GCP Compliance for DSMBs and DMCs: How to ensure?

Clinical trials must comply with the Good Clinical Practices (GCP) that protect human subjects participating in the studies. A Data Safety Monitoring Board (DSMB) or Data Monitoring Committee (DMC) reviews unblinded summary data and provides guidance on the conduct of the trial. Its members are independent experts with no other vested interest and provide unbiased advice. Is this sufficient or should the DSMB also abide by the GCP rules? And if so, how can a software platform support compliance?

Good clinical practice (GCP) is an international ethical and scientific quality standard for designing, recording and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety and wellbeing of trial subjects are protected and that clinical-trial data are credible¹. 

ICH E6 Good Clinical Practice (GCP) Guideline

Today, the E6 Good Clinical Practice (GCP) guideline developed by the International Conference of Harmonization (ICH) is used in clinical trials throughout the globe. According to this guidance, the following must be ensured in a GCP compliant study:

• Quality, integrity, and reliability of research data
• Confidentiality of personal records
• Accurate reporting, interpretation, and verification of the data
• Use of systems with written procedures (SOP)
• Maintenance of written records, and if these are electronic
• Compliance with 21CFRpart11 rules

DSMBs and patient protection

Blinding of patients, investigators and sponsors to the treatment received by each subject in a clinical trial is essential for the unbiased collection of data and the sound analysis of results but comes with the risk that a study may continue, sometimes for long periods, unnecessarily either because the investigational drug does not work, has unacceptable side effects or, on the contrary, works unexpectedly well and the development should move on faster than initially planned. 

A Data Safety Monitoring Board (DSMB) also called Data Monitoring Committee (DMC) is authorized to review unblinded aggregate data from a clinical trial at regular intervals and provide guidance on the conduct without compromising the blinding. DSMB members are experts in the field under investigation but have no other vested interest in the study, the drug, or the sponsor so they can advise in an efficient and unbiased way on the path to follow. Should the setup of a DSMB, in addition to these restrictions, also follow the GCP rules? The answer is definitely yes and here are some of the reasons why:

• GCP require quality, integrity, and reliability of the data. It is essential to ensure that all data presented to the DSMB for review and decision respect these principles.
• GCP protect the confidentiality of certain records in particular personal identifying information for the subjects of the trial. DSMB proceedings must apply anonymization rules and procedures to ensure adequate protection of this information.
• GCP require accurate reporting, interpretation, and verification of all data. DSMB proceedings must also abide by these rules. Therefore, all data presented to the DSMB to support decisions and all resulting information must also be accurately reported and interpreted and must be verifiable at all times.
• In line with GCP, the DSMB must operate with written procedures (SOP) and following a specific written charter to ensure quality of the proceedings.
• GCP require transparent, verifiable recording of all data and decisions. Therefore, all discussions and decisions made during DSMB meetings must be recorded and stored in the TMF for future inspection. An audit trail, either manual or electronic, of all data, decisions and operations guarantees that no accidental or intentional changes are made at any later time.
• When using electronic documents and electronic signatures, specific rules such as 21CFRpart 11 must be followed. 

eDSMB® software and GCP compliance

Compliance with Good Clinical Practice (GCP) in order to protect patients impose a high administrative burden to clinical teams when preparing and running clinical trials and the DSMB process adds additional workload. Adopting a validated electronic tool such as eDSMB® ensures:  

• Secure and confidential data management, 
• Standardization of the DSMB process according to the charter and SOPs, 
• Enhanced collaboration and communication,
• 21CFRpart11-compliant electronic records and signatures management, 
• Real-time audit trail for future inspections,
• Better decision-making process

In summary, DSMBs and DMCs must follow GCP rules as described in the ICH E6 Good Clinical Practice (GCP) Guideline. GCP compliance ensures the protection of human subjects participating in clinical trials and guarantees that the clinical trial data are credible. However, GCP requirements are stringent and impose a high administrative burden on clinical teams. Adopting a validated electronic tool such as eDSMB® ensures the GCP compliance of DSMBs and DMCs while simplifying the work of clinical teams and committee members.

_________________________________________ 

¹https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-clinical-practice