1. Recruitment in Cancer Trials
Dr. Bhaswat S. Chakraborty
VP, R & D, Cadila

2. Patient Participation in Cancer Trials
 A 1999 press release from the American Society
of Clinical Oncologists
 only 3% of adults with cancer participate in clinical
trials
 far fewer than the number needed to answer the
most pressing cancer questions quickly
 Up to 80% of clinical trials are estimated to
experience problems with recruitment

3. A Survey on Clinical Trial Barriers
 A survey of almost 6,000 people with cancer conducted
in 2000
 85% were either unaware or unsure that participation in clinical
trials was an option
 75% said they would have been willing to enroll had they known
 of the aware ones of clinical trial option, most declined to
participate because of common myths about clinical trials:
 The medical treatment they would receive in a clinical trial would be less
effective than standard care
 They might get a placebo
 They would be treated like a "guinea pig"
 Their insurance company would not cover costs
Source: www.harrisinteractive.com/harris_poll/

4. A Survey on Clinical Trial Barriers
 People who received treatment through a clinical trial
found it to be a very positive experience:
 97% said they were treated with dignity and respect and
that the quality of care they received was "excellent" or
"good"
 Eighty-six percent said their treatment was covered by
insurance
Source: www.harrisinteractive.com/harris_poll/

5. Barriers & Promoters
 Barriers mainly 3 types
 barriers to opportunity to participate (most)
 barriers to awareness or acceptance of clinical trials
 cultural factors
 Promoters mainly 3 types
 awareness
 transport
 altruism

6. General Recruitment Issues
 Cancer trials require years to complete, and subject
recruitment and enrollment can be a lengthy process
 Planning and pilot testing of recruitment methods
 Monitoring of patient accrual with respect to a priori
targets
 Regular feedback of recruitment progress to recruiting
centres
 Development of a risk management plan to respond to
failure to achieve targets

7. Methodology to Particular Study
Recruitment Issues and Solutions
 Identify patient recruitment barriers through an extensive review
of the factors that hinder recruitment and retention
 eg. complicated protocols, over-rigorous inclusion and exclusion criteria,
etc.
 Identify solutions that work
 illustrated by extensive review and numerous case histories of strategies
and tactics that have been shown to improve recruitment and retention
 Obtain a thorough understanding of the circumstances in which
advertising can still offer a highly cost-effective means to recruit
patients and improve the quality and quantity of patients
enrolled.

8. Methodology to Study Recruitment
Issues and Solutions
 Get an in-depth look at the technological and other
innovations introduced by CROs and IT companies
 management of clinical trials generally and recruitment and
retention more specifically
 Understand why a growing number of clinical trials are
performed in countries like India
 cost benefits
 large populations
 pharmacogenetic profiling
 issues that sponsors to consider
 Gain reliable and thought-provoking insights into key
factors influencing patient recruitment

9. Main Barriers to Recruitment
 Patient age
 Comorbidity
 Disease stage
 Mistrust of research method and researchers
 Lack of physician/care giver awareness about trials
 Communication
 Method of IC presentation
 Community based approach versus Institution based
approach

10. Recruitment Strategies
 Hospitals, specialized hospitals
 The use of occupational and targeted screening
 Registers of trials
 Clinicians
 Mass media
 Direct mailing to access patients
 Specialized interventions
 Community camps

11. Barriers for Health Care
Professionals
 Lack of awareness of appropriate clinical trials
 physicians are not always aware of available clinical trials,
local resources
 some may assume that none would be appropriate for their
patients
 Unwillingness to "lose control" of a person's care
 relationship with patients is very important
 doctors fear they may lose control of the person's care
 Belief that standard therapy is best
 Belief that referring and/or participating in a clinical
trial adds an administrative burden
 Concerns about the person's care or how the person
will react to the suggestion of clinical trial participation

12. Specific Barriers
 Long-standing fear, apprehension, and skepticism
 Doctors may not mention clinical trials as an option for
cancer care.
 People from various cultural or ethnic backgrounds
hold different values and beliefs that may be different
than principles of Western medicine.
 Language or literacy barriers may make it difficult for
some people to understand and consider participating.
 Additional access problems confront many people

13. Cost Barriers
 The costs associated with clinical trials can be a barrier
for many professionals and the public
 Physicians are often concerned about reimbursement
related to the expense of either caring for people
enrolled in trials or offering trials within their practice
 Potential trial participants often fear that their insurance
company will not cover participation
 Those who are uninsured will need to know how their
participation in a trial will be covered.

14. Differences Between Passive and
Active Recruitment
 Patients were employees
 In the passive employee contact arm
 employees were contacted from a list of employee names and
telephone numbers provided by the company
 In the active employee contact arm
 employees actively signed up to participate
 While lower enrollment and higher attrition were observed in the
passive recruitment arm, the passive method enrolled a more diverse
group of participants than did the active recruitment method
Source: Linnan LA et al Ann Behav Med 2002;24(2):157-66

15. Effect of an Intervention Program
 Intervention program consisted of the installation of a rapid
tumor-reporting system
 to improve data quality and to expedite the receipt of information on
cancer patients from physicians
 a nurse facilitator who would notify physicians of clinical trials
 a quarterly newsletter mailed to physicians about cancer treatment and
clinical trials
 a health educator who trained lay health educators and provided
community-based information about cancer screening, treatment, and
clinical trials
 The rates of enrollment into clinical treatment trials did not
improve significantly in the intervention communities
Source:Ford Met al Clinical Trials 2004;1:343-51

16. Successful Recruitment
 Detailed understanding of the stages in the recruitment
process
 Identification of steps where potential patients are lost
 Development of alternative tactics to enhance
recruitment.
 Timeliness & cost containment
 Ability to detect subtle treatment effects
 Meeting ethical responsibilities to patients and clinicians
 Employment of an enthusiastic, committed and
talented staff
 Initiative and adaptability to recruitment problems

17. Successful Recruitment
 Invitation of keen and successful investigators
 Development of a comprehensive investigator's manual
 Organising investigator recruitment meetings
 Provision of numerous study aids to the centres
 Maintaining contact with the centres via the telephone
 Regular monitoring of recruitment progress and
strategies (with subsequent feedback to the centres via
the study newsletter and meetings for both the
investigators and study nurses).

18. Strategies for Successful Recruitment
(Hospitalized Patients)
 Provide checklists on patient charts with eligibility
criteria
 Placing posters with open protocols listed
 Using abridged "protocol pocket cards" with key
inclusion and exclusion criteria
 Dedicate one research nurse or research assistant
 to identifying and screening participants
 coordinating pre-enrollment tests
 educating participants about the protocol and process
 and initiating the informed consent and enrollment process
 Access funding for clinical trial support

19. Successful Recruitment
 One particular study
 the study nurse being employed for longer hours (P<0.001)
 the use of a coronary care register to identify eligible patients
(P=0.001)
 a systematic recruitment plan with targets and timetable
(P=0.02)
 the invitation of patients by both a personal letter and follow-
up phone call (P=0.09)
 regular contact with the patients' usual doctors and adequate
funding of centres
Source: NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia

20. Another Study: Recruitment
Facilitation Factors
 Interest in the research question, participation did not require any
unusual management practices
 Toll-free telephone randomisation and a simple one-page outcome
form each took only a few minutes to complete
 Well-organised and committed principal nurses
 Ongoing staff training
 Investigators’ meetings
 Regular communication and target setting
 Barrier
 minimal financial recompense for staff time
 many potentially eligible patients could not be recruited because of the lack of staff time to
dedicate to research
Source: Clinical Trials Research Unit, University of Auckland, Auckland, New Zealand

22. Three Critical Issues
 Risk to participants
 Practicality of Periodic Review of a Trial
 Scientific Validity of the Trial

23. Risk to Participants
 The study endpoint is such that a highly favorable or unfavorable result, or even
a finding of futility, at an interim analysis might ethically require termination of
the study before its planned completion
 There are a priori reasons for a particular safety concern, as, for example, if the
procedure for administering the treatment is particularly invasive
 There is prior information suggesting the possibility of serious toxicity with the
study treatment
 The study is being performed in a potentially fragile population such as
children, pregnant women or the very elderly, or other vulnerable populations,
such as those who are terminally ill or of diminished mental capacity
 The study is being performed in a population at elevated risk of death or other
serious outcomes, even when the study objective addresses a lesser endpoint
 The study is large, of long duration, and multi-center

24. Practicality of a DMC
 If the trial is likely to be completed quickly, the
DMC may not have an opportunity to have a
meaningful impact
 In short-term trials with important safety
concerns, however, a DMC may still be valuable

25. Scientific Validity of the Trial
 Recommendations to change
 inclusion criteria
 the trial endpoints
 or the size of the trial
 Scientific validity best evaluated by an unbiased
oversight committee
 with the exception of changes the Committee might
recommend on the basis of emerging safety concerns

26. A tt ention
f or Y our
Th a nks