According to the amended Schedule Y of Drugs & Cosmetics Act (IInd amendment), 2005, the number of persons in an Ethics Committee should have at least seven members. Ethics Committee should appoint, from among its members, a Chairperson (who is from outside the institution) and a Member Secretary
Ethics Committee (EC) is an independent body constituted of medical/ scientific professionals and non-medical/ nonscientific members, whose responsibility is to ensure the protection of rights, safety and well being of human subjects involved in a trial.
EC ensures a competent review of all ethical aspects of the project proposals received and executes the same free from any bias and influence that could affect their objectivity. It might have different names at different institutions but the prime responsibility remains the same. EC is also known as:
*Independent Ethics
*Committee (IEC)
*Institutional Review Board (IRB)
*Ethics Review Board (ERB)
The chief responsibilities of EC are:
1. Approval / Permission for the conduct of clinical trials
2. Review of progress
3. Regulatory Compliance
1. Approval/Permission for the conduct of clinical trials
No clinical trial should be initiated at any investigator site without obtaining a written approval/permission by the respective EC. In order to grant approval/permission for a trial proposal, EC reviews the following document:
*Protocol (for scientific rationale)
*Informed Consent document (for the safety and welfare of research subjects)
*Informed Consent document's translation(s) in patient's native language (for protecting the rights of research subjects)
*Investigator Brochure for all relevant clinical and non-clinical data on the investigational product
*Grants & Payments (as per institutional policy)
*Study Advertisement (if applicable)
*Investigator's Qualification
*Trial permission from Drug Controller General of India (DCGI)
Only after review of all the applicable documents during the scheduled meetings EC either approves (full or conditional) or disapproves any trial proposal. Any amendment(s) to the approved trial documents (protocol & informed consent document) requires a fresh approval by the EC.
2. Review of Progress
After granting the approval it is the responsibility of EC to have an ongoing review of the trial progress. This includes but is not limited to:
*Review of safety reports (all the serious adverse events and adverse drug reactions happening at the trial sites)
*Review and approval of the amendment(s) in protocol or informed consent document.
*Review of significant deviations or violations (if any)
The frequency of these reviews may vary from institute to institute as specified in the respective EC charter or standard operating procedures.
3. Regulatory Compliance
In order to comply with all the applicable regulatory requirements and guidelines each EC is required to have the following records:
*Written standard operating procedures or charter
*Constitution and composition of the EC
*The curriculum vitae of all EC members
*Copies of all the trial(s) documents received for review
*All the correspondence between EC and investigator
*Agenda & minutes of all EC meetings
*Final report of all the studies approved by EC
The ethical review should be done through formal meetings and should not resort to decisions through circulation of proposals.
As on date a number of guidelines are available on the composition & functioning of EC. Though the basic essence of various guidelines remains the same there are minor procedural differences. These differences becomes specially important while conducting clinical trials in India as one needs to comply with all applicable standards and guidelines. In addition to International Conference on Harmonization-Good Clinical Practice Guidelines (ICH-GCP) of 1997, Schedule Y of Drugs & Cosmetics (IInd Amendment) Rules, 2005 issued by Ministry of Health & Family Welfare governs the conduct of clinical trials in India.
According to the amended Schedule Y of Drugs & Cosmetics Act (IInd amendment), 2005, the number of persons in an Ethics Committee should have at least seven members. Ethics Committee should appoint, from among its members, a Chairperson (who is from outside the institution) and a Member Secretary. Other members should be a mix of medical/non-medical, scientific and non-scientific persons, including lay public, to reflect the different viewpoints.
For review of each protocol the quorum of Ethics Committee should be at least 5 members with the following representations:
(a) Basic medical scientists (preferably one pharma-cologist)
(b) Clinicians
(c) Legal expert
(d) Social scientist/ representation of non-governmental voluntary agency / philosopher / ethicist / theologian or similar person
(e) Lay person from the community
In any case, the ethics committee must include at least one member whose primary area of interest/ specialization is nonscientific and at least one member who is independent of the institution / trial site. Besides, there should be appropriate gender representation on the
Ethics Committee. If required, Subject experts may be invited to offer their views. Further, based on the requirement of research area, e.g. HIV AIDS, genetic disorders etc. specific patient groups may also be represented in the Ethics Committee as far as possible.
Only those Ethics Committee members who are independent of the clinical trial and the Sponsor of the trial should vote / provide opinion in matters related to the study.
While the amended Schedule Y of Drugs & Cosmetics Act, ICH-GCP Guidelines, Indian GCP Guidelines& ICMR Guidelines specifies a set of standards to be maintained for EC, majority of hospitals in India still lack compliance with the applicable standards in true spirits. The major areas that requires immediate attention & correction include:
1. Composition & 'quorum' requirement: Though the guidelines are clear on what should be an ideal composition of EC it is still not appropriate at majority of places. There is still a dilemma whether the Chairperson has to be from outside of the institution or not. Even where the composition is appropriate meeting of quorum requirements during each review is a challenge and often research projects are reviewed & approved in the absence of non-science member (lay person). All such EC approvals that do not comply with the regulatory requirements are invalid and inappropriate and could lead to regulatory consequences on a later date.
2. Written Procedures or Charter: Written procedure or charter of EC is required by all the guidelines. These are either not existing at all or does not include the required elements such as essential review documents, membership criteria, frequency of meetings, submission deadlines, circulation of review documents, review process, quorum requirements, voting process, expedited review process, version control, safety review process, criteria for ongoing/annual review, document tracking, storage, accessibility & archival etc. Often the written procedures are not provided to Investigator(s) or Sponsor(s) leading to a situation of ambiguity.
3. Frequency of meetings: There are no clear-cut guidelines on what should be a reasonable time frame for EC meetings. The arrangement is quite ad-hoc at majority of places leading to meeting taking place on need basis. While the EC in big governmental/ regional hospitals meet quite infrequently (4-6 times a year), the private hospital EC meets on as and when basis. In both the cases it is difficult to do justice with the review process as either the time for review is too short or the number of projects in a single review meeting is too large. The infrequent EC meetings at big governmental/ regional hospitals delays the overall project timelines which in turn prolongs the time to market a potentially beneficial drug for the man-kind. Most of these governmental/regional hospitals are really big and multi-specialty in nature leading to accumulation of a large number of research projects to be reviewed in a single EC meeting. Further, if EC proposes an amendment in any essential trial document it gets an opportunity to be reviewed only in the next meeting.
4. Scientific review vs ethical review: Some of the big research institutions/hospitals employs a two-tier review process where the research projects are first reviewed and approved by a Scientific Committee followed by review and approval by EC or vice-versa. This at times creates a lot of confusion and duplication of efforts without any perceived benefit. Members from both the committees can be combined to frame an EC for holistic review of trial projects.
5. Initial & ongoing training of EC members: Though EC member at majority of hospitals are highly competent & experienced professionals, however no initial or ongoing training is offered as a standard practice. The important training topics for EC members include training on:
*Drug Discovery & Clinical Trial Process
*ICH-GCP Guidelines
*Additional Guidelines on EC (Schedule Y, Indian GCP, ICMR, Declaration of Helsinki, WHO guidelines etc.)
*Written Procedure/ Charter of EC etc.
Due to lack of training EC members themselves are not aware of regulatory guidelines and operational procedure/charter at times.
6. Document receipt, tracking, circulation, review, storage & archival: Although majority of hospitals & research institutions specifies the type and number of copies of essential documents to be submitted to them for review, there is no audit trail on their receipt, tracking, circulation, review, storage & archival. This in turn is raising issues on data privacy as well as data availability in a right fashion and at right time. Often it is difficult to link various documents submitted for a project at different times as they are rarely filed in a single file bearing a tracking number that connects it to a Master Tracking Log. Ideally each research project that comes for EC review should be assigned a tracking number and the same number should be used for all future communications. A Master Tracking Log should list all the tracking numbers along with the location of the respective file so that the project files can be located easily and all the documents pertaining to one project can be filed in the same file.
7. EC approval document: The approval document issued by EC for a particular project requires major amendments at majority of places. The same does not specifies the documents reviewed for a particular project along with the version number and date, issues raised during review process, list of EC members present/absent during the review process and the obligations of the Investigator as laid down by the EC following the approval of a research project.
Most of the issues raised above are absolutely mandatory for an EC to be really ethical. In this era of Evidence Based Medicine when more and more number of clinical studies are being conducted to establish the safety and efficacy of any new drug, a strong functioning and vigilance of EC is required to protect the rights & safety of study participants.
Apart from Sponsor(s) & Investigator(s), EC(s) constitute the third arm of the research triangle and it can make significant contribution for the ethical conduct of clinical trials. A number of organizations have come up in India that imparts training to EC members. Its time now that individual EC(s) takes this ownership and act to contribute towards ethical conduct of clinical trials in India.
(The author is director, clinical operations & QA, Catalyst Clinical Services Pvt. Ltd.)