DATA SAFETY MONITORING BOARD IN CLINICAL TRIALS

DATA SAFETY MONITORING BOARD IN CLINICAL TRIALS

Data Safety Monitoring Board also called as Independent Data Monitoring Committee or Data Monitoring Committee or Data Review Board. A DSMB is a multidisciplinary committee established by the research sponsor to review the accumulation of trial data at regular intervals, in order to monitor the progress of a clinical trial. By making recommendations to the sponsor, or the Trial Steering Committee (TSC), on whether to proceed, modify or terminate a trial for safety or ethical reasons. Their task is to provide guidance on safety and/or trial conduct issues 

DSMBs play an important role in:

• safeguarding the interests of study participants

• ensuring that definitive and reliable findings are obtained which will accurately guide the future care of patients

• Improving the credibility of the trial.

Although investigators and sponsors monitor the day-to-day conduct of the trial, DSMBs make decisions on the overall conduct of the trial.

DSMBs are typically required for the following: 

1. Studies that pose greater than minimal risk 

2. Blinded studies 

3. Studies involving a vulnerable subjects (e.g., geriatric, pediatric cognitively impaired) 

4. Studies involving new therapies or science 

5. Studies involving dangerous procedures or highly toxic therapies

6. Studies with high expected rates of morbidity or mortality in the study population 

7. Studies with a high risk of early termination 

8. Multi-site studies—It is more difficult for an investigator to recognize a pattern of increased or unusual problems when he or she sees only a small fraction of study participants.

Characteristics of Data Safety Monitoring Boards

The main characteristic of a Data Safety Monitoring Board (DSMB) is should be free from any social, political, professional, business or financial influence.

Members of the DSMB are chosen and appointed by the sponsor, but they should be entirely independent of any ties to the trial, the sponsor, or any other action or individual that might influence their objectivity.

The scale and composition of the DSMB depends on the trial. Members with expertise in the field of ethics and the specific disease area as well as clinical and statistical skills shall be included. The terms and conditions of the appointment of individuals to the DSMB should be transparent, and the procedures of the DSMB should be well described and well documented.

DSMB Charter

A DSMB charter is a collection of written policies that define the functions, rules, and operations of the DSMB. Generally, a charter will include: 

• The objective of the DSMB

• Members responsibilities 

• The function and format of the DSMB meetings;

• Guidelines for Monitoring

• Processes for reporting (to and from the DSMB)

• The research data to be monitored, and how the data will be provided; and 

• The responsibilities of DSMB administrators. 

• The charter is intended to be a living document that members can at any moment, evaluate in order to decide if any changes to the protocol are appropriate.

External Data Safety Monitoring Boards 

For studies involving an external DSMB, such as industry-initiated and funded studies, the PI can follow the procedures outlined by the sponsor. In this case, a DSMB charter .is generally drawn by the sponsor. However, the PI must be prepared to provide the IRB with a record of composition of the DSMB, number of meetings and reports, and a plan to provide those reports.

Internal Data Safety Monitoring Boards 

1. Responsibilities 

a. Pre-enrollment meeting: The DSMB may meet prior to the enrollment of the first participant to discuss the study protocol, informed consent documentation, and DSMP. This analysis allows the DSMB to: 

 Determine the risks and benefits of the study, protections in place, and wellbeing of study           subjects

 Offer suggestions for improving the design of the study

 Reach agreement on the data that will be needed for review

 Determine the schedule of future meetings

 Appoint the chair person and voting member 

 Decide who will receives minutes and 

 Signing conflict of interest documents.

b. The issues referred to above must be resolved, irrespective of whether the DSMB formally convenes for a pre-enrollment meeting. 

2. This meeting may result in alteration of the safety plan provided for in the IRB application. If the DSMP is updated, the new plan should be sent to the IRB of the institution and to any relevant advisory committees.

a. Interim data review: The DSMB analyses interim data to detect evidence of efficacy or adverse effects and decide if the trial should proceed as initially designed, or whether it should be updated or halted.

b. Progress evaluation: The DSMB evaluates the progress of the trial, including periodic assessments of data quality/completeness, achievement of recruitment goals, compliance with the protocol, accumulation and retention of participants, and other factors that may affect the outcome of the study. 

c. Protection of confidentiality: The DSMB protects the confidentiality of study participants, data of the trial, and the results of the monitoring. 

3. Membership 

a. Appointment: The sponsor may independently appoint the DSMB; institution leadership may appoint DSMB members at their institution. 

b. Composition: The Board should include three or five members in total (always an odd number). If an efficacy assessment is part of the monitoring plan, a statistical monitoring plan is needed to ensure the validity of the study and the committee should include a biostatistician. Investigators are encouraged to consider the appointment of individuals from different units or divisions within and outside their institution. Membership of the Board must be determined and described prior to the submission of a scientific and human subjects review project.

c. Qualifications and responsibilities: Qualifications for membership are: 

(1) Expertise on the field, 

(2) Experience in the conduct of research and statistical knowledge on human subjects, 

(3) Liberty from the direct management of the research study, and

(4) Lack of conflict of interest or other conflicting commitments (i.e., should not be a co-investigator, not to be a direct report of any PI or co-investigator).

A chairperson will be appointed, and will be responsible for overseeing the meetings, developing the agenda, and summarising the conference. The chairperson shall be the contact person for the DSMB. 

Timing and Frequency of Meetings 

DSMB meetings will take place at least annually. The board may choose to meet periodically (e.g., quarterly or semiannually) if the risk to the subject is high, the population is vulnerable, there is a large amount of data to be reviewed, and/or after a pre-determined number of subjects have accrued. The chair may also call ad hoc meetings on the basis of safety or efficacy concerns. Meetings may be held by teleconference at the request of the board members.

Meeting Agenda 

1. The board will review required data (determined at the pre-enrollment meeting) provided by the investigator. 

2. As per the DSMP, The board will: 

a. Determine whether the study has adhered to the treatment plan 

b. Evaluate interim analysis, where appropriate and assess the relevant details to be analyzed 

c. Evaluate end point/stop point rules

d. Review protocol violations and deviations to determine the adequacy of the protocol

e. Ensure appropriate documentation of informed consent 

f. Review current enrollment information to:

i. Determine whether enrollment has followed eligibility criteria

ii. Ensure accrual is on target

iii. Assess visit compliance 

iv. Review screening failure information 

g. Review IND/IDE information 

h. Discuss investigator or key personnel changes

i. Review the quality of data collection forms and completeness

j. Assess the aggregate analysis of adverse events/serious adverse events

k. Review vital signs, clinical tests, etc

l. Review confidentiality 

Meeting Outcomes 

The major outcomes following data review include: 

1. Continuation of the trial, unmodified 

2. Modification of the protocol and/or consent form (for example, it could be unethical to begin providing placebo after a new therapy has been proven to be effective, or to continue new treatment if there is no possibility that the trials will be positive)

 3. Termination of the trial

CONCLUSION

DSMB plays a vital role in processing of ensuring the highest standards for research participants, data quality of clinical trials and medical safety. Clinical investigators, IRBs, drug regulators, industry, and sponsors are all influenced by the emerging role of DSMBs. The role of DSMBs increased due to an increase in the number of trials with mortality or severe morbidity as endpoints, there is a greater need to monitor the quality of the clinical trial data, and the demand for early termination of trials for safety or efficacy reasons.

-By

Jakkula Shirisha

Pharm.D

Student at Clinosol.