Any research into human subject need to be approved by whatever committees are required by:

1. Your country’s legal requirements
2. Your institutional requirements
3. Your funder’s requirements
4. Your collaborator requirements

Typically this is review by an institutional Review Board or a scientific review committee followed by review by a local or national Independent Ethics Committee (IEC), which is an independent body responsible for ensuring the protection of the rights, safety and well-being of human subjects involved in a trial.

Usually the institutional review will ensure the science is valid, that the study is safe and also consider administrative, operational and financial issues such as whether the study will impact on others programmes, if there is the appropriate staff capacity and whether or not the finances are in order.

The ethics committees review the integrity of the protocol, because poorly designed studies that are either not needed or cannot answer the question are unethical. They then also give a close review of the ethical and safety aspects of the trial. They do this by reviewing, approving and providing continuing review of the trial protocol, amendments, methods and material used in obtaining and documenting informed consent.

Ethics Committees comprise a number of members, who collectively have the qualifications and experience to review and evaluate the science, medical aspects, and ethics of the proposed trial.

ICH GCP recommends that the EC should include:

• At least five members.
• At least one member whose primary area of interest is in a non scientific area.
• At least one member who is independent of the institution/trial site.

Only those EC members who are independent of the investigator and the sponsor of the trial should vote/provide opinion on a trial-related matter.

The EC should have a SOP to which they work, and maintain written records of its activities and minute its meeting.

How to submit to a Regulatory or Ethical Review Board

Prior to commencing a clinical study, a number of core documents should be submitted to the authorities for review. They include but are not limited to:

• Covering letter
• The study protocol
• The Investigator Brochure – if it is an unregistered product
• All informed consent forms, including translations to local languages and back translation reviews if appropriate (for information on achieving this, see: http://globalhealthtrials.tghn.org/articles/back-translation-clinical-trial-documentation-informed-consent-forms/)
• CV of the Principal investigator – in some cases
• Data Collection Forms, Case Report Forms, Patient diaries, etc.
• Patient recruitment materials
• Any information about payments or compensation to the patients
• EC Fees – if relevant

Various countries have different ways of convening their Ethics Committee to ensure patients enrolled in clinical trials are protected. In the EU, EU directive which incorporates the roles and responsibilities of all participants in a clinical study including the EC are now included in each member state law.

In many countries it is possible to submit to the Ethics Committee and regulatory authorities in parallel. In others such as Russia, submission should be made to the Ethics Committee who will review the application and, once approved, the regulatory review process will take place.

Other countries have a National Ethics Committee who review and approve clinical trials on behalf of participating sites. They are usually well-structured and established, and help to provide general oversight of the ethical issues involved in the trial. They may want to check that patients are not unnecessarily excluded from the study or may need justification as to why vulnerable patients are recruited to the study unnecessarily.

Once approved, the trial is then reviewed by a local EC (which is often linked to the trial centre). They will review the study documents and comment on ethical issues that may affect patients locally. For instance they may want to know if the Informed Consent Forms are translated in all the languages spoken locally, and how this was achieved, or that patients travelling to study visits will be compensated for their travel expenses. Examples of countries that have the two-tiered ethical review process include the UK, Italy, Belgium etc. Countries such as the Philippines have a single review process by the local EC.

Following submission to the EC, the committee will review the documents within a reasonable time and share its views in writing. The EC may request additional documentation when, in the judgement of the EC, the additional information will help the committee reach a decision. They may also convene a sub-committee if they feel that the main EC has limited experience or expertise in the subject area.

In many countries, the review process and timelines for review are published. Many countries stick to the review timelines while others do not, but this might not be apparent until after the review process. Once the review process is complete, the EC will arrive at 3 major decisions:

• approval/favourable opinion;
• modifications required prior to its approval/favourable opinion;
• Disapproval / negative opinion.

During Study Conduct

Once the study is ongoing, the EC may conduct continuing review ongoing studies at intervals, appropriate to the degree of risk to human subjects, but at least once per year.

The sponsor and investigator will also need to inform the Ethics Committee of any

modifications to the protocol. Any substantial amendment to the protocol would need to be submitted before implementing (unless they were required to protect the safety of the participants. Substantial amendments are anything that impacts the patients or the outcome of the study, so any changes in numbers to be recruited, the inclusion/exclusion criteria, any assessments, methods or intervention changes, for example).

Minor changes need to be submitted as a notification or and administrative change

Conclusion

The role of the regulatory review of clinical studies is to determine the integrity and value of the research and to protecting the rights of the participants.

For more guidance about ethics, visit the Global Health Network’s bioethics member area, www.globalhealthbioethics.org.

To learn about the processes involved in reviewing a protocol for regulatory/ethics boards, visit the Reviewer’s member area of the Network, www.globalhealthreviewers.org.

For a database of regulatory requirements for LMICs for different study types, visit: http://regulatory.ghtcoalition.org//

References

EC directive

http://www.eortc.be/services/doc/clinical-eu-directive-04-april-01.pdf

The Global Health Regulatory Requirements Database is designed to help researchers and regulatory affairs professionals access the information they need to develop effective strategies for gaining approval to conduct clinical trials and market products. The database provides high-level information on regulatory requirements, timelines, costs, and other basic information required to create product development plans for new tools.  http://regulatory.ghtcoalition.org/

Global Health Reviewers (www.globalhealthreviewers.org) is the arae of the network which supports those reviewing protocols in ethics committees and IRBs. On the site you will find free and open access pragmatic guidance on how to review different types of protocols, as well as up to date news and guidelines.