An important body that overlooks the conduct of CT including safety issues

1. DATA AND SAFETY MONITORING
BOARD (DSMB)

2. OVERVIEW
• Introduction
• Purpose of DSMB
• Need for a DSMB
• DSMB committee composition
• Responsibilities of the DSMB
• Data safety monitoring plan (DSMP)
• DSMB charter
• Operations of a DSMB
• Conclusion

3. INTRODUCTION
• DSMB is a group of individuals with pertinent experience that reviews on a
regular basis the accumulating data from an ongoing clinical trial.
• DSMB carries out important aspects of clinical trial monitoring.
• It is usually appointed by the sponsor.
• It advises the sponsor regarding the continuing safety of trial subjects and
those yet to be recruited to the trial, as well as the continuing validity and
scientific merit of the trial.
OTHER NAMES:
• Data Monitoring Committee (DMC).
• Independent Data Monitoring Committee (IDMC).
• Data Review Board (DRB).

4. • The increasing use of DSMBs in industry-sponsored trials is the result of
several factors, including:
1) The growing number of industry-sponsored trials with mortality or major
morbidity endpoints
2) The increasing collaboration between industry and government in
sponsoring major clinical trials, resulting in industry trials performed under
the policies of government funding agencies, which often require DSMBs
3) Heightened awareness within the scientific community of problems in
clinical trial conduct and analysis that might lead to inaccurate and/or biased
results, especially when early termination for efficacy is a possibility, and
need for approaches to protect against such problems
4) Concerns of IRBs regarding ongoing trial monitoring and patient safety in
multicenter trials.

5. PURPOSE OF A DSMB
1) Protect the safety of trial participants
2) Identify unacceptably slow rates of accrual
3) Identify high rates of ineligibility determined after randomization
4) Identify protocol violations and suggest changes to protocol
5) Identify unexpectedly high dropout rates that threaten the trial’s ability
to produce credible results
6) Ensure the credibility of the study
7) Ensure the validity of study results

6. DETERMINING NEED FOR A DSMB
• All clinical trials require safety monitoring, but not all trials require
monitoring by a formal committee that may be external to the trial
organizers, sponsors, and investigators.
• DSMBs have generally been established for :
 Large, randomized multisite studies that evaluate treatments intended to
prolong life or reduce risk of a major adverse health outcome.
 Any controlled trial of any size that will compare rates of mortality or major
morbidity .
• DSMBs are generally not needed for trials:
 At early stages of product development
 Addressing lesser outcomes, such as relief of symptoms, unless the trial
population is at elevated risk of more severe outcomes or involves a vulnerable
population.

7. • There are several factors to consider when determining whether to
establish a DSMB for a particular trial.
• These factors relate primarily to safety, practicality, and scientific validity.
– What is the risk to trial participants?
– Is DSMB review practical?
– Will a DSMB help assure the scientific validity of the trial?

8. WHAT IS THE RISK TO TRIAL PARTICIPANTS ?
• A fundamental reason to establish a DSMB is to enhance the safety of trial
participants in situations in which safety concerns may be unusually high.
• Sponsors should consider using a DSMB when:
1) The study endpoint is such that a highly favourable or unfavourable result, or
even a finding of futility, at an interim analysis might ethically require
termination of the study before its planned completion.
2) There are a priori reasons for a particular safety concern, as, for example, if
the procedure for administering the treatment is particularly invasive.
3) There is prior information suggesting the possibility of serious toxicity with
the study treatment.

9. 4) 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.
5) 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.
6) The study is large, of long duration, and multi-centre.

10. IS DSMB REVIEW PRACTICAL?
• If the trial is likely to be completed quickly, the DSMB may not have an
opportunity to have a meaningful impact.
• In short-term trials with important safety concerns, however, a DSMB may
still be valuable.
• In such cases, in order for the DSMB to be informed and convened quickly
in the event of unexpected results that raise concerns, the trial could build
in "pauses" so that interim data could be reviewed by a DSMB before an
additional cohort of participants would be enrolled.

11. WILL A DSMB HELP ASSURE THE SCIENTIFIC VALIDITY
OF THE TRIAL?
• Trials of any appreciable duration can be affected by changes over time in
the understanding of the disease, the affected population, and the standard
treatment used outside the trial.
• These external changes may prompt an interest in modifying some aspects
of the trial as it progresses.
• DSMB suggests recommendations to modify the trial like changing the
inclusion criteria, the trial endpoints, or the size of the trial. Such
recommendations are best made by those without knowledge of the
accumulating data.

12. DSMB AND OTHER OVERSIGHT GROUPS
• These groups are components of a system that assists sponsors in conducting
trials that are ethical and that produce valid and credible results.
1) Institutional Review Boards
2) Clinical Trial Steering Committees
3) Endpoint Assessment/Adjudication Committees
4) Site/Clinical Monitoring Committees
5) Others with Monitoring Responsibilities

13. DSMB COMMITTEE COMPOSITION
• The sponsor and/or trial steering committee generally appoint members of a
DSMB.
• Factors to consider in the selection of individuals to serve on a DSMB typically
include:
1) Relevant expertise
2) Experience in clinical trials and in serving on other DSMBs
3) Absence of serious conflicts of interest.
• Most DSMBs are composed of :
 Clinicians with expertise in relevant clinical specialties
 At least one biostatistician knowledgeable about statistical methods for
clinical trials and sequential analysis of trial data
 For trials with unusually high risks or with broad public health implications,
the DSMB may include a medical ethicist knowledgeable about the design,
conduct, and interpretation of clinical trials.

14. • Some trials may require participation of:
1. Toxicologists, epidemiologists, and clinical pharmacologists in particular
cases when such expertise appears important for informed interpretation
of interim results.
2. One or more individuals (often non-scientists) who may help bring to the
DSMB the perspectives of the population under study. Generally, such a
DSMB member could be someone with the disease under study or a close
relative of such an individual.
3. Appropriate representation of gender and ethnic groups may be of
particular importance for some trials.
4. DSMBs for international trials will usually include representatives from at
least a subset of participating countries or regions.

15. • The criteria for selecting all appointees should be:
1. Their respective expertise and experience
2. Their ability to commit to attending DSMB meetings
3. Their ability to maintain confidentiality of the interim results they have
reviewed
4. Conflicts of interest
 Financial interest
 Investigators entering subjects into the trial have a different type of conflict of
interest—their knowledge of interim results could influence their conduct of
the trial by changing the pattern of recruitment, or modify the usual way of
monitoring participants.
• In such cases, it’s recommended that DSMB members, for a given trial,
should not include investigators in that trial.
• A DSMB may have as few as 3 members, but may need to be larger when
representation of multiple scientific and other disciplines is desirable.

16. DSMB RESPONSIBILITIES
• Interim Monitoring:
– Monitoring for Effectiveness
– Monitoring for Safety
– Monitoring Study Conduct
– Consideration of External Data
– Studies of Less Serious Outcomes
• Early Studies
• Other Responsibilities
– Making Recommendations
– Maintaining Meeting Records

17. INTERIM MONITORING
1. Monitoring for Effectiveness:
• A DSMB, guided by a pre-specified statistical monitoring plan, will
recommend early termination on the basis of a positive result only when
the data are truly compelling and the risk of a false positive conclusion is
acceptably low.
• A second type of consideration is whether the hypothesized benefit is likely
to be achieved.
• If the interim data suggest that the new product is of no benefit—that is,
there is no trend indicating superiority of the new product—or that accrual
rates are too low or noncompliance too great to provide adequate power
for identifying the specified benefit, a DSMB may consider whether
continuation of the study is futile and may recommend early termination on
this basis. However, in this case, false negative conclusions are of concern.
• In studies with serious outcomes, any major advances in the treatment
should be identified and made available as soon as possible.

18. 2. Monitoring for Safety:
• If subjects who are given the investigational intervention are found to be
at higher risk for the outcome of interest (Ex: mortality, disease
progression, loss of organ function) sooner than those in the control, the
DSMB may recommend early termination on safety grounds.
• However, such assessments have potential implications for falsely
concluding that there is an adverse effect.
• It is usually appropriate to demand less rigorous proof of harm to justify
early termination than would be appropriate for a finding of benefit.

19. COMPARISON OF ADVERSE EVENT RATES IN EACH TREATMENT ARM:
• In some cases, adverse events of particular concern can be identified in
advance of the trial, and attention will be given to monitoring these events.
• Because many types of adverse reactions cannot be anticipated prior to a
large-scale study, the DSMB should be provided with interim summaries by
treatment arm of adverse events observed.
• This is particularly important for serious events that may result from the
disease being treated or with the intervention itself.
• An effect of the drug on these events can only be detected by comparing the
rates of the events in treatment and control groups.

20. CONSIDERATION OF INDIVIDUAL EVENTS OF PARTICULAR CONCERN:
• The responsibility of reviewing in detail every adverse event reported lies with
the sponsor, who must assure review of such events promptly.
• The involvement of a DSMB in the review of individual adverse event reports
will vary from case to case.
• The sponsor may ask the DSMB to review any individual event thought to be of
major significance by the study’s medical monitor; such events would generally
include deaths or other serious outcomes for which a causal connection with
the intervention is plausible.

21. • In some studies, it may be important for the DSMB to see detailed
information on all deaths or other specified events that are likely to have
been caused by the product being tested (e.g., acute liver failure in a drug
study).
• In other studies, where many deaths or other serious events are expected,
the DSMB may view only the summary tabulations and comparative
statistics to determine whether there appears to be an excess of an
important adverse event in one of the study arms.
• Concerns about the extent and type of adverse events observed may lead
to early termination of the trial when the DSMB judges that the potential
benefits of the intervention are unlikely to outweigh the risks.

22. • In other cases, a DSMB may recommend measures short of termination that
might reduce the risk of adverse events.
• For example, the DSMB might recommend:
1. Changing the eligibility criteria if the risks of the intervention seem to be
concentrated in a particular subgroup.
2. Altering the product dosage and/or schedule if the adverse events
observed appear likely to be reduced by such changes.
3. Instituting screening procedures that could identify those at increased risk
of a particular adverse event.
4. Informing current and future study participants of newly identified risks via
changes in the consent form and, in some cases, obtaining re-consent of
current participants to continued study participation.

23. 3. Monitoring Study Conduct :
• The DSMB shares responsibility for assessment of data related to study
conduct with the sponsor, the steering committee and to some extent with
IRBs.
• A DSMB will review data related to the conduct of the study. These data may
include:
1. Rates of recruitment, ineligibility, noncompliance, protocol violations and
dropouts, overall and by study site
2. Completeness and timeliness of data
3. Degree of concordance between site evaluation of events and centralized
review
4. Balance between study arms on important prognostic variables
5. Accrual within important subsets.
The DSMB may issue recommendations to the sponsor regarding trial
conduct when concerns arise that some aspects of trial conduct may
threaten the safety of participants or the integrity of the study.

24. 4. Consideration of External Data :
• In some cases, particularly when unexpected safety issues arise in related
studies, the sponsor may bring external data to the attention of the DSMB.
• Then the DSMB may be asked to consider the impact of external information
on the study being monitored.
• Such data may lead to recommendations like:
 Termination of the study or one or more study arms
 Changes in target population, dose and/or duration of the intervention
 Use of concomitant treatments
 Changes to the consent form or investigator’s brochure, and/or letters from
the sponsor to study participants describing the new results.

25. 5. Studies of Less Serious Outcomes:
• These studies are generally short-term, evaluating treatment effect over
periods of a few days to a few months. DSMBs have not been commonly
established for such short-term studies.
• Early termination for effectiveness is rarely appropriate in such studies, except
for ethical reasons. In such a case, an outside group to monitor data regularly
is probably warranted. However, the sponsor will maintain the primary role of
monitoring the accumulating results.
• Such a group may be particularly valuable when the patient population is at
relatively high risk of serious events; for example, in studies of drugs to control
symptoms of angina, congestive heart failure, or chronic obstructive lung
disease.

26. EARLY STUDIES
• DSMBs are not usually warranted in early studies such as Phase 1 or early
Phase 2 studies, or pilot/feasibility studies, but formal monitoring groups may
be useful for certain types of early clinical studies.
• While these formal monitoring groups will often consist of individuals internal
to the sponsor and/or investigators, a DSMB overseeing safety may be
considered when risk to participants appears unusually high. Ex: With novel
approaches to treating a disease or condition.
• When the investigator is also the product manufacturer or IND sponsor, and
thereby subject to potentially strong influences related to financial and/or
intellectual incentives, a DSMB could provide additional, independent
oversight that would enhance safety of study participants and the credibility
of the product development. Sponsors may therefore wish to consider
establishing DSMBs in such settings.

27. OTHER RESPONSIBILITIES
1. Making Recommendations:
• A fundamental responsibility of a DSMB is to make recommendations to
the sponsor concerning the continuation of the study.
• The DSMB’s recommendations after an interim review may be:
• Study to continue as designed
• Study termination
• Study continuation with major or minor modifications
• Temporary suspension of enrollment and/or study intervention until
some uncertainty is resolved.
• The rationale for recommendations should be clear and precise.
• Both a written recommendation and oral communication, with
opportunity for questions and discussion, is advised.

28. 2. Maintaining Meeting Records :
• The DSMB should keep minutes of all meetings.
• The DSMB should divide meeting minutes into two parts, according to
whether they include discussion of confidential data (usually unblinded
comparative data).
• After each meeting, the DSMB should issue a written report to the sponsor
based on the meeting minutes.
• This report should include sufficient information to explain the rationale for
any recommended changes.
• If no changes are recommended, the report may be as simple as "The DSMB
recommends that the study continue as designed."

29. DSMB RECOMMENDATIONS AND REGULATORY REPORTING
REQUIREMENTS
• All clinical trials conducted under an IND are subject to regulatory safety reporting
requirements.
• In general, for an event that is individually recognizable as a serious event
potentially related to administration of a medical product, the sponsor is
responsible for notifying the regulatory authority.
• The sponsor may make this notification with or without unblinding the individual
case, as appropriate.
• Findings conveyed to the sponsor by DSMB as part of a recommendation to modify
the trial could therefore mean that serious and unexpected events were occurring,
and the sponsor would consequently be required to report an analysis of these
events to the regulatory authority and to all study investigators.
• The sponsors should inform the regulatory authority about all recommendations
related to the safety of the investigational product whether or not the adverse
event in question meets the definition of "serious event."

30. DO ALL STUDIES NEED AN INDEPENDENT DSMB?
• Studies that do not need an independent DSMB include:
1) Studies that have too few subjects to support statistical analysis by a
DSMB
2) Early phase non-randomized trials with limited safety concerns
3) Studies with rapid recruitment
4) Studies with short-term endpoints
• However, all studies posing more than minimal risk to the subjects should
have a data safety monitoring plan (DSMP) to assure the safety and
welfare of its participants.

31. DSMP
• A DSMP is a sponsor initiated process that describes how the principal
investigator should plan to oversee the subject's safety and welfare.
• The intensity and frequency of monitoring should be tailored to fit the
expected risk level, complexity, and size of the particular study.
ESSENTIAL ELEMENTS OF THE DSMP
• The plan should describe processes for dealing with the following:
1. Monitoring the Progress and Safety of the Trial
2. Reporting of Unanticipated Problems
3. Reporting of Suspensions or Terminations
4. Assuring Data Accuracy and Protocol Compliance

32. DSMB CHARTER
• Established by sponsor according to the data monitoring needs (including
scientific and ethical) of the particular study.
• Defines the relationship between the sponsor and the DSMB.
• Indicates the authority under which the DSMB is constituted together with
its responsibility, operational procedures, means of communications, and
decision-making procedures with regards to the sponsor, the investigator(s),
study statistician, data manager, ethics committee(s),and regulatory
authority(ies).

33. • The following items should be addressed in the charter.
1) Description
2) Objectives
3) Meeting arrangements
4) Data management and security
5) Documentation
• After reviewing the charter, all DSMB members should agree to, and sign, the
charter at the time of their appointment to the DSMB.
• Some of the items identified may be addressed within the charter; others
may be addressed in separate standard operating procedures (SOPs).
• The decision as to which procedures should be included in the charter and
which ones in separate SOPs will be specific to the study.

34. OPERATIONS (SOPs) OF A DSMB
Developed by the sponsor in accordance with the needs of the charter.
1) Membership
2) Terms of appointment
3) Conditions of appointment
4) Offices
5) Independent consultants
6) Conflict of interest
7) Education for DSMB members
8) Staff
9) Quorum requirements
10) Meeting procedures
11) Format of meetings
12) DSMB review of the sponsor’s
report
13) Arriving at recommendations
14) Minutes of the DSMB meeting
15) Communicating the DSMB
recommendation
16) Distribution of the DSMB
recommendation
17) Documentation and archiving

35. MEMBERSHIP
• Minimum of three members
• A procedure should be established concerning the requirements for
candidacy, including an outline of the duties and responsibilities of DSMB
members.
• Procedures for membership should include the following:
1) The procedure for selecting members, including the method for
appointing a member (e.g. by application, committee or personal
invitation).
2) The procedure for identifying conflicts of interest, and criteria for
determining unacceptable conflicts of interest.

36. TERMS OF APPOINTMENT
• A procedure should be established identifying the terms of appointment
for members of the DSMB, including:
1) The duration of appointment.
2) The policy for renewal of an appointment.
3) The disqualification procedure.
4) The resignation procedure.
5) The replacement procedure.

37. CONDITIONS OF APPOINTMENT
• A procedure stating the conditions of appointment should be drawn up; it
should include the requirements for:
1) A potential member to report in writing, at the time of candidacy, all
potential or real conflicts of interest to the sponsor.
2) A member to be willing to publicize his/her full name, profession, and
affiliation(s).
3) All reimbursement for work and expenses, if any, within or related to a
DSMB to be recorded and made available to the public upon request.
4) A member to sign a confidentiality agreement regarding meeting
deliberations, applications, information on research participants,
intervention and protocol-related information, study results and related
matters.

38. OFFICES
• For a well-functioning DSMB, procedures for the Board’s officers should be
clearly defined.
• A description is required of:
1) The officers within the DSMB (Ex: Chairperson, secretary)
2) The requirements for holding each office
3) The terms and conditions of each office
4) The duties and responsibilities of each office (Ex: Agenda, minutes,
notification of recommendations).

39. INDEPENDENT CONSULTANTS
• The sponsor may call upon, or establish, a standing list of independent
consultants in accordance with the DSMB charter.
• Independent consultants provide special expertise to the DSMB; they may be
specialists in ethical or legal aspects, specific diseases or methodologies, or
they may be representatives of communities or special interest groups.
• For studies which have mortality or major morbidity as endpoints, a medical
monitor may be requested to review reports of serious adverse events (SAEs)
on an ongoing basis, in order to ensure good clinical care and identify early
safety concerns.
• The medical monitor may be invited to report SAEs or other safety concerns
at DSMB meetings.

40. EDUCATION FOR DSMB MEMBERS
• The conditions of appointment should state the provisions made for
training of DSMB members in the work of a DSMB.
• The training should include an introduction to the study the participants
will be monitoring, and the charter for the DSMB on which they will be
serving.
• When appropriate, staff should be provided to support the DSMB’s work.
• Measures to protect the confidentiality of the study and the
patients/subjects should be defined for the staff.
STAFF

41. QUORUM REQUIREMENTS
• The DSMB charter should establish specific quorum requirements for
reviewing, and making recommendations on, the study, which should
include:
1) The minimum number of members required to compose a quorum (Ex:
More than half the members).
2) The professional qualifications required (e.g. physician, biostatistician,
paramedic, ethics).
• A quorum should include at least one physician with experience in the
medical field of concern, and one biostatistician.

42. MEETING REQUIREMENTS
• The charter should specify the meetings to be held, including their expected
frequency and venue.
• The charter should indicate whether the meetings will be held in person or by
teleconference.
• Under exceptional circumstances, the DSMB may have to meet urgently
within a short time period. Procedures for this should be described in the
DSMB charter.
• DSMB members should be given enough time to review the materials for the
meeting.
• Minutes of the meeting should be documented, and finalized following an
approval procedure.
• Procedures for inviting the sponsor, investigator, independent consultants to
the meeting should be defined.

43. MEETING PROCEDURES
• Procedures for organization of the meetings should be developed in
accordance with the meeting requirements.
 Organizational meeting
 Early safety review meeting
 Periodic review meetings
 Final study closeout meeting

44. ORGANIZATIONAL MEETING
• This initial meeting should be attended by the DSMB members and
representatives of the sponsor; members of the study staff and the investigator(s)
may also be invited.
• This meeting takes place prior to finalization of the study protocol and review by
the ethics committee(s).
• The DSMB members should review and discuss:
 Role and responsibilities of the DSMB
 Protocol
 Informed consent documents, prior ethics committee(s) reviews
 Investigator’s brochure
 Safety monitoring plan
 Statistical methodology
 Relevant literature and other research-related document(s).
 Requirements of applicable laws and regulations.
• The DSMB may, in the context of this discussion, propose changes to the charter.

45. EARLY SAFETY REVIEW MEETING
• Held during the early stages of implementation of a study
• To review:
 Early safety information and
 Factors relating to quality of conduct of the study

46. PERIODIC REVIEW MEETINGS
• The expected frequency of these meetings should be specified.
• The agenda for each DSMB review meeting should be established based
on the discussions and recommendations from previous meetings and
according to events in, or related to, the study that may have occurred
since the previous meeting.
• The meetings should review the efficacy and/or safety data generated
during this period, and should include a progress report from the
investigator.
• The DSMB should take into account the quality of conduct of the study
and the accuracy of the data.

47. FINAL STUDY CLOSEOUT MEETING
• At the termination or conclusion of a study, the DSMB may meet to
consider the efficacy and/or safety data generated from the study and
provide any final recommendation to the sponsor.
• A final assessment report can be considered.

48. FORMAT OF MEETINGS
• It is recommended that each DSMB meeting be divided into two sessions:
an open session and a closed session.
• This will enable the DSMB to interact with groups and individuals who
assume responsibilities for the study while ensuring the independence
and integrity of the Board’s recommendation.
OPEN SESSION:
• The DSMB may request the attendance of the study team, steering
committee, investigator(s) and/or independent consultant(s) to provide
specific clarification or respond to issues that have arisen.
• Open session discussion should focus on the conduct and progress of the
study, and pay special attention to the pooled safety and efficacy data.

49. CLOSED SESSION:
• Only DSMB members should be present at the closed session.
• In this session, the DSMB should review the efficacy and safety data, at
times in unblinded format.
• The DSMB should consider the data in relation to the conduct and
progress of the study, and the study protocol.
• The DSMB should also decide, in closed session, on the written
recommendation it will present to the sponsor.

50. DSMB REVIEW OF THE SPONSOR’S REPORT
• The sponsor should report the safety and efficacy data, as well as other
relevant study information, to the DSMB for its review.
• The sponsor’s report to the DSMB is often provided in two parts: an open
part and a closed part.
• The full report should be made available to DSMB members in advance (at
least one week) of the meeting.
• The charter should specify who will prepare and provide the open part of
the report, and who will prepare and provide the closed part.

51. OPEN PART:
• The open part of the sponsor’s report should include blinded and non-
confidential data:
 Participant recruitment
 Baseline characteristics, and pooled data on eligibility violations
 Completeness of follow-up
 Protocol compliance
 Problems encountered in the conduct of the protocol, and
 Any new information/publications that bear on the study.

52. CLOSED PART:
• The closed part of the sponsor’s report may include unblinded data and
confidential information:
 Unblinded analyses of primary and secondary endpoints
 Analysis of SAEs for severity and seriousness
 Analyses of laboratory data
 Summary of global and site-specific safety data, and
 Any other information from the sponsor or study sites during this or a
previous confidential meeting.
• In blinded studies, the charter should outline when the DSMB will receive
completely or partially unblinded data & who is responsible for unblinding
the data, the procedure for unblinding the data, and all parties who will have
access to unblinded data.

53. ARRIVING AT RECOMMENDATIONS
• In advising on the continuation, modification, suspension, or termination
of the study, the DSMB needs to take into account prior reviews, the
requirements of applicable laws and regulations, and the scientific and
ethical appropriateness of continuing the study.
• Statistical analysis may provide evidence that justifies a recommendation
but consideration of all available data from the study or relevant
information external to the study may be necessary to arrive at a more
complete judgement.
• A DSMB should also take the following into consideration in its decision-
making process:

54. 1) Conflict of interest: Should be disclosed to the chairperson prior to the
meeting and recorded in the minutes. A member should excuse
himself/herself from the meeting during the decision procedure in case of
conflict of interest
2) The documents required for a full review of the study should be available to
each member, and the relevant elements mentioned in the safety
monitoring plan should be considered before a recommendation is made.
3) Only DSMB members who participate in the review should be involved in
making a recommendation.
4) Recommendations should only be made at meetings where a quorum (as
stipulated in the charter) is present.
5) There should be a predefined method for arriving at a recommendation
(e.g. by consensus, by vote).
6) A recommendation to modify, suspend, or terminate the study should be
supported by clearly stated reasons.

55. MINUTES OF THE DSMB MEETING
• An appropriately detailed summary of the DSMB’s discussions should be
recorded, with the recommendation clearly documented.
1) Minutes of open sessions should describe the proceedings of these sessions
at DSMB meetings, and summarize all DSMB findings, including the
recommendation. These minutes should not contain any unblinded
information because they may be distributed to the sponsor,
investigator(s), and oversight groups.
2) Minutes of closed sessions should describe the proceedings of both the
open and closed sessions. This part should only be distributed to members
of the DSMB, unless otherwise specified in the charter.

56. COMMUNICATING THE DSMB
RECOMMENDATION
• The recommendation should be communicated in writing to the sponsor
within a predefined period, according to the DSMB charter and its
procedures.
• This communication should include, but is not limited to, the following:
1) The exact title of the study reviewed.
2) Clearly identified date and version/number of the study.
3) The name and title of the principal investigator(s) or the coordinating
investigator, when applicable.
4) The name of the study site(s).
5) The name (or some identifier) of the DSMB providing the
recommendation.

57. 6) The date and place when/where the recommendation was made.
7) A clear statement of the recommendation. In cases where the
recommendation suggests modification, suspension, or termination of the
study, clearly stated reason(s) for this need to be provided.
8) The signature (dated) of the chairperson (or other authorized person) of
the DSMB.
9) Documentation of the delivery and receipt of the recommendation and
its acknowledgement by the sponsor

58. DISTRIBUTION OF THE DSMB
RECOMMENDATION
• The sponsor is responsible for distributing the recommendation, in a
timely manner, to the steering committee, investigator(s), ethics
committee(s), and regulatory authority(ies) involved in the study.
• Procedures for implementing the recommendation of the DSMB also need
to be considered in advance.

59. DOCUMENTATION AND ARCHIVING
• All documentation and communications of a DSMB should be dated, filed,
and archived according to written procedures.
• The documents should be archived for the duration of study.
• At the closure of the study, the archived materials should be forwarded to
the sponsor.

60. • Documents that should be filed and archived include, but are not limited to:
1) The DSMB charter.
2) The curricula vitae of all DSMB members.
3) A signed and dated statement from each DSMB member indicating that
he/she understands his/her responsibilities and that he/she has no interests
that conflict with the objective performance of his/her duties and
responsibilities as a member of the DSMB.
4) A record of all income and expenses of the DSMB, including payments and
reimbursements made to the DSMB members.
5) The agendas of DSMB meetings.
6) The minutes of DSMB meetings.
7) A copy of all materials received by the DSMB, including the sponsor’s
reports.
8) A copy of the recommendation(s) provided by the DSMB to the sponsor.
9) A copy of all official DSMB correspondence.

61. THANK YOU