Research Safety and Integrity

​Good Clinical Practice (GCP)

“Good clinical practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects.”

Compliance with GCP provides public assurance that the rights, safety and wellbeing of research participants are protected and that research data are reliable. Adherence to the principles of Good Clinical Practice is universally regarded as a requirement to the conduct of research involving human subjects. GCP training is required so that everyone involved in the conduct of clinical research are competent to perform their tasks, qualified by education, training and experience.

ICH-GCP lists down the responsibilities of the Investigators, IRB, and Sponsor and also provides standard guidelines on the following:

• Informed Consent
• Confidentiality and Privacy
• Participant Safety and Adverse Events
• Quality Assurance
• The Research Protocol
• Documentation & Record-Keeping
• Research Misconduct
• Roles and Responsibilities
• Recruitment and Retention
• Investigational New Drugs

MRC policies mandate that any researcher involved in human subject research at HMC should have completed the Clinical Trials Investigator (GCP) course available on the CITI site (www.citiprogram.org). It is the responsibility of MRC to ensure that all members of the study team have passed this module prior to participation in a study.

Data Safety and Monitoring Board (DSMB)

“A data monitoring committee (DMC) – sometimes called a data and safety monitoring board (DSMB) – is an independent group of experts who monitor patient safety and treatment efficacy data while a clinical trial is ongoing.” The DSMB will follow a Data and Safety Monitoring Plan. The DSMB will review whether the study data is being properly collected, analyzed, and reported, by whom and to whom, and how often. The DSMB makes its recommendations regarding continuing or stopping the study to the IRB and the study investigators.

When is a DSMB generally required?

• All Phase III studies require a DSMB, with the exception of low-risk behavioral and nutritional studies.
• For this discussion, "low-risk" refers to trials where subjects are expected to experience only minor side effects, and interim analyses are not crucial for the protection of the subjects
• The involvement of a DSMB may still be requested for low-risk studies if the studies are exceptionally large, long term, and/or involve vulnerable subjects
• Phase II clinical trials which are multicenter and randomized require a DSMB, with the exception of low-risk behavioral and nutritional studies
• Phase II studies which are "high risk" require a DSMB
• For this discussion, "high-risk" refers to trials of interventions associated with substantial side effects to subjects (e.g., side effects that could result in serious morbidity or death, or are irreversible), trials of diseases associated with high mortality or morbidity, and trials of highly experimental therapies (e.g., gene therapy)
• As a general guideline, DSMBs are needed for clinical trials of diseases with high mortality or morbidity, for clinical trials involving high risks, and for large, multicenter clinical trials
• For some studies involving particularly vulnerable study participants (e.g., children or persons with impaired ability to consent), it may be beneficially to utilize a DSMB as an additional measure of subject protection

Aside from these guidelines, do note that a DSMB may be set up for a study if requested by the institutional IRB.

How to set up a DSMB?

A DSMB is composed of at least three people (typically three to ten) who are not directly involved in the conduct of the study and have no financial links to the study. A DSMB will typically include an ethicist, statistician and medical personnel who specialize in the disease being studied and any possible adverse events (side effects) related to the experimental drug.

Reportable Adverse Events(AEs)

What are adverse events?

Adverse events (AEs) are events that involve physiological, social, economic, or psychological harm to subjects. These adverse events may also indicate risks of harm to additional subjects or others. AEs include expected and unexpected harmful effects, and unexpected harms of an interaction or an intervention. An essential element of human subject’s protection is identifying, analyzing the causes of, and responding appropriately to expected and unexpected adverse events, as well as unanticipated problems involving risks to subjects or others.

Reporting of adverse events

Regardless of whether the adverse event is determined to be an anticipated or unanticipated problem, the investigator must ensure that the adverse event is reported to a monitoring entity such as the Facility Director, Medical Research Center as well as the Institutional Review Board. Kindly refer to the policy for detailed information regarding reporting of adverse events.

Data and materials transfer

In the case of the transfer of sensitive information or biological samples from HMC to outside sites (collaborative or performance) a data share or material transfer agreement is to be in place. These are legal agreements (bailments) that govern the transfer of a tangible property between parties. This agreement would also detail the type of information transferred or the kind and quantity of samples transferred. The data or material transfer agreements need to be signed by representatives of both institutes. Aside from the HMC PI, DTAs and MTAs are signed by the Institutional Research Officer on behalf of HMC.

Animal care and use

As of now, HMC does not have an animal facility and hence studies involving animals may only be conducted in collaboration with institutes having animal facilities. In such cases a Data or Material Transfer agreement may be required. It is the policy of the Ministry of Public Health (MoPH) to require institutions to establish and maintain proper measures to ensure the welfare of all animals used for scientific purposes in Qatar. Animal experiments should be undertaken only after due consideration of their value to human or animal health or the advancement of knowledge on biomedical research weighed against the potential effects on the welfare of the animals. Projects involving animals must be based upon written proposals approved by an institution’s Animal Care Committee (ACC) which must take into account the justification for the project, the likely value of the knowledge to be gained, and the appropriate application of what is known as the 3Rs.

The 3Rs

The approach known as the 3Rs is to be considered at all times:

(a) Replacement of animals with other methods

(b) Reduction in the number of animals used

(c) Refinement of projects, procedures and techniques to improve the welfare of animals

Replacement: Alternative methods that replace the use of animals for scientific purposes must be sought and used wherever possible.

Reduction: Each project must use no more than the necessary number of animals to obtain scientific and statistical validity. The principle of reducing the number of animals used should not be implemented at the expense of greater suffering of individual animals. Scientific and teaching activities involving the use of animals must not be repeated unless essential for the purpose or design of the project.

Refinement: Animal species chosen must be suitable for the scientific activities, taking into account their biological characteristics, including behavior, genetic constitution and nutritional, microbiological and general health status.

The ultimate responsibility for ensuring compliance with the MoPH guidelines rests with the designated senior administrator responsible for animal use for the institution (e.g. CEO or Dean). Any project involving the use of animals for scientific purposes must be approved in writing by the institution’s ACC. Institutions that use animals for scientific purposes must implement processes that include:

(a) Establishing one or more ACCs. Where there is little use of animals for scientific purposes, institutions may consider accessing an external ACC or sharing an ACC with another institution

(b) ensuring, through the ACC and its Terms of Reference (TOR), that investigators and staff are aware of their responsibilities under the guidelines and that the use of animals for scientific purposes complies with the guidelines

(c) responding promptly and effectively to recommendations from the ACC to ensure that all care and use of animals remains in accord with the guidelines

(d) providing the ACC with the resources required to fulfill its TOR and responsibilities

(e) conducting an annual review of the operation of the ACC, including an assessment of the ACC’s Annual Report and a meeting with the ACC chairperson

(f) ensuring that there are adequate numbers of staff (a minimum of 2) to care for the animals and that those staff are appropriately trained and instructed

(g) Ensuring a high standard of animal housing and management is maintained over weekends and holidays (see Appendix I)

(h) ensuring that the appropriate veterinary services are available at all times and that there is access to diagnostic services

(i) Ensuring adequate record keeping and annual reporting