Ethics Committees (ECs) constitute the third arm of the research triangle and it can make significant contribution towards the ethical conduct of clinical trials. EC ensures a competent review of all ethical aspects of the clinical trial proposals received and reviews the same free from any interest and influence that could affect their decision. Specially post 2005, i.e. after Schedule Y has been amended, obtaining ethics committee approval is one of the mandatory steps towards conduct of the trial. With so much importance given to ECs, we still have a question to ask the institutions. Are these committees trained enough to take up such a challenging role? Do we have trained personnel within the committee who can take a fair decision of approving or disapproving a trial? While amended Schedule Y, ICH-GCP guidelines, Indian GCP specifies standards to be maintained for EC, majority of institutions in India still lack compliance with the applicable standards in true sense.
Frequency of meetings
As per Schedule Y 2005, 'every IEC should have its own written SOPs according to which the committee should function. The SOPs should be updated periodically based on the changing requirements.' As the matter of fact, none of the ECs have clear-cut guidelines on the reasonable time frame for EC meetings. At most of the places, the meeting often takes place on an ad hoc basis as and when the need arises. In large institutions, the frequency of meetings varies from once in a month to once in 3 months whereas private institutions meet every now and then based on the need. In both the scenarios, it is difficult to do justice with the review process. Furthermore, there are some institutions which have a two step 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 benefit. Also this delays the timelines, unnecessarily the dirty business of blame game starts at sponsors, CROs and investigators etc.
Solution
In author's opinion, the most practical solution is to have a procedure to conduct a meeting once in a month, if due to some reason, the meeting does not take place, there must be a solid reason for it and it should be approved by the chairperson. With respect to the two tier process, members from both the committees can be combined to frame an EC which can review the project as a whole.
Amendments
We all understand that there might be changes in the study documents after the EC has approved the protocol, i.e. there could be minor (for example: logistical change i.e. lab address change, CRO address change, rewording of sentences etc) or major amendments (for example change in selection criteria, number of patients, safety or efficacy parameters) in the protocol and none of the EC that we have worked so far have clear procedures with respect to the amendments.
There are some institutions in which minor amendments go as notification whereas in others, minor changes (non-substantial) in the protocol or study documents are discussed in the regular meeting which takes its own time to convene. Sometimes, due to non availability of quorum members, meeting does not take place. As a result, one has to wait for a full fledged meeting which may occur once in 3 months for minor changes which even has no impact on the safety and efficacy of the trial.
Solution
All minor amendments should go as notifications to the ECs. A summary of amendments shall be prepared by the applicant mentioning the change done in the relevant sections and the reason for change. This summary along with the amended documents should be submitted to the member secretary and the documents shall be notified. The trial should not be stalled till EC gives its decision. In case of substantial amendments, which may affect the safety and efficacy of the subjects participating in the trial, an applicant has to submit the documents in the same way as above and then wait for the meeting to hear the decision. The entire procedure shall be clearly laid down in the SOP of ECs and it is sponsor's duty to clarify all the above points during the pre selection site visit.
Composition
Amended Schedule Y and ICH-GCP guidelines clearly mention the composition and quorum requirements. Till date, at majority of institutions, the chairperson is from within the institution. This is in contrary to Schedule Y which clearly states that chairperson has to be from outside of the institution. Furthermore, there is till no clarity on the number of members required for quorum, meaning and importance of a lay person. The roles and responsibilities of each member are also not clearly defined. For example member secretary acts as authorized signatory in some institutions whereas in others, member secretary has no specific role to perform.
Solution
In author's opinion, the EC members at most of the institutions are not offered any kind of training. Due to lack of training, EC members are not aware of regulatory guidelines and operational procedures. It is mandatory that all EC members are trained as an ongoing process on ICH-GCP guidelines, Schedule Y, Indian GCP, ICMR, Declaration of Helsinki, WHO guidelines.
Standard operating procedures (SOPs)
As per Schedule Y, ICH-GCP, ICMR and Indian GCP guidelines, it is mandatory for all ECs to have their written procedure or SOPs. As per current scenario, in majority of the institutions, the SOPs are not existing and even if the document is present, it doesn't contain the basic elements like documents to be reviewed, number of copies required, membership criteria and quorum requirements, frequency of meetings, submission deadlines, expedited review process, document control system, record retention and archival procedures etc. It has been generally observed that ECs are reluctant to provide the SOPs to the sponsors/CROs during the site evaluation visits and this leaves all the parties in a situation of ambiguity whether to believe the investigator who has given the information about the EC of his institution or not. In all this, the investigator has to cut a sorry figure and the decision of site selection may go against him/her.
Solution
ICMR provides the templates for writing SOPs for ECs. All ECs should appoint a quality assurance person (this may be an internal member or an external person who carries out quality assurance for the EC) to check out these activities. There is no need for ECs to prepare a bulky document of 100 pages, instead a simple 3-4 pages document stating the basic elements should suffice provided it is prepared, discussed, approved and authorized by an appointed team within the EC members.
Document of EC approval
After review, the EC issues an approval letter. This document invariably contains errors and has to be quality checked by the sponsor/CRO after receipt. Following are the types of errors which are mostly found in the approval letter.
● Not stating correct version numbers of the documents reviewed
● Incomplete list of EC members present/absent during the review process
● Date of review and date of approval wrongly given
● Format not as per Schedule Y.
● Wrong protocol title given
As a result, it becomes burdensome for the applicant to keep communicating this to the investigator, then send it for correction, obtain a modified document then resend it for further changes etc. All these activities unnecessarily take time without adding any value to the task.
Solution
After the EC approval document is ready, it becomes the EC members (especially member secretary and chairperson) responsibility to quality check the document before its release. A checklist of basic elements should be made at their end and the document should be checked against the same. Ultimately, it is the quality that matters. A good quality work speaks about the type and functioning of EC.
EC submission fee
Last but not the least, there is no consistency and uniformity in the submission fees across ECs in India. In government institutes, the fee may be on a lesser side, ranging between Rs 5,000-20,000 whereas, majority of private/independent ECs are charging a fee in a range of Rs 20,000 to as much as one lakh rupees. There is absolutely no justification of any kind that can be provided by anyone for charging such a high amount by the committee. Since the applicant is at the receiving end, so not much option is left with them but to pay this amount and push the trial.
Solution
Charging fee is not a wrong practice. But it should be nominal and mentioned in their written procedures. All private and government institutions should be in sync with each other and to the best possible extent, should have uniformity and consistency in this process.
The author has made an attempt to highlight the issues which are generally faced by the sponsor/CRO and the hardships one goes through in this process of EC submission. The solutions provided here may not suit all the ECs but at least this will give institutions a food for thought and they will definitely step forward towards in streamlining the entire process to the best possible extent. Currently, DCGI fully depends on ECs for implementing ethical standards in clinical trials but there is absolutely no direct linkage of any kind between the DCGI and ECs. It is very much important the DCGI and ICMR join hands and take some concrete steps towards inspecting ECs in India on a regular basis. It's time now that individual ECs take ownership and act to contribute towards ethical conduct of clinical trials. Pharma industry has been and will always be ready to extend the helping hand in working towards improving the quality and working of ECs in India.
(The author is a clinical research professional)