DATA AND SAFETY MONITORING BOARD (DSMB)

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

INTRODUCTION

• DSMB is a group of individuals with pertinent experience that reviews on aregular 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 andthose yet to be recruited to the trial, as well as the continuing validity andscientific merit of the trial.

OTHER NAMES:

• Data Monitoring Committee (DMC).

• Independent Data Monitoring Committee (IDMC).

• Data Review Board (DRB).

• The increasing use of DSMBs in industry-sponsored trials is the result ofseveral factors, including:

1) The growing number of industry-sponsored trials with mortality or majormorbidity endpoints

2) The increasing collaboration between industry and government insponsoring major clinical trials, resulting in industry trials performed underthe policies of government funding agencies, which often require DSMBs

3) Heightened awareness within the scientific community of problems inclinical trial conduct and analysis that might lead to inaccurate and/or biasedresults, especially when early termination for efficacy is a possibility, andneed for approaches to protect against such problems

4) Concerns of IRBs regarding ongoing trial monitoring and patient safety inmulticenter trials.

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 abilityto produce credible results

6) Ensure the credibility of the study

7) Ensure the validity of study results

DETERMINING NEED FOR A DSMB

• All clinical trials require safety monitoring, but not all trials requiremonitoring by a formal committee that may be external to the trialorganizers, sponsors, and investigators.

• DSMBs have generally been established for :

Large, randomized multisite studies that evaluate treatments intended toprolong life or reduce risk of a major adverse health outcome.

Any controlled trial of any size that will compare rates of mortality or majormorbidity .

• DSMBs are generally not needed for trials:

At early stages of product development

Addressing lesser outcomes, such as relief of symptoms, unless the trialpopulation is at elevated risk of more severe outcomes or involves a vulnerablepopulation.

• There are several factors to consider when determining whether toestablish 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?

WHAT IS THE RISK TO TRIAL PARTICIPANTS ?

• A fundamental reason to establish a DSMB is to enhance the safety of trialparticipants 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, oreven a finding of futility, at an interim analysis might ethically requiretermination of the study before its planned completion.

2) There are a priori reasons for a particular safety concern, as, for example, ifthe procedure for administering the treatment is particularly invasive.

3) There is prior information suggesting the possibility of serious toxicity withthe study treatment.

4) The study is being performed in a potentially fragile population such aschildren, pregnant women or the very elderly, or other vulnerablepopulations, such as those who are terminally ill or of diminished mentalcapacity.

5) The study is being performed in a population at elevated risk of death orother serious outcomes, even when the study objective addresses alesser endpoint.

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

IS DSMB REVIEW PRACTICAL?

• If the trial is likely to be completed quickly, the DSMB may not have anopportunity to have a meaningful impact.

• In short-term trials with important safety concerns, however, a DSMB maystill be valuable.

• In such cases, in order for the DSMB to be informed and convened quicklyin the event of unexpected results that raise concerns, the trial could buildin "pauses" so that interim data could be reviewed by a DSMB before anadditional cohort of participants would be enrolled.

WILL A DSMB HELP ASSURE THE SCIENTIFIC VALIDITY OF THE TRIAL?

• Trials of any appreciable duration can be affected by changes over time inthe understanding of the disease, the affected population, and the standardtreatment used outside the trial.

• These external changes may prompt an interest in modifying some aspectsof the trial as it progresses.

• DSMB suggests recommendations to modify the trial like changing theinclusion criteria, the trial endpoints, or the size of the trial. Suchrecommendations are best made by those without knowledge of theaccumulating data.

DSMB AND OTHER OVERSIGHT GROUPS

• These groups are components of a system that assists sponsors in conductingtrials 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

DSMB COMMITTEE COMPOSITION

• The sponsor and/or trial steering committee generally appoint members of aDSMB.

• Factors to consider in the selection of individuals to serve on a DSMB typicallyinclude:

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 forclinical 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.

• Some trials may require participation of:

1. Toxicologists, epidemiologists, and clinical pharmacologists in particularcases when such expertise appears important for informed interpretationof interim results.

2. One or more individuals (often non-scientists) who may help bring to theDSMB the perspectives of the population under study. Generally, such aDSMB member could be someone with the disease under study or a closerelative of such an individual.

3. Appropriate representation of gender and ethnic groups may be ofparticular importance for some trials.

4. DSMBs for international trials will usually include representatives from atleast a subset of participating countries or regions.

• 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 havereviewed

4. Conflicts of interest

Financial interest

Investigators entering subjects into the trial have a different type of conflict ofinterest—their knowledge of interim results could influence their conduct ofthe trial by changing the pattern of recruitment, or modify the usual way ofmonitoring 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 whenrepresentation of multiple scientific and other disciplines is desirable.

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

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 whenthe data are truly compelling and the risk of a false positive conclusion isacceptably low.

• A second type of consideration is whether the hypothesized benefit is likelyto 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 accrualrates are too low or noncompliance too great to provide adequate powerfor identifying the specified benefit, a DSMB may consider whethercontinuation of the study is futile and may recommend early termination onthis basis. However, in this case, false negative conclusions are of concern.

• In studies with serious outcomes, any major advances in the treatmentshould be identified and made available as soon as possible.

2. Monitoring for Safety:

• If subjects who are given the investigational intervention are found to beat higher risk for the outcome of interest (Ex: mortality, diseaseprogression, loss of organ function) sooner than those in the control, theDSMB may recommend early termination on safety grounds.

• However, such assessments have potential implications for falselyconcluding that there is an adverse effect.

• It is usually appropriate to demand less rigorous proof of harm to justifyearly termination than would be appropriate for a finding of benefit.

COMPARISON OF ADVERSE EVENT RATES IN EACH TREATMENT ARM:

• In some cases, adverse events of particular concern can be identified inadvance of the trial, and attention will be given to monitoring these events.

• Because many types of adverse reactions cannot be anticipated prior to alarge-scale study, the DSMB should be provided with interim summaries bytreatment arm of adverse events observed.

• This is particularly important for serious events that may result from thedisease being treated or with the intervention itself.

• An effect of the drug on these events can only be detected by comparing therates of the events in treatment and control groups.

CONSIDERATION OF INDIVIDUAL EVENTS OF PARTICULAR CONCERN:

• The responsibility of reviewing in detail every adverse event reported lies withthe sponsor, who must assure review of such events promptly.

• The involvement of a DSMB in the review of individual adverse event reportswill vary from case to case.

• The sponsor may ask the DSMB to review any individual event thought to be ofmajor significance by the study’s medical monitor; such events would generallyinclude deaths or other serious outcomes for which a causal connection withthe intervention is plausible.

• In some studies, it may be important for the DSMB to see detailedinformation on all deaths or other specified events that are likely to havebeen caused by the product being tested (e.g., acute liver failure in a drugstudy).

• In other studies, where many deaths or other serious events are expected,the DSMB may view only the summary tabulations and comparativestatistics to determine whether there appears to be an excess of animportant adverse event in one of the study arms.

• Concerns about the extent and type of adverse events observed may leadto early termination of the trial when the DSMB judges that the potentialbenefits of the intervention are unlikely to outweigh the risks.

• In other cases, a DSMB may recommend measures short of termination thatmight 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 beconcentrated in a particular subgroup.

2. Altering the product dosage and/or schedule if the adverse eventsobserved appear likely to be reduced by such changes.

3. Instituting screening procedures that could identify those at increased riskof a particular adverse event.

4. Informing current and future study participants of newly identified risks viachanges in the consent form and, in some cases, obtaining re-consent ofcurrent participants to continued study participation.

3. Monitoring Study Conduct :

• The DSMB shares responsibility for assessment of data related to studyconduct with the sponsor, the steering committee and to some extent withIRBs.

• A DSMB will review data related to the conduct of the study. These data mayinclude:

1. Rates of recruitment, ineligibility, noncompliance, protocol violations anddropouts, overall and by study site

2. Completeness and timeliness of data

3. Degree of concordance between site evaluation of events and centralizedreview

4. Balance between study arms on important prognostic variables

5. Accrual within important subsets.

The DSMB may issue recommendations to the sponsor regarding trialconduct when concerns arise that some aspects of trial conduct maythreaten the safety of participants or the integrity of the study.

4. Consideration of External Data :

• In some cases, particularly when unexpected safety issues arise in relatedstudies, the sponsor may bring external data to the attention of the DSMB.

• Then the DSMB may be asked to consider the impact of external informationon 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 fromthe sponsor to study participants describing the new results.

5. Studies of Less Serious Outcomes:

• These studies are generally short-term, evaluating treatment effect overperiods of a few days to a few months. DSMBs have not been commonlyestablished for such short-term studies.

• Early termination for effectiveness is rarely appropriate in such studies, exceptfor ethical reasons. In such a case, an outside group to monitor data regularlyis probably warranted. However, the sponsor will maintain the primary role ofmonitoring the accumulating results.

• Such a group may be particularly valuable when the patient population is atrelatively high risk of serious events; for example, in studies of drugs to controlsymptoms of angina, congestive heart failure, or chronic obstructive lungdisease.

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 maybe useful for certain types of early clinical studies.

• While these formal monitoring groups will often consist of individuals internalto the sponsor and/or investigators, a DSMB overseeing safety may beconsidered when risk to participants appears unusually high. Ex: With novelapproaches to treating a disease or condition.

• When the investigator is also the product manufacturer or IND sponsor, andthereby subject to potentially strong influences related to financial and/orintellectual incentives, a DSMB could provide additional, independentoversight that would enhance safety of study participants and the credibilityof the product development. Sponsors may therefore wish to considerestablishing DSMBs in such settings.

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 untilsome uncertainty is resolved.

• The rationale for recommendations should be clear and precise.

• Both a written recommendation and oral communication, withopportunity for questions and discussion, is advised.

2. Maintaining Meeting Records :

• The DSMB should keep minutes of all meetings.

• The DSMB should divide meeting minutes into two parts, according towhether they include discussion of confidential data (usually unblindedcomparative data).

• After each meeting, the DSMB should issue a written report to the sponsorbased on the meeting minutes.

• This report should include sufficient information to explain the rationale forany recommended changes.

• If no changes are recommended, the report may be as simple as "The DSMBrecommends that the study continue as designed."

DSMB RECOMMENDATIONS AND REGULATORY REPORTING REQUIREMENTS

• All clinical trials conducted under an IND are subject to regulatory safety reportingrequirements.

• In general, for an event that is individually recognizable as a serious eventpotentially related to administration of a medical product, the sponsor isresponsible for notifying the regulatory authority.

• The sponsor may make this notification with or without unblinding the individualcase, as appropriate.

• Findings conveyed to the sponsor by DSMB as part of a recommendation to modifythe trial could therefore mean that serious and unexpected events were occurring,and the sponsor would consequently be required to report an analysis of theseevents to the regulatory authority and to all study investigators.

• The sponsors should inform the regulatory authority about all recommendationsrelated to the safety of the investigational product whether or not the adverseevent in question meets the definition of "serious event."

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 aDSMB

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 shouldhave a data safety monitoring plan (DSMP) to assure the safety andwelfare of its participants.

DSMP

• A DSMP is a sponsor initiated process that describes how the principalinvestigator should plan to oversee the subject's safety and welfare.

• The intensity and frequency of monitoring should be tailored to fit theexpected 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

DSMB CHARTER

• Established by sponsor according to the data monitoring needs (includingscientific 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 withits responsibility, operational procedures, means of communications, anddecision-making procedures with regards to the sponsor, the investigator(s),study statistician, data manager, ethics committee(s),and regulatoryauthority(ies).

• 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, thecharter at the time of their appointment to the DSMB.

• Some of the items identified may be addressed within the charter; othersmay be addressed in separate standard operating procedures (SOPs).

• The decision as to which procedures should be included in the charter andwhich ones in separate SOPs will be specific to the study.

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

MEMBERSHIP

• Minimum of three members

• A procedure should be established concerning the requirements forcandidacy, including an outline of the duties and responsibilities of DSMBmembers.

• Procedures for membership should include the following:

1) The procedure for selecting members, including the method forappointing a member (e.g. by application, committee or personalinvitation).

2) The procedure for identifying conflicts of interest, and criteria fordetermining unacceptable conflicts of interest.

TERMS OF APPOINTMENT

• A procedure should be established identifying the terms of appointmentfor 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.

CONDITIONS OF APPOINTMENT

• A procedure stating the conditions of appointment should be drawn up; itshould include the requirements for:

1) A potential member to report in writing, at the time of candidacy, allpotential or real conflicts of interest to the sponsor.

2) A member to be willing to publicize his/her full name, profession, andaffiliation(s).

3) All reimbursement for work and expenses, if any, within or related to aDSMB to be recorded and made available to the public upon request.

4) A member to sign a confidentiality agreement regarding meetingdeliberations, applications, information on research participants,intervention and protocol-related information, study results and relatedmatters.

OFFICES

• For a well-functioning DSMB, procedures for the Board’s officers should beclearly 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).

INDEPENDENT CONSULTANTS

• The sponsor may call upon, or establish, a standing list of independentconsultants in accordance with the DSMB charter.

• Independent consultants provide special expertise to the DSMB; they may bespecialists in ethical or legal aspects, specific diseases or methodologies, orthey may be representatives of communities or special interest groups.

• For studies which have mortality or major morbidity as endpoints, a medicalmonitor may be requested to review reports of serious adverse events (SAEs)on an ongoing basis, in order to ensure good clinical care and identify earlysafety concerns.

• The medical monitor may be invited to report SAEs or other safety concernsat DSMB meetings.

EDUCATION FOR DSMB MEMBERS

• The conditions of appointment should state the provisions made fortraining of DSMB members in the work of a DSMB.

• The training should include an introduction to the study the participantswill be monitoring, and the charter for the DSMB on which they will beserving.

• When appropriate, staff should be provided to support the DSMB’s work.

• Measures to protect the confidentiality of the study and thepatients/subjects should be defined for the staff.

STAFF

QUORUM REQUIREMENTS

• The DSMB charter should establish specific quorum requirements forreviewing, and making recommendations on, the study, which shouldinclude:

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 themedical field of concern, and one biostatistician.

MEETING REQUIREMENTS

• The charter should specify the meetings to be held, including their expectedfrequency and venue.

• The charter should indicate whether the meetings will be held in person or byteleconference.

• Under exceptional circumstances, the DSMB may have to meet urgentlywithin a short time period. Procedures for this should be described in theDSMB charter.

• DSMB members should be given enough time to review the materials for themeeting.

• Minutes of the meeting should be documented, and finalized following anapproval procedure.

• Procedures for inviting the sponsor, investigator, independent consultants tothe meeting should be defined.

MEETING PROCEDURES

• Procedures for organization of the meetings should be developed inaccordance with the meeting requirements.

Organizational meeting

Early safety review meeting

Periodic review meetings

Final study closeout meeting

ORGANIZATIONAL MEETING

• This initial meeting should be attended by the DSMB members andrepresentatives 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 bythe 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.

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

PERIODIC REVIEW MEETINGS

• The expected frequency of these meetings should be specified.

• The agenda for each DSMB review meeting should be established basedon the discussions and recommendations from previous meetings andaccording to events in, or related to, the study that may have occurredsince the previous meeting.

• The meetings should review the efficacy and/or safety data generatedduring this period, and should include a progress report from theinvestigator.

• The DSMB should take into account the quality of conduct of the studyand the accuracy of the data.

FINAL STUDY CLOSEOUT MEETING

• At the termination or conclusion of a study, the DSMB may meet toconsider the efficacy and/or safety data generated from the study andprovide any final recommendation to the sponsor.

• A final assessment report can be considered.

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 whoassume responsibilities for the study while ensuring the independenceand integrity of the Board’s recommendation.

OPEN SESSION:

• The DSMB may request the attendance of the study team, steeringcommittee, investigator(s) and/or independent consultant(s) to providespecific clarification or respond to issues that have arisen.

• Open session discussion should focus on the conduct and progress of thestudy, and pay special attention to the pooled safety and efficacy data.

CLOSED SESSION:

• Only DSMB members should be present at the closed session.

• In this session, the DSMB should review the efficacy and safety data, attimes in unblinded format.

• The DSMB should consider the data in relation to the conduct andprogress of the study, and the study protocol.

• The DSMB should also decide, in closed session, on the writtenrecommendation it will present to the sponsor.

DSMB REVIEW OF THE SPONSOR’S REPORT

• The sponsor should report the safety and efficacy data, as well as otherrelevant study information, to the DSMB for its review.

• The sponsor’s report to the DSMB is often provided in two parts: an openpart and a closed part.

• The full report should be made available to DSMB members in advance (atleast one week) of the meeting.

• The charter should specify who will prepare and provide the open part ofthe report, and who will prepare and provide the closed part.

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.

CLOSED PART:

• The closed part of the sponsor’s report may include unblinded data andconfidential 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 aprevious confidential meeting.

• In blinded studies, the charter should outline when the DSMB will receivecompletely or partially unblinded data & who is responsible for unblindingthe data, the procedure for unblinding the data, and all parties who will haveaccess to unblinded data.

ARRIVING AT RECOMMENDATIONS

• In advising on the continuation, modification, suspension, or terminationof the study, the DSMB needs to take into account prior reviews, therequirements of applicable laws and regulations, and the scientific andethical appropriateness of continuing the study.

• Statistical analysis may provide evidence that justifies a recommendationbut consideration of all available data from the study or relevantinformation external to the study may be necessary to arrive at a morecomplete judgement.

• A DSMB should also take the following into consideration in its decision-making process:

1) Conflict of interest: Should be disclosed to the chairperson prior to themeeting and recorded in the minutes. A member should excusehimself/herself from the meeting during the decision procedure in case ofconflict of interest

2) The documents required for a full review of the study should be available toeach member, and the relevant elements mentioned in the safetymonitoring plan should be considered before a recommendation is made.

3) Only DSMB members who participate in the review should be involved inmaking a recommendation.

4) Recommendations should only be made at meetings where a quorum (asstipulated 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 besupported by clearly stated reasons.

MINUTES OF THE DSMB MEETING

• An appropriately detailed summary of the DSMB’s discussions should berecorded, with the recommendation clearly documented.

1) Minutes of open sessions should describe the proceedings of these sessionsat DSMB meetings, and summarize all DSMB findings, including therecommendation. These minutes should not contain any unblindedinformation because they may be distributed to the sponsor,investigator(s), and oversight groups.

2) Minutes of closed sessions should describe the proceedings of both theopen and closed sessions. This part should only be distributed to membersof the DSMB, unless otherwise specified in the charter.

COMMUNICATING THE DSMB RECOMMENDATION

• The recommendation should be communicated in writing to the sponsorwithin a predefined period, according to the DSMB charter and itsprocedures.

• 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 coordinatinginvestigator, when applicable.

4) The name of the study site(s).

5) The name (or some identifier) of the DSMB providing therecommendation.

6) The date and place when/where the recommendation was made.

7) A clear statement of the recommendation. In cases where therecommendation suggests modification, suspension, or termination of thestudy, clearly stated reason(s) for this need to be provided.

8) The signature (dated) of the chairperson (or other authorized person) ofthe DSMB.

9) Documentation of the delivery and receipt of the recommendation andits acknowledgement by the sponsor

DISTRIBUTION OF THE DSMB RECOMMENDATION

• The sponsor is responsible for distributing the recommendation, in atimely manner, to the steering committee, investigator(s), ethicscommittee(s), and regulatory authority(ies) involved in the study.

• Procedures for implementing the recommendation of the DSMB also needto be considered in advance.

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 tothe sponsor.

• 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 thathe/she understands his/her responsibilities and that he/she has no intereststhat conflict with the objective performance of his/her duties andresponsibilities as a member of the DSMB.

4) A record of all income and expenses of the DSMB, including payments andreimbursements 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’sreports.

8) A copy of the recommendation(s) provided by the DSMB to the sponsor.

9) A copy of all official DSMB correspondence.

THANK YOU