Pharmaceutical development is a highly regulated business, and all types of operations must be clearly and thoroughly described in documents called Standard Operating Procedures (SOPs) guaranteeing quality and compliance. This requirement applies of course to the critical Interim Review and Analysis of clinical trials data by Data and Safety Monitoring Boards (DSMBs). Here are some instructions on writing the right SOPs for DSMB operations.
SOPs are in the heart of the quality system of pharmaceutical and biotechnology companies and are part of a quality pyramid rooted in the policies and standards that define the high-level approach of the company to various business topics and expands down to work instructions and even user manuals of different devices and software.
• Policies
o Standards
- SOPs
• Work Instructions
o User Manuals
Among these different levels, SOPs are the most important as they are auditable by health authorities and proof must me made that they have been followed exactly or that a deviation was decided and documented with reasonable rationale.
In order to plan, set up and operate DSMBs for clinical trials, a company must prepare and approve the necessary SOPs that comply not only with the company policies but also with national and international regulations and regulatory guidance from health authorities.
Here’s a detailed checklist of 9 elements that should be included in any DSMB SOP:
1. Revision History. Like all quality documents, the DSMB SOP must begin with a list of previous versions, dates of approval and effectiveness and a brief description of the changes. This is important because clinical trials are usually long and may cover more than one version of the SOP. In case of audit, any action taken will be reviewed against the SOP version in force at the time of the action.
2. Title. The title must be clear and comprehensive, for example when more than one acronym exists for the same type of committee. Title can be: Establishment and Operation of the Data Safety Monitoring Board (DSMB).
3. Purpose. Describe shortly the reason for this SOP.
4. Scope. Describe the type of studies (e.g., studies requiring a DSMB) and all sections of the company to which the SOP applies.
5. Roles and Responsibilities. List all internal personnel involved in the establishment and operation of the DSMB and describe their role and accountabilities. A table is the best way to present this information.
6. Procedure. This is the main part of the SOP and needs to clearly describe the actions, who must act, at which time and what the outcome is expected to be.
• Need for a DSMB. Describe first which studies will need to have a DSMB established and what are the criteria for such a choice. The nature, size and length of the study, the need for unblinded interim review and the option to terminate early either for safety of efficacy reasons are some of the typical reasons.
• DSMB members. Describe selection, recruitment and training:
– Who selects the members?
– What qualification must the members have (specialty, experience...)?
– What other conditions must the members meet (e.g., independence)
– Documentation to be provided for each member
– What steps must be taken
– What would be the role of a third party?
• DSMB Charter preparation. Describe here the following:
– Who should draft the DSMB charter?
– Use a template with at least the following elements
- Summary of the Study
- Purpose of the Study
- Composition of DSMB
- Roles and Responsibilities
- DSMB members
- Sponsor responsibilities
- Third Party and Independent Statistician responsibilities, if applicable
- Meeting Frequency
- Meeting Format and Voting
- Data to be Reviewed and Confidentiality of Interim Data Analysis (if applicable)
- DSMB Recommendation
- Sponsor Follow Up
– Review and approval procedures
• DSMB Charter updates.
– Who is responsible of updating the charter?
– Describe track changes and re-approval
• DSMB members change during the study. Describe the circumstances and sequence of events should the need arise for replacement of one of more members of the DSMB.
• Support to the DSMB from the sponsor. Describe who is responsible of providing data and other types of support to the DSMB from the sponsor’s side.
• DSMB Recommendations. The DSMB serves as an advisory body. The responsibility to accept, reject or clarify the recommendations rest solely with the sponsor.
– Describe the options for DSMB recommendation.
– Describe the sequence for receiving, reviewing and responding to the recommendations from the sponsor’s side including who is responsible.
• Implementation of DSMB recommendations. Describe the actions (if applicable) taken by the sponsor in response to the DSMB recommendations.
• Close-out of the DSMB. Upon completion of the DSMB responsibilities, or at the direction of the sponsor, the DSMB must be disbanded ensuring any contractual obligations are fulfilled and records are transferred to the Sponsor and all records are filed appropriately within the TMF.
7. Definitions, Acronyms and Abbreviations. List all that apply
8. References. Reference all available regulatory guidance and any related internal quality documents.
9. Approval Page. List the appropriate approvers and collect dates and signatures (paper or electronic).
DOWNLOAD NOW THE FREE DATA SAFETY MONITORING HANDBOOK
A single, integrated handbook regrouping various sources of information on when, why and how to set up and use DSMBs and DMCs.
