2001       2002    2003    2004   2005   2006   2007    2008      2009       2010       2011


 *Total retail sales including brand medicines and generics.                                       Source: Centers for Medicare & Medicaid Services (CMS)1


3 • Spending and Costs                                                                                                                               33
Medicines Account for a Small and Declining Share of
Health Spending Growth
                Growth in Health Care Expenditures Attributable to Prescription Drugs, 1997–2011

         100%
                                                                              7%
                           17%                      13%
          90%

          80%

          70%

          60%

          50%
                                                                              93%
                           83%                      87%
          40%

          30%
                                                                                            Prescription Drugs
          20%
                                                                                            All Other Health Care

          10%

           0%
                         1997–2001                2002–2006                2007–2011

                                                                                                            Source: CMS2


3 • Spending and Costs                                                                                              34
Retail Spending on Prescription Medicines is a Small Share
of Total U.S. Health Care Spending
                                                                   Health Care Dollar, 2011



                                                                                       Prescription
                                                                                          Drugs
                                                                                          $0.10
                                                                  Other*
                                                                  $0.25


               Government                                                                         Hospital Care
            Admin. & Net Cost
                                                                                                     $0.34
             of Private Health
                 Insurance
                   $0.06
                                                                  Physician and
                      Home Health and                            Clinical Services
                     Nursing Home Care                                 $0.22
                           $0.03


*Other includes dental, home health, and other professional services as well as durable medical equipment costs.   Source: PhRMA analysis based on CMS3


3 • Spending and Costs                                                                                                                             35
Growth in Prescription Medicine Prices Has Been in Line
with Other Health Care Prices
                         Consumer Price Index (Dec 1999 = 100)
235
                                                                                        Hospital & Related Services

215


195


175
                                                                                         All Medical Costs
155                                                                                      Prescription Medicines


135                                                                                      Consumer Price Index


115


 95




                                                            Source: PhRMA analysis based on Bureau of Labor Statistics4


3 • Spending and Costs                                                                                             36
More Than Four Out of Five U.S. Prescriptions
Are Filled with Generics
                                                Generic Share* of Prescriptions Filled 1984–2012
                    90%

                    80%                                                                            84%

                    70%
                                                                                           71%
                    60%

                    50%
                                                                              52%

                    40%                                          43%

                    30%                                33%

                    20%
                                   19%
                    10%

                      0%
                                   1984                1990      1996         2002         2008    2012



  *Generic share includes generics and branded generics.                                                  Sources: IMS5,6,7,8,9


3 • Spending and Costs                                                                                                       37
The U.S. Prescription Drug Lifecycle Promotes
Innovation and Affordability
Innovator pharmaceutical companies produce medical advances through pioneering scientific work and large-
scale investments. The innovators’ work and investment lead both to new medicines and, over time, to generic
copies that consumers use at low cost for many years.

                           Daily Cost of Top 10 Therapeutic Classes* Most Commonly Used by Medicare Part D Enrollees
                           $1.50
                                   $1.50
                                                                                                                                     Actual
                                                                                                                                     Estimated
                           $1.20
                                                                                                         $1.00
        Cost per Day ($)




                           $0.90

                                                                                                                                                $0.65
                           $0.60


                           $0.30


                           $0.00



*Ten therapeutic classes most commonly used by Part D enrollees in 2006 were: lipid regulators, ACE inhibitors, calcium
channel blockers, beta blockers, proton pump inhibitors, thyroid hormone, angiotensin II, codeine and combination products,   Source: M.L. Aitken and E.R. Berndt10
antidepressants, and seizure disorder medications.


3 • Spending and Costs                                                                                                                                          38
Insurance Covers a Lower Share of Prescription
Drug Costs Than of Other Medical Services
On average, privately-insured consumers pay out-of-pocket more than 20% of their total prescription drug
spending, compared with 4% of spending for inpatient hospital care and 7% on hospital outpatient care.


                                Percentage of Spending for Each Type of Service Paid Out-of-Pocket:
                                              Privately-insured People Under Age 65
              40%



              30%



              20%                                                                                                                  22%

                                                                                                         17%

              10%
                                                                                9%
                                                      7%
                                4%
                0%
                         Hospital Inpatient   Hospital Outpatient      Emergency Room                Physicians           Prescription Drugs*


  *Includes brand & generic                                         Sources: P.J. Cunningham11; PhRMA analysis based on Medical Expenditure Panel Survey (MEPS)12


3 • Spending and Costs                                                                                                                                       39
Powerful Purchasers Negotiate on Behalf of Patients
A small number of large purchasers dominate the U.S. prescription drug market.

                           Prescription Volume by Pharmacy Benefit Management (PBM) Companies, 2012

             Company                                                    Number of Prescriptions           Market Share (%)*
             1. Express Scripts/Medco Health
                                                                                  1,411 million                  29.5%
                 Solutions**
             2. CVS/Caremark                                                       775 million                   16.2%

             3. Argus Health Systems                                               504 million                   10.5%

             4. OptumRx, Inc.                                                      319 million                    6.7%

             5. ACS, Inc.                                                          250 million                    5.2%

             Top 5 PBMs Total                                                    3,259 million                  68.2%

             Top 10 PBMs Total                                                   4,107 million                  85.9%
             Top 15 PBMs Total                                                   4,584 million                  95.9%

             All PBMs in U.S.                                                    4,780 million                   100%


*Figures may not sum to totals due to rounding.
**Medco was acquired by Express Scripts in April 2012. Figure for Express Scripts/Medco is the sum
of the individual script totals for each entity for the most recently reported 12 month period in 2012.       Source: Atlantic Information Services, Inc.13


3 • Spending and Costs                                                                                                                                 40
In the U.S. System, Health Plans Have Powerful Tools to
Reduce Spending on Medicines

                Tiered Copays                         Formularies                  Prior Authorization
            Higher cost to patients for            List of covered drugs          Physicians required to justify
           brands than for generics and                                            medicine’s use before it’s
                preferred brands                                                            covered




                                          Payers drive nearly all use of
                                           medicines to generics and
                                              “preferred” brands.


Concentrated Purchasing Power                                                        Financial Incentives
  Individual Pharmacy Benefit Managers                                             Payments to physicians and/or
    buy medicines for more people than
                                                     Step Therapy               pharmacies for generic prescribing or
       in entire European countries             Patients must try and fail on   switching patients to preferred drugs
                                                 alternatives before certain
                                                   medicines are covered


                                                                                                    Source: IMS Health, Inc.14


3 • Spending and Costs                                                                                                     41
Newly Introduced Generics are Adopted Rapidly
When a generic version of a medicine becomes available for the first time, it can capture as much as 90% of the
market within 3 months.


                      Generic Share of Filled Prescriptions Following the Launch of a New Generic Osteoporosis Treatment

                     100%
                                                                                                                     Mail
                                                                                                                     Retail

                     80%



                     60%
  Generic Use Rate




                     40%



                     20%



                      0%
                              0          7        14        30         60         90       120       150       180

                                                            Number of Days After Launch

                                                                                                            Source: Express Scripts, Inc.15


3 • Spending and Costs                                                                                                                 42
Medicines Account for a Small Share of Health Spending
Differences Between the United States and Other Countries
                    Per Capita Health Care Spending 2010, United States vs. Canada and Germany

   $9,000
                                                               $8,233
   $8,000
                                                                                                 All Other Health Care Spending
   $7,000
                                                                                                 Prescription Drugs

   $6,000

   $5,000
                         $4,445                                                                                $4,338
   $4,000

   $3,000
                                       94% of the                                    91% of the
   $2,000                                                                            difference


   $1,000

                                    6% of the difference                        9% of the difference
       $0
                         Canada                             United States                                     Germany

                                                           Source: PhRMA analysis based on Organisation for Economic Co-operation and Development16


3 • Spending and Costs                                                                                                                         43
Notes and Sources
1.   CMS. "National Health Expenditures by Type of Service and Source of Funds, CY 1960–2011." Baltimore, MD: CMS, 2012.
     www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-
     Reports/NationalHealthExpendData/NationalHealthAccountsHistorical.html (accessed January 2013).
2.   Ibid.
3.   PhRMA analysis based on CMS, “National Health Expenditures Projections 2011–2021." Baltimore, MD: CMS, 2012.
     www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-
     Reports/NationalHealthExpendData/NationalHealthAccountsProjected.html (accessed January 2013).
4.   PhRMA analysis based on U.S. Bureau of Labor Statistics (BLS). “Consumer Price Index—All Urban Consumers, History Table.”
     Washington, DC: BLS, 2012. www.bls.gov/cpi/#tables (accessed December 2012).
5.   PhRMA analysis based on IMS Health, Inc. “IMS National Prescription AuditTM.” Danbury, CT: IMS Health, 2012.
6.   IMS Health, Inc. “IMS Institute Reports U.S. Spending on Medicines Grew 2.3 Percent in 2010, to $307.4 Billion.” Danbury, CT:
     IMS Health, 2010. www.imshealth.com/portal/site/imshealth/ (accessed August 2011).
7.   PhRMA analysis based on IMS Health, Inc. “IMS National Prescription AuditTM.” Danbury, CT: IMS Health, 2011.
8.   IMS Institute for Healthcare Informatics. “The Use of Medicines in the United States: Review of 2011.” Parsippany, NJ: IMS
     Health, April 2012.
9.   IMS Health, Inc. “IMS National Prescription Audit™: December 2012.” Danbury, CT: IMS Health, 2012.
10. M.L. Aitken and E.R. Berndt. “Medicare Part D at Age Five: What Has Happened to Seniors' Prescription Drug Prices?” Parsippany,
    NJ: IMS Institute for Healthcare Informatics, July 2011.
    www.imshealth.com/ims/Global/Content/Home%20Page%20Content/IMS%20News/IHII_Medicare_Part_D2.pdf (accessed
    October 2012).
11. P.J. Cunningham. “Despite the Recession's Effects on Incomes and Jobs, the Share of People with High Medical Costs was Mostly
    Unchanged.” Health Affairs 2012; 31(11): 2563–2570.




3 • Spending and Costs                                                                                                               44
Notes and Sources
12. PhRMA analysis based on Agency for Healthcare Research and Quality (AHRQ). “Medical Expenditure Panel Survey.” Rockville,
    MD: AHRQ, 2009. www.meps.ahrq.gov/mepsweb/ (accessed December 2012). Prescription drug spending includes brand and
    generic ingredients, pharmacy, and distribution costs. Estimates are not restricted to individuals with private coverage that
    includes prescription coverage, which can be expected to account for less than 2%.
13. Atlantic Information Services, Inc. (AIS). “Pharmacy Benefit Survey Results: 4th Quarter 2012.” 2012. www.AISHealth.com
    (accessed February 2013).
14. IMS Health, Inc. “IMS National Prescription Audit™: December 2012.” Danbury, CT: IMS Health, 2004–2012.
15. Express Scripts, Inc. “2009 Drug Trend Report.” St. Louis, MO: Express Scripts, April 2010. www.express-
    scripts.com/research/research/dtr/archive/2009/dtrfinal.pdf (accessed February 2013).
16. PhRMA analysis based on Organisation for Economic Co-operation and Development (OECD). “OECD Health Data 2012—
    Frequently Requested Data.” Paris, France: OECD Publishing, June 2012.
    www.oecd.org/els/healthpoliciesanddata/oecdhealthdata2012-frequentlyrequesteddata.htm (accessed December 2012).




3 • Spending and Costs                                                                                                          45
4   OUTCOMES AND
                               SAVINGS
                               Overcoming Gaps in Treatment, Improving Outcomes, and
                               Reducing Costs through Better Use of Medicines

                               Undertreatment of chronic disease and less than optimal
                               use of prescribed medicines are significant public health
                               problems, costing the U.S. economy hundreds of billions of
                               dollars each year. Improved use of prescribed medicines,
                               however, can result in better health outcomes, lower costs
                               for other health care services, and increased worker
                               productivity.




4 • Outcomes and Savings                                                                    47
Most Americans Use Few or No Medicines — a Small Share
of People Fill the Majority of Prescriptions
The top 20% of people who used medicines accounted for almost two-thirds of all prescriptions filled in 2010.


             100%
                                     20%                                     64%
              90%

              80%
                                     80%
              70%
                                 (39% of the
                                 population
              60%                  uses no
                                 medicines)
              50%

              40%

              30%                                                            36%

              20%

              10%

               0%
                                % of Population                      % of Prescription Fills

                                                                                                        Source: MEPS1


4 • Outcomes and Savings                                                                                          48
Medicines’ Changing Role in Recommended Care
Revisions to clinical guidelines based on the latest research have resulted in appropriate increases in the use of
medicines in recent years.



            Changes in the size of the treatable population as target levels change, such as lower
            targets for blood pressure, blood glucose, lipids




            Changes in the number and type of recommended medicines — such as a shift from single
            to combination therapy — to better control conditions




            Changes in therapeutic regimen and duration to better control conditions, such as longer
            continuation of treatment for depression




                                                                                              Source: R.W. Dubois and B.B. Dean2


4 • Outcomes and Savings                                                                                                    49
Failure to Prescribe the Indicated Treatment is the
Most Common Prescribing Quality Problem
RAND researchers report that failure to prescribe an indicated treatment is a far more common quality problem
than is inappropriate medicine use.

                                                     Quality Problems Among Vulnerable Older Patients


     Failure to prescribe when called
                                                                                                                            50%
                     for by guidelines



                 Inadequate monitoring                                                                36%



                Inadequate education/
                                                                          19%
            continuity/ documentation



             Inappropriate medication                   3%


                                                0%             10%              20%             30%              40%                50%   60%
                                                                             Percentage of Quality Indicators Failed*


*Quality indicators were developed and implemented based on systematic literature reviews and multiple layers of expert judgment.           Source: RAND Health3


4 • Outcomes and Savings                                                                                                                                    50
Diabetes:
An Example of Underdiagnosis and Undertreatment
Uncontrolled diabetes can lead to kidney failure, amputation, blindness, and stroke.



                                                  26 million Americans with DIABETES




                                     19 million are DIAGNOSED                                                     7 million are UNDIAGNOSED


                              16 million are TREATED                                        3 million are
                • Blood sugar control (diet and exercise, medicines) •                      diagnosed but
                        • Testing to prevent complications •                                NOT TREATED

                                               8 million receive some treatment
  8 million are treated and have their
                                                       but their disease is
          disease CONTROLLED
                                               NOT SUCCESSFULLY CONTROLLED




           8 million have
                                                                         18 million have UNCONTROLLED diabetes
        CONTROLLED diabetes


                                                                                 Sources: CDC4; National Health and Nutrition Examination Survey (NHANES)5


4 • Outcomes and Savings                                                                                                                              51
Better Use of Medicines Improves Patient Health
Diabetes patients who take their medicines as prescribed experience fewer complications.



                       18%
                                                                                        15.9%                                  15.7%
                       16%

                       14%                                                                                                              13.0%
                                                                                                11.8%
                       12%
 Likelihood of Event




                                                                                                            10.8%
                                                                      10.1%
                       10%
                                                  8.0%                        7.8%
                       8%
                                                                                                                    5.8%
                       6%
                              4.0%                       4.0%
                       4%
                                      1.8%
                       2%

                       0%
                             Acute Myocardial   Amputation/ Ulcer    Cerebrovascular     Neuropathy         Renal Events        Retinopathy
                                Infarction                               Disease

                                                                Non-Adherent Patients   Adherent Patients



                                                                                                                           Source: T.B. Gibson, et al.6

4 • Outcomes and Savings                                                                                                                           52
Recommended Medicines Can Save Lives and Dramatically
Improve Health
“...achieving effective blood pressure control would be approximately equivalent to eliminating all deaths from
accidents, or from influenza and pneumonia combined.”
                                                                         — David Cutler, Ph.D., Harvard University



    Annual Hospitalizations and Deaths Avoided through Use of Recommended Antihypertensive Medications


                                         Annual Hospitalizations Avoided      Annual Premature Deaths Avoided


             Prevention Achieved:
                                                     833,000                                 86,000
  Based on Current Treatment Rates


    Potential Additional Prevention:
      If Untreated Patients Received                 420,000                                 89,000
           Recommended Medicines




                                                                                                   Source: D.M. Cutler, et al.7


4 • Outcomes and Savings                                                                                                   53
Prescription Medicines Are Part of the Solution to
Controlling Medical Spending
Better use of medicines reduces use of avoidable medical care, resulting in reductions in medical spending.



                                                  Adherence to Medicines Lowers Total Health Spending for Chronically Ill Patients

                                                                     Drug Spending                             Medical Spending
                                              $2,000
                                                         $1,058
                                                                    $656       $429      $601
     Difference in Annual Spending Between
      Adherent and Nonadherent Patients




                                                  $0
                                                                                                                                   -$1,860
                                              -$2,000
                                                                                                                         -$4,337
                                                                                                               -$4,413
                                              -$4,000


                                              -$6,000


                                              -$8,000                                                -$8,881


                                             -$10,000         Congestive Heart Failure    Diabetes    Hypertension       Dyslipidemia


                                                                                                                                   Source: M.C. Roebuck, et al.8


4 • Outcomes and Savings                                                                                                                                     54
Gaining Drug Coverage Reduced Other Medical Spending
 The Medicare drug benefit increased access to medicines for those previously without drug coverage, resulting
 in reduced non-drug medical spending9 and overall savings of $13.4 billion in 2007, the first full year of the
 program.10

                                            Average Reduction in Medical Spending in 2006 and 2007,
                                             for Beneficiaries Gaining Drug Coverage through Part D




                                                                                                                   Average
                                                                                                                    Total
                                                                                                                  Spending
                                                                                                                 Reduction
                                                                                                                     per
                                               -$816                                                             Beneficiary


                                                                          -$268
                                                                                                                  -$1,224

                                                                                          -$140




*Home health, durable medical equipment, hospice, and outpatient institutional services       Sources: J.M. McWilliams, et al.9; C.C. Afendulis and M.E. Chernew10



 4 • Outcomes and Savings                                                                                                                                     55
Better Use of Medicines Yields Significant Health Gains and
Savings on Other Services
In 2012, the CBO announced that its budget estimates would recognize reductions in other medical expenditures
associated with Medicare policy initiatives that increased the use of prescription medicines.11




   Numerous studies demonstrate the value of better access to and use of medicines in improving health
   outcomes and reducing use of other medical services:

   •   Better adherence to antihypertensive medications could save approximately
       200,000 lives over 5 years.12
   •   Improved medication adherence among diabetes patients could prevent
       more than 1 million emergency department visits and hospitalizations
       annually, for potential savings of $8.3 billion each year.13

   •   Non-adherence has also been linked to excess hospitalizations for conditions
       such as chronic obstructive pulmonary disease,14,15 osteoporosis,16 congestive
       heart failure, hypertension, diabetes, and dyslipidemia,17 with costs of roughly
       $170 billion per year.18



        Sources: CBO11; J.E. Bailey, et al.12; A.K. Jha, et al.13; B.C. Stuart, et al.14; L. Simoni-Wastila, et al.15 R. Halpern, et al.16; M.C. Roebuck, et al.17; and W.H. Schrank et al.18



4 • Outcomes and Savings                                                                                                                                                                 56
High Cost-Sharing Reduces Adherence
    RAND researchers found that doubling co-pays reduced patients’ adherence to prescribed medicines by 25% to
    45% and increased emergency-room visits and hospitalizations.


                                                            Percent Change in Adherence from Doubling Medicine Co-pays




                                               0%
Percent Change in Days Supplied of Medicine




                                              -5%

                                              -10%

                                              -15%

                                              -20%
                                                                                                            -26%         -26%                -25%
                                              -25%

                                              -30%                                  -33%        -32%
                                                                        -34%
                                              -35%

                                              -40%
                                                     -45%   -44%
                                              -45%

                                              -50%

                                                                                                                                Source: D.P. Goldman, et al.19


    4 • Outcomes and Savings                                                                                                                              57
New Classes of Medicines Can Improve
Adherence and Persistence
Studies have found better adherence to newer medicines.20 Similar results have been found even when insurance
requires higher patient cost-sharing for the newer medicines compared to older medicines.21


                                                      Persistence Patterns Among Antihypertensive Patients, by Drug Class
                                        60%
   Prescribed Therapy After 48 Months
   Percentage of Patients Adhering to




                                        50%
                                                                                                                                                                     51%
                                                                                                                                    47%
                                        40%
                                                                                                           41%

                                                                                 35%
                                        30%


                                        20%

                                                        16%
                                        10%


                                        0%
                                              Thiazide Diuretics (1957)   Beta Blockers (1967)   Calcium-Channel Blockers   ACE Inhibitors (1981)               ARBs (1995)
                                                                                                          (1981)

                                                                                          Drug Class (Year of First Launch22)

                                                                                                                                 Sources: P.R. Conlin, et al.20; D.A. Taira, et al.21; FDA22


4 • Outcomes and Savings                                                                                                                                                                58
Notes and Sources
 1.   IHS Global Insight Analysis based on 2010 Medical Expenditure Panel Survey (MEPS). http://meps.ahrq.gov/mepsweb/ (accessed
      December 2012).
 2.   R.W. Dubois and B.B. Dean. “Evolution of Clinical Practice Guidelines: Evidence Supporting Expanded Use of Medicines.” Disease
      Management 2006; 9(4): 210–223.
 3.   RAND Health. "U.S. Healthcare Facts About Cost, Access, and Quality." Santa Monica, CA: RAND Corporation, 2005 citing T.
      Higashi, et al. "The Quality of Pharmacologic Care for Vulnerable Older Patients." Annals of Internal Medicine 2004; 140(9): 714–
      720.
 4.   CDC. "National Diabetes Fact Sheet: National Estimates and General Information on Diabetes and Prediabetes in the United
      States, 2011." Atlanta, GA: HHS, CDC, 2011. www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf (accessed December 2012).
 5.   IHS Global Insight Analysis based on 2010 National Health and Nutrition Examination Survey (NHANES), Op. cit.
 6.   T.B. Gibson, et al. “Cost Sharing, Adherence, and Health Outcomes in Patients with Diabetes.” American Journal of Managed Care
      2010; 16(8): 589–600.
 7.   D.M. Cutler, et al. “The Value of Antihypertensive Drugs: A Perspective on Medical Innovation.” Health Affairs 2007; 26(1): 97–
      110.
 8.   M.C. Roebuck, et al. “Medication Adherence Leads to Lower Health Care Use and Costs Despite Increased Drug Spending.”
      Health Affairs 2011; 30(1): 91–99.
 9.   J.M. McWilliams, A.M. Zaslavsky, and H.A. Huskamp. “Implementation of Medicare Part D and Nondrug Medical Spending for
      Elderly Adults with Limited Prior Drug Coverage.” JAMA 2011; 306(4): 402–409.
 10. C.C. Afendulis and M.E. Chernew. “State-Level Impacts of Medicare Part D.” American Journal of Managed Care 2011; 17 Suppl
     12:S.
 11. CBO. “Offsetting Effects of Prescription Drug Use on Medicare’s Spending for Medical Service.” Washington, DC: CBO, November
     2012.
 12. J.E. Bailey, et al. “Antihypertensive Medication Adherence, Ambulatory Visits, and Risk of Stroke and Death." Journal of General
     Internal Medicine 2010; 25(6): 495–503.



4 • Outcomes and Savings                                                                                                          59
Notes and Sources
13. A.K. Jha, et al. “Greater Adherence to Diabetes Drugs is Linked to Less Hospital Use and Could Save Nearly $5 Billion Annually.”
    Health Affairs 2012; 31(8): 1836–1846.
14. B.C. Stuart, et al. “Impact of Maintenance Therapy on Hospitalization and Expenditures for Medicare Beneficiaries with Chronic
    Obstructive Pulmonary Disease.” American Journal of Geriatric Pharmacotherapy 2010; 8(5): 441–453.
15. L. Simoni-Wastila, et al. “Association of Chronic Obstructive Pulmonary Disease Maintenance Medication Adherence With All-
    Cause Hospitalization and Spending in a Medicare Population.” American Journal of Geriatric Pharmacotherapy 2012; 10(3):
    201–210.
16. R. Halpern, et al. “The Association of Adherence to Osteoporosis Therapies with Fracture, All-Cause Medical Costs, and All-
    Cause Hospitalizations: A Retrospective Claims Analysis of Female Health Plan Enrollees with Osteoporosis.” Journal of
    Managed Care Pharmacy 2011; 17(1): 25–39.
17. M.C. Roebuck, et al. “Medication Adherence Leads To Lower Health Care Use And Costs Despite Increased Drug Spending.”
    Health Affairs 2011; 30(1): 91–99.
18. W.H. Schrank, et al., "A Blueprint for Pharmacy Benefit Managers to Increase Value." American Journal of Managed Care 2009;
    15(2): 87–93.
19. D.P. Goldman, et al. “Pharmacy Benefits and the Use of Drugs by the Chronically Ill.” JAMA 2004; 291(19): 2344–2350.
20. P.R. Conlin, et al. “Four-year Persistence Patterns Among Patients Initiating Therapy with the Angiotensin II Receptor Antagonist
    Losartan Versus Other Antihypertensive Drug Classes.” Clinical Therapeutics 2001; 23(12): 1999–2010.
21. D.A. Taira, et al. “Copayment Level and Compliance with Antihypertensive Medication: Analysis and Policy Implications for
    Managed Care.” American Journal of Managed Care 2006; 12(11): 678–683.
22. U.S. Food and Drug Administration. “Drugs@FDA: FDA Approved Drug Products.”
    www.accessdata.fda.gov/scripts/cder/drugsatfda/ (accessed July 2010).




4 • Outcomes and Savings                                                                                                           60
5   MARKETING AND
                                  PROMOTION
                                  Informing Consumers and Providers about Medicines

                                  Biopharmaceutical marketing and promotion are important
                                  and extensively regulated ways of informing consumers and
                                  health care professionals about medicines.

                                  Biopharmaceutical company representatives help speed the
                                  dissemination of improvements in medical care, and many
                                  physicians value this information.

                                  Direct-to-consumer advertising (DTCA) by biopharmaceutical
                                  companies can lead patients to seek additional information
                                  and consult their doctors about previously untreated
                                  conditions; it also informs patients about medicines’ risks
                                  and benefits.

                                  While marketing and promotion increase awareness of
                                  medical treatment options, other factors, including
                                  formulary design and utilization-management strategies,
                                  often have a greater impact on prescribing decisions.




5 • Marketing and Promotion                                                                     62
Many Factors Affect Prescribing Decisions

                                Factors Influencing Prescribing Decisions in the United States in 2011

                            Clinical knowledge and experience                                84%                             13%

     Patient's particular situation, including drug interactions,
                 side effects, and contraindications
                                                                                             80%                           16%

                                     Clinical practice guidelines                    53%                       39%

                    Articles in peer-reviewed medical journals                      47%                      42%

                       Information from colleagues and peers                       40%                  49%

                   Patient's insurance coverage and formulary                      40%                 41%

   Information from pharmaceutical company representatives              18%                      51%

   Pharmaceutical company-sponsored educational programs
           featuring physician speakers, not CME
                                                                        17%                  47%

Information from insurance and prescription benefits manager
                       representatives
                                                                       15%                 40%

                                                                    A great deal    Some


                                                                                                              Source: KRC Research (survey of physicians)1



 5 • Marketing and Promotion                                                                                                                          63
Physicians Find Biopharmaceutical Representatives’
Information Up-to-date, Useful, and Reliable

                     Physicians’ Assessment of Biopharmaceutical Representatives’ Information



       Up-to-date and timely             38%                           56%                        94%




                        Useful          32%                          60%                          92%




                       Reliable       27%                        57%                              84%


                                                Strongly agree   Somewhat agree




                                                                                    Source: KRC Research (survey of physicians)2



5 • Marketing and Promotion                                                                                                  64
Advertising Often Prompts Patients to Seek
Additional Information
                     Consumer Responses to Viewing Advertisements for Prescription Medicines
  50%

  45%               47%

  40%

  35%

  30%

  25%                                         27%

  20%

  15%
                                                                     14%
  10%

   5%                                                                                                      8%

   0%
             Sought Information       Initiated Conversation    Newly Aware of                    Requested Specific
                                            with Doctor        Medical Condition                     Medication

                                                                           Source: Princeton Survey Research Associates International3



5 • Marketing and Promotion                                                                                                        65
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction
Table of Contents and Introduction

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Table of Contents and Introduction

  • 1.
  • 2.
  • 3. TABLE OF CONTENTS Introduction . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . 1 Chapter 1 Advances in Treatment . . . . . . . . . . . . . . . . . . 3 Chapter 2 Research and Development . . . . . . . . . . . . . 13 Chapter 3 Spending and Costs. . . . . . . . . . . . . . . . . . . . 32 Chapter 4 Outcomes and Savings . . . . . . . . . . . . . . . . . .47 Chapter 5 Marketing and Promotion. . . . . . . . . . . . . . . 62 Chapter 6 Economic Impact . . . . . . . . . . . . . . . . . . . . . . 73
  • 4.
  • 5. INTRODUCTION This chart pack provides facts and figures about prescription medicines and their role in the health care system. Topics include medicines’ impact on health and quality of life, the drug discovery and development process, biopharmaceutical spending and costs, the challenge of treatment gaps and improving use of prescribed therapies, the marketing and promotion of medicines, and the role of the biopharmaceutical sector in the U.S. economy. Data and information found in this publication were drawn from a wide range of sources, including government agency reports, peer-reviewed journals, and the Pharmaceutical Research and Manufacturers of America’s (PhRMA’s) own research and analysis. PhRMA hopes this publication provides useful context for discussions about the role of medicines in the U.S. health care system. 1
  • 7. 1 ADVANCES IN TREATMENT Medicines’ Impact on Health and Quality of Life Prescription medicines play a large role in saving and improving lives. Over the last 25 years, prescription medicines have significantly reduced deaths from major diseases such as heart disease, several cancers, and HIV/AIDS. They have also improved the quality of life for people suffering from conditions such as arthritis and Alzheimer’s disease. Recent advances have included, for example, entirely new classes of treatments for diabetes, hypertension, and HIV/AIDS; a new generation of personalized medicines; and the very first treatments for a number of rare diseases, such as Pompe disease and Hunter syndrome. As our population ages and faces increased rates of disease, medical advances will be key to alleviating suffering. 1 • Advances in Treatment 3
  • 8. U.S. Life Expectancy 1950–2011* “While nutrition, sanitation, other public health measures, and expanded access to care have been major sources of increasing human health, innovative medicines have also played a profound role in this progress.” — The President’s Committee of Advisors on Science and Technology1 85 81.1 78.8 79.3 80 77.4 76.3 At Birth (in Years) 74.7 74.1 75 73.1 71.8 71.1 70 70 66.6 67.1 65.6 65 Women Men 60 1950 1960 1970 1980 1990 2000 2011 *Life expectancies prior to 1997 were calculated using a slightly different methodology than for those post-1997. Source: U.S. Centers for Disease Control and Prevention (CDC)2 1 • Advances in Treatment 4
  • 9. Cardiovascular Disease: Declining Rates of Death and Heart Failure “Factors contributing to the decline in heart disease and stroke mortality include better control of risk factors, improved access to early detection, and better treatment and care, including new drugs and expanded uses for existing drugs.” — U.S. Centers for Disease Control and Prevention3 U.S. Death Rates Due to Diseases of the Heart* 450 401.6 397.0 388.9 375.0 Age-adjusted Death Rates per 100,000 400 355.9 332.0 350 313.8 309.9 296.3 300 280.4 266.5 247.8 232.3 250 211.1 190.9 180.1 200 173.7 150 100 50 0 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 *Age-adjusted death rates based on Year 2000 U.S. Standard Population. 1980–1998 causes of death are classified by the Ninth Revision International Classification of Diseases (ICD-9). Beginning in 1999, causes of death are classified by the Tenth Revision International Classification of Diseases (ICD-10). Source: CDC4 1 • Advances in Treatment 5
  • 10. HIV/AIDS: Decline in Death Rates The number of U.S. AIDS deaths decreased dramatically following the introduction of highly active antiretroviral treatment (HAART) and has continued to decline. Annual Number of AIDS Deaths in the United States 18 16 16.2 Deaths Per 100,000 Population 14 12 1996: HAART becomes widely available 10 8 6 6.0 5.3 5.0 4 4.7 4.2 3.7 2 3.1 2.5 0 1995 1997 1999 2001 2003 2005 2007 2009 2011 Source: CDC5 1 • Advances in Treatment 6
  • 11. Cancers: Decline in Death Rates According to the American Cancer Society, improvements in treatment contributed to the increase in cancer survival.6 Percent Change by Decade in U.S. Death Rates from Cancer 4% 4.7% 3.9% -1% -6% -7.6% -11% -15.5% -16% 1970–1980 1980–1990 1990–2000 2000–2011 Source: CDC7 1 • Advances in Treatment 7
  • 12. Rare Diseases: Drug Approvals for Rare Diseases Have Increased Rare diseases are those that affect 200,000 or fewer people in the United States. There are between 6,000 and 7,000 rare diseases affecting 25 million Americans. Number of Drug Approvals for Rare Diseases* 450 400 350 300 250 200 1983: Orphan Drug Act passed 150 100 50 0 Cumulative Prior Orphan Drug Approvals New Orphan Drug Approvals *Approvals for rare diseases include initial approvals of new medicines and subsequent approvals of existing medicines for rare disease areas. Source: U.S. Food and Drug Administration (FDA)8 1 • Advances in Treatment 8
  • 13. Future Impact: Need for New Treatments for Alzheimer’s Disease The development of a new treatment that delays the onset of Alzheimer’s could reduce Medicare and Medicaid spending on patients with Alzheimer’s by more than $100 billion annually by 2030.* Projected Annual Medicare & Medicaid Spending, With and Without New Treatment Advances (Billions)** $1,000 Projected Medicare and Medicaid Spending $900 Current Trajectory Projection with Delayed Onset Treatment Advance $800 $805 $700 $600 (in Billions) $500 $529 $400 $443 $300 $297 $276 $200 $174 $157 $100 $140 $122 $122 $0 2010 2020 2030 2040 2050 *Assumes research breakthroughs that delay the average age of onset of Alzheimer’s disease by five years beginning in 2010. **Projected savings to Medicare and Medicaid assume research breakthroughs that slow the progression of Alzheimer’s disease. This would dramatically reduce spending for co-morbid conditions and expensive nursing home care. Source: Alzheimer’s Association9 1 • Advances in Treatment 9
  • 14. Notes and Sources 1. Executive Office of the President (EOP), President's Committee of Advisors on Science and Technology. “Report to the President on Propelling Innovation in Drug Discovery, Development, and Evaluation.” Washington, DC: EOP, September 2012. 2. U.S. Department of Health and Human Services (HHS), CDC, National Center for Health Statistics (NCHS). “Health, United States, 2008 With Chartbook.” Hyattsville, MD: HHS, 2009; 1950–2006 data from M. Heron, et al. “Deaths: Final Data for 2006.” National Vital Statistics Reports 2009; 57(14): 5. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf (accessed June 2010); 2007 data from J. Xu, et al. “Deaths: Final Data for 2007.” National Vital Statistics Reports 2010; 58(19): 13. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_19.pdf (accessed June 2010); 2008–2009 data from K. Kochanek, et al. “Deaths: Preliminary Data for 2009.” National Vital Statistics Reports 2011; 59(4): 28. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_04.pdf (accessed August 2011); 2010–2011 data from D.L. Hoyert and J. Xu. “Deaths: Preliminary Data for 2011.” National Vital Statistics Reports 2012; 61(6): 5. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf (accessed December 2012). 3. HHS, CDC, NCHS. “Health, United States, 2006 With Chartbook on Trends in the Health of Americans.” Hyattsville, MD: HHS, 2006. www.cdc.gov/nchs/data/hus/hus06.pdf (accessed December 2012). 4. CDC, NCHS, National Vital Statistics System. "Unpublished table NEWSTAN 79–98S created on 00/03/02: Age-Adjusted Death Rates for 72 Selected Causes by Race and Sex Using Year 2000 Standard Population: United States, 1979–98." Mortality. Atlanta, GA: CDC, 2002. www.cdc.gov/nchs/data/mortab/aadr7998s.pdf (accessed February 2013); D.L. Hoyert, et al. “Deaths: Final Data for 1999.” National Vital Statistics Reports 2001; 49(8): 1–3. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr49/nvsr49_08.pdf (accessed February 2013); K.D. Kochanek, et al. “Deaths: Final Data for 2009.” National Vital Statistics Reports 2011; 60(3): 32. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_03.pdf (accessed December 2012); D.L. Hoyert and J. Xu. “Deaths: Preliminary Data for 2011.” National Vital Statistics Reports 2012; 61(6): 28. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf (accessed December 2012). 1 • Advances in Treatment 10
  • 15. Notes and Sources 5. HHS, CDC, NCHS. “Health, United States, 2003 With Chartbook on Trends in the Health of Americans.” Hyattsville, MD: HHS, 2003; HHS, CDC, NCHS. “Health, United States, 2009 With Chartbook on Medical Technology.” Hyattsville, MD: HHS, 2010; 2007 data from J. Xu, K.D. Kochanek, and B. Tejada-Vera. “Deaths: Preliminary Data for 2007.” National Vital Statistics Reports 2009; 58(1): 5. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_01.pdf (accessed December 2009); 2009 data from K.D. Kochanek, et al. “Deaths: Final Data for 2009.” National Vital Statistics Reports 2011; 60(3): 41. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_03.pdf (accessed December 2012); 2011 data from D.L. Hoyert and J. Xu. “Deaths: Preliminary Data for 2011.” National Vital Statistics Reports 2012; 61(6): 38. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf (accessed December 2012). 6. American Cancer Society. “Cancer Facts & Figures, 2011.” Atlanta, GA: American Cancer Society, 2011. www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-029771.pdf (accessed December 2012). 7. HHS, CDC, NCHS. “Health, United States, 2011 With Special Features on Socioeconomic Status and Health.” Hyattsville, MD: HHS, 2012; K.D. Kochanek, et al. “Deaths: Final Data for 2009.” National Vital Statistics Reports 2011; 60(3): 32. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_03.pdf (accessed December 2012); D.L. Hoyert and J. Xu. “Deaths: Preliminary Data for 2011.” National Vital Statistics Reports 2012; 61(6): 28. Hyattsville, MD: NCHS. www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf (accessed December 2012). 8. U.S. Food and Drug Administration (FDA), Office of Orphan Product Development. “Orphan Drug Designations and Approvals Database.” Available at www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm (accessed December 2012). 9. Alzheimer's Association. “Changing the Trajectory of Alzheimer's Disease: A National Imperative.” Washington, DC: Alzheimer's Association, May 2010. 1 • Advances in Treatment 11
  • 16.
  • 17. 2 RESEARCH AND DEVELOPMENT The Process of Drug Discovery and Development More than 5,000 medicines are in development globally. PhRMA member companies invested $48.5 billion in biopharmaceutical research and development (R&D) in 2012, accounting for the majority of private biopharmaceutical R&D spending. Development of new medicines is a long and high-risk process, and it has become more costly and complex over the last decade. Even among the new drug candidates reaching Phase III trials, about one-third fail. Companies “race” to bring the first medicine in a class to market, and just two in ten approved drugs are ultimately commercial successes. Recent biopharmaceutical advances — driven by scientific research and creative genius — would have been impossible without a system of laws that provide the structure, stability, and opportunity for the needed investment. 2 • Research and Development 13
  • 18. Medicines in Development by Regulatory Phase Globally In 2011, 5,408 medicines* were in clinical development worldwide. Phase I Phase II 2,164 2,329 Phase III Regulatory 833 Review in the United States, 82 *Defined as single products which are counted exactly once regardless of the number of indications pursued. Source: Analysis Group1 2 • Research and Development 14
  • 19. More than 900 Biologic Medicines in Development in 2013 Biologic medicines — large, complex molecules derived from living cells — frequently represent novel strategies that have the potential to transform the clinical treatment of disease. Number of Medicines in Development in 2013, by Therapeutic Category* Autoimmune Disorders 71 Blood Disorders 43 A vast array of biologic Cancers/Related Conditions 338 medicines are in development, for Cardiovascular Disease 58 example: Diabetes/Related Conditions 28 • A monoclonal Digestive Disorders 26 antibody to treat juvenile rheumatoid Eye Conditions 25 arthritis Genetic Disorders 30 • Several cancer vaccines for Infectious Diseases 176 malignant Musculoskeletal Disorders 34 melanoma Neurologic Disorders 39 • A gene therapy to treat bladder cancer Respiratory Disorders 38 Skin Diseases 30 Transplantation 13 Other 58 0 50 100 150 200 250 300 350 400 *Some medicines are being explored in more than one therapeutic category. Source: PhRMA2 Source: Biotechnology Research Continues to Bolster Arsenal Against Disease with 633 Medicines in Development. PhRMA, 2008. 2 • Research and Development 15
  • 20. Potential First-in-Class Medicines in the Pipeline 70% of drugs across the pipeline are potential first-in-class medicines. Percentage of Projects in Development that are Potentially First-in-Class Medicines in Selected Therapeutic Areas, 2011 Neurology 84% Cardiovascular 81% Cancer 80% Psychiatry 79% Immunology 72% Diabetes 71% HIV/AIDS 69% Infections 57% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Source: Analysis Group3 2 • Research and Development 16
  • 21. The Research and Development Process Developing a new medicine takes an average of 10–15 years. Source: PhRMA4 2 • Research and Development 17
  • 22. Government and Industry Roles in Research & Development Government and biopharmaceutical industry research complement one another. PhRMA Member Companies: $48.5 Billion Clinical Research Clinical Research Translational Research Translational Research Basic Basic Research Research National Institutes of Health: $30.9 Billion* *NIH spending is for FY 2012. PhRMA member companies’ spending is estimated for CY 2012. PhRMA member companies account for the majority of private biopharmaceutical R&D spending. Non-member company data are not included. Sources: PhRMA5; NIH Office of Budget6; adapted from E. Zerhouni7 2 • Research and Development 18
  • 23. PhRMA Member Company R&D Spending “The pharmaceutical industry is one of the most research-intensive industries in the United States. Pharmaceutical firms invest as much as five times more in research and development, relative to their sales, than the average U.S. manufacturing firm.” — Congressional Budget Office (CBO)8 PhRMA Member Company R&D Expenditures: 1995–2012 $60 $50.7 $47.9 $47.4 $48.6 $48.5* $50 $46.4 $43.4 Expenditures (Billions of Dollars) $39.9 $40 $37.0 $34.5 $29.8 $31.0 $30 $26.0 $22.7 $21.0 $19.0 $20 $16.9 $15.2 $10 $0 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 *Estimated for CY 2012. Source: PhRMA9 2 • Research and Development 19
  • 24. Drug Development Costs Have Increased According to a 2007 study, it costs an average of $1.2 billion to develop one new drug.10 More recent studies estimate the costs to be even higher.11 The Average Cost to Develop One New Approved Drug — Including the Cost of Failures $1.4 $1.2 $1.2B Billions (Constant Dollars, Year 2000) $1.0 $0.8 $800M $0.6 $0.4 $320M $0.2 $140M $0.0 mid-1970s mid-1980s late-1990s early-2000s Sources: J.A. DiMasi and H.G. Grabowski10; J. Mestre-Ferrandiz, et al. and S.M. Paul, et al.11; J.A. DiMasi, et al.12 2 • Research and Development 20
  • 25. Complexity of Clinical Trials Has Increased During the last decade, clinical trial designs and procedures have become much more complex, demanding more staff time and effort, and discouraging patient enrollment and retention. Trends in Clinical Trial Protocol Complexity Percentage 2000–2003 2008–2011 Change Total Procedures per Trial Protocol (median) 105.9 166.6 57% (e.g., bloodwork, routine exams, x-rays, etc.) Total Investigative Site Work Burden 28.9 47.5 64% (median units) Total Eligibility Criteria 31 46 58% Clinical Trial Treatment Period 140 175 25% (median days)* Number of Case Report Form Pages per 55 171 227% Protocol (median) *These numbers reflect only the “treatment duration” of the protocol. Source: K.A. Getz, et al. and Tufts Center for the Study of Drug Development13 2 • Research and Development 21
  • 26. Illustrative Pharmaceutical Lifecycle New pharmaceutical medicines face competition after a relatively short period on the market. FDA Generics Approval Enter Market Most brand drugs face competition from other brands Drug Development Brand Drug Lifespan Generics Average time to develop a Average time on market new medicine before generic entry = 10–15 yrs = 11.8* yrs *Refers to new drugs (i.e., excludes new forms of administration) with annual sales in 2008 of more than $100 million, which accounted for 95% of the sales of new medicines exposed to generic competition. Sources: PhRMA14; H.G. Grabowski, et al.15 2 • Research and Development 22
  • 27. Earlier and More Frequent Patent Challenges by Generic Companies On average, new brand drugs face generic competition after 11.8* years, but generic companies can challenge patents as soon as 4 years after a brand enters the market. Share of Brand Products that Ever Experienced a “Paragraph IV” Patent Challenge** from a Generic Manufacturer, Among Those Facing Generic Entry in Year Listed 100% Hundreds 80% 75% 60% 40% 20% 17% 0% 1995 2008 Year of First Generic Entry *Refers to new drugs (i.e., excludes new forms of administration) with annual sales in 2008 of more than $100 million, which accounted for 95% of the sales of new medicines exposed to generic competition. **A generic company may file with FDA a Paragraph IV certification to “challenge” patents associated with brand-name medicines, potentially allowing generic market entry before the patent expiration date. Source: H.G. Grabowski, et al.16 2 • Research and Development 23
  • 28. Competing Medicines Race for Approval By 1995, nearly all first-in-class medicines being approved already had potential competitors in Phase II clinical testing. Percentage of First-in-Class Medicines with a Competitor Already in Phase II Clinical Testing at Time of Approval 100% 90% 90% 80% 70% 77% 71% 60% 50% 50% 40% 30% 20% 23% 10% 0% 1970s 1980–1984 1985–1989 1990–1994 1995–1999 Source: J.A. DiMasi and L.B. Faden17 2 • Research and Development 24
  • 29. Increasing Competition Within Therapeutic Categories The time a medicine is the only drug available in its therapeutic class has declined dramatically — from a median of more than 10 years in the 1970s to less than two years by 1998. Time Between Approval of First and Second Drugs in a Therapeutic Class 12 10 10.2 Median Number of Years 8 6 4 4.1 2 1.2 0 1970s 1980s 1990–2003 Year of Approval of First-in-Class Medicine Source: Tufts Center for the Study of Drug Development18 2 • Research and Development 25
  • 30. Few Approved Medicines are Commercially Successful Ongoing investment in R&D depends on the commercial success of a few products that must make up for all the rest, including those that never reach the market. Just 2 in 10 Approved Medicines Produce Revenues that Exceed Average R&D Costs $2,000 $1,880 After-Tax Present Value of Sales $1,500 (Millions of 2000 Dollars) $1,000 After-Tax Average R&D $701 $500 $434 $299 $87 $162 $39 $21 $6 -$1 $0 1 2 3 4 5 6 7 8 9 10 New Medicine Introduced Between 1990 and 1994, grouped by Tenths, by Lifetime Sales Source: J.A. Vernon, et al.19 2 • Research and Development 26
  • 31. Accounting Treatment of R&D Overstates Biopharmaceutical Profits “Correctly accounting for R&D as a long-lived investment tends to reduce substantially, if not to eliminate altogether, the inference that pharmaceutical companies are on average achieving supranormal profit returns.”20 — F.M. Scherer, AEI-Brookings Joint Center for Regulatory Studies “...the standard accounting measure of profits overstates true returns to R&D-intensive industries, such as pharmaceuticals, and makes it difficult to meaningfully compare profit levels among industries. Accounting measures treat most R&D spending (except for capital equipment) as a deductible business expense rather than as a capitalized investment. But the intangible assets that research and development generate — such as accumulated knowledge, new research capabilities, and patents — increase the value of a company’s asset base. Not accounting for that value overstates a firm’s true return on its assets.”21 — Congressional Budget Office “Usual profit figures greatly overstate the industry’s economic profit rate.”22 — J.P. Newhouse, Harvard University Sources: F.M. Scherer20; CBO21; J.P. Newhouse22 2 • Research and Development 27
  • 32. Notes and Sources 1. Analysis Group. "Innovation in the Biopharmaceutical Pipeline: A Multidimensional View." Boston, MA: Analysis Group, January 2013. www.analysisgroup.com/uploadedFiles/Publishing/Articles/2012_Innovation_in_the_Biopharmaceutical_Pipeline.pdf (accessed January 2013). 2. Pharmaceutical Research and Manufacturers of America. "Medicines in Development: Biologic Medicines." Washington, DC: PhRMA, 2013. 3. Analysis Group, Op. cit. 4. Pharmaceutical Research and Manufacturers of America. "Drug Discovery and Development: Understanding the R&D Process." Washington, DC: PhRMA, 2007. www.innovation.org/drug_discovery/objects/pdf/RD_Brochure.pdf (accessed February 2013). 5. Pharmaceutical Research and Manufacturers of America. “PhRMA Annual Membership Survey.” 2013. 6. National Institutes of Health (NIH), Office of Budget. “History of Congressional Appropriations, Fiscal Years 2000–2012.” Bethesda, MD: NIH, 2012. http://officeofbudget.od.nih.gov/pdfs/FY12/Approp.%20History%20by%20IC)2012.pdf (accessed February 2013). 7. Adapted from E. Zerhouni. “Transforming Health: NIH and the Promise of Research.” Transforming Health: Fulfilling the Promise of Research. Washington, DC. November 2007. Keynote address. www.researchamerica.org/transforming_health_transcript (accessed January 2013). 8. CBO. “Research and Development in the Pharmaceutical Industry.” Washington, DC: CBO, October 2006. 9. Pharmaceutical Research and Manufacturers of America. "PhRMA Annual Membership Survey." 1996–2012. 10. J.A. DiMasi and H.G. Grabowski. "The Cost of Biopharmaceutical R&D: Is Biotech Different?" Managerial and Decision Economics 2007; 28: 469–479. 11. More recent estimates range from $1.5 billion to more than $1.8 billion. See e.g. J. Mestre-Ferrandiz, J. Sussex, and A. Towse. “The R&D Cost of a New Medicine.” London, UK: Office of Health Economics, 2012; S.M. Paul, et al. “How to Improve R&D Productivity: The Pharmaceutical Industry’s Grand Challenge.” Nature Reviews Drug Discovery 2010; 9: 203–214. 2 • Research and Development 28
  • 33. Notes and Sources 12. J.A. DiMasi, et al. “The Price of Innovation: New Estimates of Drug Development Costs.” Journal of Health Economics 2003; 22: 151–185. Study findings originally reported in 2005 dollars. Based on correspondence with the study author, these figures were adjusted to 2000 dollars. 13. K.A. Getz, R.A. Campo, and K.I. Kaitin. “Variability in Protocol Design Complexity by Phase and Therapeutic Area.” Drug Information Journal 2011; 45(4): 413–420; updated data provided through correspondence with Tufts Center for the Study of Drug Development. 14. Pharmaceutical Research and Manufacturers of America. "Drug Discovery and Development: Understanding the R&D Process." Washington, DC: PhRMA, 2007. www.innovation.org/drug_discovery/objects/pdf/RD_Brochure.pdf (accessed February 2013). 15. H.G. Grabowski, et al. “Evolving Brand-name and Generic Drug Competition may Warrant a Revision of the Hatch-Waxman Act.” Health Affairs 2011; 30(11): 2157–2166. 16. Estimate is based on sample of 200 New Molecular Entities (NMEs) experiencing first generic entry between 1995 and 2008. The 11.8 refers to the market exclusivity period, which is defined as the time between launch of the brand-name version of the drug and its first generic competitor. See H.G. Grabowski, et al. "Evolving Brand-name and Generic Drug Competition may Warrant a Revision of the Hatch-Waxman Act." Health Affairs 2011; 30(11): 2157–2166. 17. J.A. DiMasi and L.B. Faden. "Follow-On Drug R&D: New Data on Trends in Entry Rates and the Timing of Development." Tufts Center for the Study of Drug Development Working Paper. Boston, MA: Tufts Center for the Study of Drug Development, September 2009. 18. Tufts Center for the Study of Drug Development. Unpublished data. March 2010. Median data for shorter time periods published in: Tufts Center for the Study of Drug Development. “Marketing Exclusivity for First-in-Class Drugs Has Shortened to 2.5 Years.” Impact Report 2009; 11(5). 2 • Research and Development 29
  • 34. Notes and Sources 19. J.A. Vernon, et al. “Drug Development Costs When Financial Risk Is Measured Using the Fama-French Three-Factor Model.” Health Economics 2009; 19(8): 1002–1005; Drug development costs represent after-tax out-of-pocket costs in 2000 dollars for drugs introduced from 1990–1994. The same analysis found that the total cost of developing a new drug was $1.3 billion in 2006. Average R&D costs include the cost of the approved medicines as well as those that fail to reach approval. 20. F.M. Scherer. “Pharmaceutical Innovation.” AEI-Brookings Joint Center for Regulatory Studies Working Paper 07–13. July 2007. 21. CBO. “Research and Development in the Pharmaceutical Industry.” Washington, DC: CBO, October 2006. 22. J.P. Newhouse. “How Much Should Medicare Pay for Drugs?” Health Affairs 2004; 23(1): 89–102. 2 • Research and Development 30
  • 35.
  • 36. 3 SPENDING AND COSTS Biopharmaceutical Spending and Health Care Costs Prescription medicines represent a small share of national health spending. Since 2000, growth in prescription drug spending has slowed markedly, while prices for prescription medicines have risen in line with overall medical inflation. Innovator pharmaceutical companies produce medical advances through pioneering scientific work and large-scale investments. The innovators’ work and investment lead both to new medicines and, over time, to generic copies that consumers use at low cost for many years. Health plans use many tools — such as tiered formularies and cost sharing — to steer use toward generics and lower- cost medicines. Payers also typically require patients to pay a higher share of the costs of medicines out-of-pocket compared with other health services. 3 • Spending and Costs 32
  • 37. Sharply Declining Prescription Medicine Spending Growth: 1999–2011* Spending growth for prescription medicines has slowed dramatically over the past decade, with historically low rates of growth observed in recent years. 20% 18% 18.4% 16% 15.4% 14% 14.7% 14.0% 12% 10% 11.3% 9.2% 9.5% 8% 6% 6.5% 4% 5.2% 5.0% 2% 2.8% 2.9% 0.4% 0% 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 *Total retail sales including brand medicines and generics. Source: Centers for Medicare & Medicaid Services (CMS)1 3 • Spending and Costs 33
  • 38. Medicines Account for a Small and Declining Share of Health Spending Growth Growth in Health Care Expenditures Attributable to Prescription Drugs, 1997–2011 100% 7% 17% 13% 90% 80% 70% 60% 50% 93% 83% 87% 40% 30% Prescription Drugs 20% All Other Health Care 10% 0% 1997–2001 2002–2006 2007–2011 Source: CMS2 3 • Spending and Costs 34
  • 39. Retail Spending on Prescription Medicines is a Small Share of Total U.S. Health Care Spending Health Care Dollar, 2011 Prescription Drugs $0.10 Other* $0.25 Government Hospital Care Admin. & Net Cost $0.34 of Private Health Insurance $0.06 Physician and Home Health and Clinical Services Nursing Home Care $0.22 $0.03 *Other includes dental, home health, and other professional services as well as durable medical equipment costs. Source: PhRMA analysis based on CMS3 3 • Spending and Costs 35
  • 40. Growth in Prescription Medicine Prices Has Been in Line with Other Health Care Prices Consumer Price Index (Dec 1999 = 100) 235 Hospital & Related Services 215 195 175 All Medical Costs 155 Prescription Medicines 135 Consumer Price Index 115 95 Source: PhRMA analysis based on Bureau of Labor Statistics4 3 • Spending and Costs 36
  • 41. More Than Four Out of Five U.S. Prescriptions Are Filled with Generics Generic Share* of Prescriptions Filled 1984–2012 90% 80% 84% 70% 71% 60% 50% 52% 40% 43% 30% 33% 20% 19% 10% 0% 1984 1990 1996 2002 2008 2012 *Generic share includes generics and branded generics. Sources: IMS5,6,7,8,9 3 • Spending and Costs 37
  • 42. The U.S. Prescription Drug Lifecycle Promotes Innovation and Affordability Innovator pharmaceutical companies produce medical advances through pioneering scientific work and large- scale investments. The innovators’ work and investment lead both to new medicines and, over time, to generic copies that consumers use at low cost for many years. Daily Cost of Top 10 Therapeutic Classes* Most Commonly Used by Medicare Part D Enrollees $1.50 $1.50 Actual Estimated $1.20 $1.00 Cost per Day ($) $0.90 $0.65 $0.60 $0.30 $0.00 *Ten therapeutic classes most commonly used by Part D enrollees in 2006 were: lipid regulators, ACE inhibitors, calcium channel blockers, beta blockers, proton pump inhibitors, thyroid hormone, angiotensin II, codeine and combination products, Source: M.L. Aitken and E.R. Berndt10 antidepressants, and seizure disorder medications. 3 • Spending and Costs 38
  • 43. Insurance Covers a Lower Share of Prescription Drug Costs Than of Other Medical Services On average, privately-insured consumers pay out-of-pocket more than 20% of their total prescription drug spending, compared with 4% of spending for inpatient hospital care and 7% on hospital outpatient care. Percentage of Spending for Each Type of Service Paid Out-of-Pocket: Privately-insured People Under Age 65 40% 30% 20% 22% 17% 10% 9% 7% 4% 0% Hospital Inpatient Hospital Outpatient Emergency Room Physicians Prescription Drugs* *Includes brand & generic Sources: P.J. Cunningham11; PhRMA analysis based on Medical Expenditure Panel Survey (MEPS)12 3 • Spending and Costs 39
  • 44. Powerful Purchasers Negotiate on Behalf of Patients A small number of large purchasers dominate the U.S. prescription drug market. Prescription Volume by Pharmacy Benefit Management (PBM) Companies, 2012 Company Number of Prescriptions Market Share (%)* 1. Express Scripts/Medco Health 1,411 million 29.5% Solutions** 2. CVS/Caremark 775 million 16.2% 3. Argus Health Systems 504 million 10.5% 4. OptumRx, Inc. 319 million 6.7% 5. ACS, Inc. 250 million 5.2% Top 5 PBMs Total 3,259 million 68.2% Top 10 PBMs Total 4,107 million 85.9% Top 15 PBMs Total 4,584 million 95.9% All PBMs in U.S. 4,780 million 100% *Figures may not sum to totals due to rounding. **Medco was acquired by Express Scripts in April 2012. Figure for Express Scripts/Medco is the sum of the individual script totals for each entity for the most recently reported 12 month period in 2012. Source: Atlantic Information Services, Inc.13 3 • Spending and Costs 40
  • 45. In the U.S. System, Health Plans Have Powerful Tools to Reduce Spending on Medicines Tiered Copays Formularies Prior Authorization Higher cost to patients for List of covered drugs Physicians required to justify brands than for generics and medicine’s use before it’s preferred brands covered Payers drive nearly all use of medicines to generics and “preferred” brands. Concentrated Purchasing Power Financial Incentives Individual Pharmacy Benefit Managers Payments to physicians and/or buy medicines for more people than Step Therapy pharmacies for generic prescribing or in entire European countries Patients must try and fail on switching patients to preferred drugs alternatives before certain medicines are covered Source: IMS Health, Inc.14 3 • Spending and Costs 41
  • 46. Newly Introduced Generics are Adopted Rapidly When a generic version of a medicine becomes available for the first time, it can capture as much as 90% of the market within 3 months. Generic Share of Filled Prescriptions Following the Launch of a New Generic Osteoporosis Treatment 100% Mail Retail 80% 60% Generic Use Rate 40% 20% 0% 0 7 14 30 60 90 120 150 180 Number of Days After Launch Source: Express Scripts, Inc.15 3 • Spending and Costs 42
  • 47. Medicines Account for a Small Share of Health Spending Differences Between the United States and Other Countries Per Capita Health Care Spending 2010, United States vs. Canada and Germany $9,000 $8,233 $8,000 All Other Health Care Spending $7,000 Prescription Drugs $6,000 $5,000 $4,445 $4,338 $4,000 $3,000 94% of the 91% of the $2,000 difference $1,000 6% of the difference 9% of the difference $0 Canada United States Germany Source: PhRMA analysis based on Organisation for Economic Co-operation and Development16 3 • Spending and Costs 43
  • 48. Notes and Sources 1. CMS. "National Health Expenditures by Type of Service and Source of Funds, CY 1960–2011." Baltimore, MD: CMS, 2012. www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and- Reports/NationalHealthExpendData/NationalHealthAccountsHistorical.html (accessed January 2013). 2. Ibid. 3. PhRMA analysis based on CMS, “National Health Expenditures Projections 2011–2021." Baltimore, MD: CMS, 2012. www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and- Reports/NationalHealthExpendData/NationalHealthAccountsProjected.html (accessed January 2013). 4. PhRMA analysis based on U.S. Bureau of Labor Statistics (BLS). “Consumer Price Index—All Urban Consumers, History Table.” Washington, DC: BLS, 2012. www.bls.gov/cpi/#tables (accessed December 2012). 5. PhRMA analysis based on IMS Health, Inc. “IMS National Prescription AuditTM.” Danbury, CT: IMS Health, 2012. 6. IMS Health, Inc. “IMS Institute Reports U.S. Spending on Medicines Grew 2.3 Percent in 2010, to $307.4 Billion.” Danbury, CT: IMS Health, 2010. www.imshealth.com/portal/site/imshealth/ (accessed August 2011). 7. PhRMA analysis based on IMS Health, Inc. “IMS National Prescription AuditTM.” Danbury, CT: IMS Health, 2011. 8. IMS Institute for Healthcare Informatics. “The Use of Medicines in the United States: Review of 2011.” Parsippany, NJ: IMS Health, April 2012. 9. IMS Health, Inc. “IMS National Prescription Audit™: December 2012.” Danbury, CT: IMS Health, 2012. 10. M.L. Aitken and E.R. Berndt. “Medicare Part D at Age Five: What Has Happened to Seniors' Prescription Drug Prices?” Parsippany, NJ: IMS Institute for Healthcare Informatics, July 2011. www.imshealth.com/ims/Global/Content/Home%20Page%20Content/IMS%20News/IHII_Medicare_Part_D2.pdf (accessed October 2012). 11. P.J. Cunningham. “Despite the Recession's Effects on Incomes and Jobs, the Share of People with High Medical Costs was Mostly Unchanged.” Health Affairs 2012; 31(11): 2563–2570. 3 • Spending and Costs 44
  • 49. Notes and Sources 12. PhRMA analysis based on Agency for Healthcare Research and Quality (AHRQ). “Medical Expenditure Panel Survey.” Rockville, MD: AHRQ, 2009. www.meps.ahrq.gov/mepsweb/ (accessed December 2012). Prescription drug spending includes brand and generic ingredients, pharmacy, and distribution costs. Estimates are not restricted to individuals with private coverage that includes prescription coverage, which can be expected to account for less than 2%. 13. Atlantic Information Services, Inc. (AIS). “Pharmacy Benefit Survey Results: 4th Quarter 2012.” 2012. www.AISHealth.com (accessed February 2013). 14. IMS Health, Inc. “IMS National Prescription Audit™: December 2012.” Danbury, CT: IMS Health, 2004–2012. 15. Express Scripts, Inc. “2009 Drug Trend Report.” St. Louis, MO: Express Scripts, April 2010. www.express- scripts.com/research/research/dtr/archive/2009/dtrfinal.pdf (accessed February 2013). 16. PhRMA analysis based on Organisation for Economic Co-operation and Development (OECD). “OECD Health Data 2012— Frequently Requested Data.” Paris, France: OECD Publishing, June 2012. www.oecd.org/els/healthpoliciesanddata/oecdhealthdata2012-frequentlyrequesteddata.htm (accessed December 2012). 3 • Spending and Costs 45
  • 50.
  • 51. 4 OUTCOMES AND SAVINGS Overcoming Gaps in Treatment, Improving Outcomes, and Reducing Costs through Better Use of Medicines Undertreatment of chronic disease and less than optimal use of prescribed medicines are significant public health problems, costing the U.S. economy hundreds of billions of dollars each year. Improved use of prescribed medicines, however, can result in better health outcomes, lower costs for other health care services, and increased worker productivity. 4 • Outcomes and Savings 47
  • 52. Most Americans Use Few or No Medicines — a Small Share of People Fill the Majority of Prescriptions The top 20% of people who used medicines accounted for almost two-thirds of all prescriptions filled in 2010. 100% 20% 64% 90% 80% 80% 70% (39% of the population 60% uses no medicines) 50% 40% 30% 36% 20% 10% 0% % of Population % of Prescription Fills Source: MEPS1 4 • Outcomes and Savings 48
  • 53. Medicines’ Changing Role in Recommended Care Revisions to clinical guidelines based on the latest research have resulted in appropriate increases in the use of medicines in recent years. Changes in the size of the treatable population as target levels change, such as lower targets for blood pressure, blood glucose, lipids Changes in the number and type of recommended medicines — such as a shift from single to combination therapy — to better control conditions Changes in therapeutic regimen and duration to better control conditions, such as longer continuation of treatment for depression Source: R.W. Dubois and B.B. Dean2 4 • Outcomes and Savings 49
  • 54. Failure to Prescribe the Indicated Treatment is the Most Common Prescribing Quality Problem RAND researchers report that failure to prescribe an indicated treatment is a far more common quality problem than is inappropriate medicine use. Quality Problems Among Vulnerable Older Patients Failure to prescribe when called 50% for by guidelines Inadequate monitoring 36% Inadequate education/ 19% continuity/ documentation Inappropriate medication 3% 0% 10% 20% 30% 40% 50% 60% Percentage of Quality Indicators Failed* *Quality indicators were developed and implemented based on systematic literature reviews and multiple layers of expert judgment. Source: RAND Health3 4 • Outcomes and Savings 50
  • 55. Diabetes: An Example of Underdiagnosis and Undertreatment Uncontrolled diabetes can lead to kidney failure, amputation, blindness, and stroke. 26 million Americans with DIABETES 19 million are DIAGNOSED 7 million are UNDIAGNOSED 16 million are TREATED 3 million are • Blood sugar control (diet and exercise, medicines) • diagnosed but • Testing to prevent complications • NOT TREATED 8 million receive some treatment 8 million are treated and have their but their disease is disease CONTROLLED NOT SUCCESSFULLY CONTROLLED 8 million have 18 million have UNCONTROLLED diabetes CONTROLLED diabetes Sources: CDC4; National Health and Nutrition Examination Survey (NHANES)5 4 • Outcomes and Savings 51
  • 56. Better Use of Medicines Improves Patient Health Diabetes patients who take their medicines as prescribed experience fewer complications. 18% 15.9% 15.7% 16% 14% 13.0% 11.8% 12% Likelihood of Event 10.8% 10.1% 10% 8.0% 7.8% 8% 5.8% 6% 4.0% 4.0% 4% 1.8% 2% 0% Acute Myocardial Amputation/ Ulcer Cerebrovascular Neuropathy Renal Events Retinopathy Infarction Disease Non-Adherent Patients Adherent Patients Source: T.B. Gibson, et al.6 4 • Outcomes and Savings 52
  • 57. Recommended Medicines Can Save Lives and Dramatically Improve Health “...achieving effective blood pressure control would be approximately equivalent to eliminating all deaths from accidents, or from influenza and pneumonia combined.” — David Cutler, Ph.D., Harvard University Annual Hospitalizations and Deaths Avoided through Use of Recommended Antihypertensive Medications Annual Hospitalizations Avoided Annual Premature Deaths Avoided Prevention Achieved: 833,000 86,000 Based on Current Treatment Rates Potential Additional Prevention: If Untreated Patients Received 420,000 89,000 Recommended Medicines Source: D.M. Cutler, et al.7 4 • Outcomes and Savings 53
  • 58. Prescription Medicines Are Part of the Solution to Controlling Medical Spending Better use of medicines reduces use of avoidable medical care, resulting in reductions in medical spending. Adherence to Medicines Lowers Total Health Spending for Chronically Ill Patients Drug Spending Medical Spending $2,000 $1,058 $656 $429 $601 Difference in Annual Spending Between Adherent and Nonadherent Patients $0 -$1,860 -$2,000 -$4,337 -$4,413 -$4,000 -$6,000 -$8,000 -$8,881 -$10,000 Congestive Heart Failure Diabetes Hypertension Dyslipidemia Source: M.C. Roebuck, et al.8 4 • Outcomes and Savings 54
  • 59. Gaining Drug Coverage Reduced Other Medical Spending The Medicare drug benefit increased access to medicines for those previously without drug coverage, resulting in reduced non-drug medical spending9 and overall savings of $13.4 billion in 2007, the first full year of the program.10 Average Reduction in Medical Spending in 2006 and 2007, for Beneficiaries Gaining Drug Coverage through Part D Average Total Spending Reduction per -$816 Beneficiary -$268 -$1,224 -$140 *Home health, durable medical equipment, hospice, and outpatient institutional services Sources: J.M. McWilliams, et al.9; C.C. Afendulis and M.E. Chernew10 4 • Outcomes and Savings 55
  • 60. Better Use of Medicines Yields Significant Health Gains and Savings on Other Services In 2012, the CBO announced that its budget estimates would recognize reductions in other medical expenditures associated with Medicare policy initiatives that increased the use of prescription medicines.11 Numerous studies demonstrate the value of better access to and use of medicines in improving health outcomes and reducing use of other medical services: • Better adherence to antihypertensive medications could save approximately 200,000 lives over 5 years.12 • Improved medication adherence among diabetes patients could prevent more than 1 million emergency department visits and hospitalizations annually, for potential savings of $8.3 billion each year.13 • Non-adherence has also been linked to excess hospitalizations for conditions such as chronic obstructive pulmonary disease,14,15 osteoporosis,16 congestive heart failure, hypertension, diabetes, and dyslipidemia,17 with costs of roughly $170 billion per year.18 Sources: CBO11; J.E. Bailey, et al.12; A.K. Jha, et al.13; B.C. Stuart, et al.14; L. Simoni-Wastila, et al.15 R. Halpern, et al.16; M.C. Roebuck, et al.17; and W.H. Schrank et al.18 4 • Outcomes and Savings 56
  • 61. High Cost-Sharing Reduces Adherence RAND researchers found that doubling co-pays reduced patients’ adherence to prescribed medicines by 25% to 45% and increased emergency-room visits and hospitalizations. Percent Change in Adherence from Doubling Medicine Co-pays 0% Percent Change in Days Supplied of Medicine -5% -10% -15% -20% -26% -26% -25% -25% -30% -33% -32% -34% -35% -40% -45% -44% -45% -50% Source: D.P. Goldman, et al.19 4 • Outcomes and Savings 57
  • 62. New Classes of Medicines Can Improve Adherence and Persistence Studies have found better adherence to newer medicines.20 Similar results have been found even when insurance requires higher patient cost-sharing for the newer medicines compared to older medicines.21 Persistence Patterns Among Antihypertensive Patients, by Drug Class 60% Prescribed Therapy After 48 Months Percentage of Patients Adhering to 50% 51% 47% 40% 41% 35% 30% 20% 16% 10% 0% Thiazide Diuretics (1957) Beta Blockers (1967) Calcium-Channel Blockers ACE Inhibitors (1981) ARBs (1995) (1981) Drug Class (Year of First Launch22) Sources: P.R. Conlin, et al.20; D.A. Taira, et al.21; FDA22 4 • Outcomes and Savings 58
  • 63. Notes and Sources 1. IHS Global Insight Analysis based on 2010 Medical Expenditure Panel Survey (MEPS). http://meps.ahrq.gov/mepsweb/ (accessed December 2012). 2. R.W. Dubois and B.B. Dean. “Evolution of Clinical Practice Guidelines: Evidence Supporting Expanded Use of Medicines.” Disease Management 2006; 9(4): 210–223. 3. RAND Health. "U.S. Healthcare Facts About Cost, Access, and Quality." Santa Monica, CA: RAND Corporation, 2005 citing T. Higashi, et al. "The Quality of Pharmacologic Care for Vulnerable Older Patients." Annals of Internal Medicine 2004; 140(9): 714– 720. 4. CDC. "National Diabetes Fact Sheet: National Estimates and General Information on Diabetes and Prediabetes in the United States, 2011." Atlanta, GA: HHS, CDC, 2011. www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf (accessed December 2012). 5. IHS Global Insight Analysis based on 2010 National Health and Nutrition Examination Survey (NHANES), Op. cit. 6. T.B. Gibson, et al. “Cost Sharing, Adherence, and Health Outcomes in Patients with Diabetes.” American Journal of Managed Care 2010; 16(8): 589–600. 7. D.M. Cutler, et al. “The Value of Antihypertensive Drugs: A Perspective on Medical Innovation.” Health Affairs 2007; 26(1): 97– 110. 8. M.C. Roebuck, et al. “Medication Adherence Leads to Lower Health Care Use and Costs Despite Increased Drug Spending.” Health Affairs 2011; 30(1): 91–99. 9. J.M. McWilliams, A.M. Zaslavsky, and H.A. Huskamp. “Implementation of Medicare Part D and Nondrug Medical Spending for Elderly Adults with Limited Prior Drug Coverage.” JAMA 2011; 306(4): 402–409. 10. C.C. Afendulis and M.E. Chernew. “State-Level Impacts of Medicare Part D.” American Journal of Managed Care 2011; 17 Suppl 12:S. 11. CBO. “Offsetting Effects of Prescription Drug Use on Medicare’s Spending for Medical Service.” Washington, DC: CBO, November 2012. 12. J.E. Bailey, et al. “Antihypertensive Medication Adherence, Ambulatory Visits, and Risk of Stroke and Death." Journal of General Internal Medicine 2010; 25(6): 495–503. 4 • Outcomes and Savings 59
  • 64. Notes and Sources 13. A.K. Jha, et al. “Greater Adherence to Diabetes Drugs is Linked to Less Hospital Use and Could Save Nearly $5 Billion Annually.” Health Affairs 2012; 31(8): 1836–1846. 14. B.C. Stuart, et al. “Impact of Maintenance Therapy on Hospitalization and Expenditures for Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease.” American Journal of Geriatric Pharmacotherapy 2010; 8(5): 441–453. 15. L. Simoni-Wastila, et al. “Association of Chronic Obstructive Pulmonary Disease Maintenance Medication Adherence With All- Cause Hospitalization and Spending in a Medicare Population.” American Journal of Geriatric Pharmacotherapy 2012; 10(3): 201–210. 16. R. Halpern, et al. “The Association of Adherence to Osteoporosis Therapies with Fracture, All-Cause Medical Costs, and All- Cause Hospitalizations: A Retrospective Claims Analysis of Female Health Plan Enrollees with Osteoporosis.” Journal of Managed Care Pharmacy 2011; 17(1): 25–39. 17. M.C. Roebuck, et al. “Medication Adherence Leads To Lower Health Care Use And Costs Despite Increased Drug Spending.” Health Affairs 2011; 30(1): 91–99. 18. W.H. Schrank, et al., "A Blueprint for Pharmacy Benefit Managers to Increase Value." American Journal of Managed Care 2009; 15(2): 87–93. 19. D.P. Goldman, et al. “Pharmacy Benefits and the Use of Drugs by the Chronically Ill.” JAMA 2004; 291(19): 2344–2350. 20. P.R. Conlin, et al. “Four-year Persistence Patterns Among Patients Initiating Therapy with the Angiotensin II Receptor Antagonist Losartan Versus Other Antihypertensive Drug Classes.” Clinical Therapeutics 2001; 23(12): 1999–2010. 21. D.A. Taira, et al. “Copayment Level and Compliance with Antihypertensive Medication: Analysis and Policy Implications for Managed Care.” American Journal of Managed Care 2006; 12(11): 678–683. 22. U.S. Food and Drug Administration. “Drugs@FDA: FDA Approved Drug Products.” www.accessdata.fda.gov/scripts/cder/drugsatfda/ (accessed July 2010). 4 • Outcomes and Savings 60
  • 65.
  • 66. 5 MARKETING AND PROMOTION Informing Consumers and Providers about Medicines Biopharmaceutical marketing and promotion are important and extensively regulated ways of informing consumers and health care professionals about medicines. Biopharmaceutical company representatives help speed the dissemination of improvements in medical care, and many physicians value this information. Direct-to-consumer advertising (DTCA) by biopharmaceutical companies can lead patients to seek additional information and consult their doctors about previously untreated conditions; it also informs patients about medicines’ risks and benefits. While marketing and promotion increase awareness of medical treatment options, other factors, including formulary design and utilization-management strategies, often have a greater impact on prescribing decisions. 5 • Marketing and Promotion 62
  • 67. Many Factors Affect Prescribing Decisions Factors Influencing Prescribing Decisions in the United States in 2011 Clinical knowledge and experience 84% 13% Patient's particular situation, including drug interactions, side effects, and contraindications 80% 16% Clinical practice guidelines 53% 39% Articles in peer-reviewed medical journals 47% 42% Information from colleagues and peers 40% 49% Patient's insurance coverage and formulary 40% 41% Information from pharmaceutical company representatives 18% 51% Pharmaceutical company-sponsored educational programs featuring physician speakers, not CME 17% 47% Information from insurance and prescription benefits manager representatives 15% 40% A great deal Some Source: KRC Research (survey of physicians)1 5 • Marketing and Promotion 63
  • 68. Physicians Find Biopharmaceutical Representatives’ Information Up-to-date, Useful, and Reliable Physicians’ Assessment of Biopharmaceutical Representatives’ Information Up-to-date and timely 38% 56% 94% Useful 32% 60% 92% Reliable 27% 57% 84% Strongly agree Somewhat agree Source: KRC Research (survey of physicians)2 5 • Marketing and Promotion 64
  • 69. Advertising Often Prompts Patients to Seek Additional Information Consumer Responses to Viewing Advertisements for Prescription Medicines 50% 45% 47% 40% 35% 30% 25% 27% 20% 15% 14% 10% 5% 8% 0% Sought Information Initiated Conversation Newly Aware of Requested Specific with Doctor Medical Condition Medication Source: Princeton Survey Research Associates International3 5 • Marketing and Promotion 65