How to get DCGI NOC without query

Though no official guidelines have been published CROs and Sponsors have been receiving deficiency letters from DCGI. We depict some important points to be kept in mind while drafting protocols, ICF for clinical trials and the supportive documents that should be provided along with DCGI NOC application so as to obtain DCGI NOC without queries.

Due to recent uproar in Indian parliament over the credibility/safety of clinical trials conducted in India and concern over the people exposed to drugs, DCGI of late has been cautious over providing NOC for clinical trials in India. For the records, 250 clinical trials were approved by DCGI during 2010, but the same over a period of six months during this year (2011) stands at 25. There have been reports of non intimated deaths and declined compensation to subjects for various trials held in India.
Though no official guidelines have been published CROs and Sponsors have been receiving deficiency letters from DCGI. we depict some important points to be kept in mind while drafting protocols, ICF for clinical trials and the supportive documents that should be provided along with DCGI NOC application so as to obtain DCGI NOC without queries.

Study Related Injury and Compensation:

As the concern is more on study related injury and compensation, please ensure that these areas are addressed as per ethical guidelines and Indian regulatory requirements in appropriate sections of your protocols and ICF's.

Study Related Injury:

The onus on study related injury will be with the organisation that's applying for NOC. If the application is delegated through a CRO by the sponsor then statements should be mentioned in appropriate sections of the protocol and ICF that In case of study related injury {CRO Name} will provide complete medical care along with compensation for injury. If NOC is applied through sponsor, then the sponsor should take the responsibility of study related injury and compensation.

Compensation:

As feedbacks reveal that the subjects/patients are not compensated proportionately for their participation in the trial you are requested to add the following statement in protocol and ICF, Compensation for participation in the study will be paid proportionately at the end of each period of the study.

Age limit:

As the probability of getting an insurance reimburisement in the event of death/disease decreases with ages beyond 45 yrs, (you are required to undergo a medical test with the insurance agency designated doctor, if you are above 45 years of age) the agency now wants studies to be performed with subject within an age limit of 18 - 45 yrs both inclusive. Note: A thorough literature research should be done before deciding on the same. If a different range is desirable (e.g. safety issues) the same should be communicated to the regulatory authorities with supportive data.

No of Subjects:

Sponsors/CROs should provide proper justification for the number of subjects to be recruited for the trial. Though this should be justifiable for a clinical trial its not the same with bioequivalence study. If you are proposing a subject size of more than 50 for a bioequivalence study, you are sure to get a query to justify the same. This is fair, as a subject size of 40 should be more than sufficient to prove bioequivalence with sufficient power for a non highly variable drug. A higher number of subject number for a bioequivalence study, may raise doubts of forced bioequivalence at the cost of drug exposure to subject. If you are to include subjects more than 50 for any study it's advisable to provide proper justification for the same with ISCV from pilot data or with reference to published literature. If you are skeptic about your pivotal fortunes you may propose an arbitrary sample size in pivotal protocol and mention that the sample size will be finalized based on pilot study results.

IEC Approval:

The DCGI now wants the active participation of IEC/IRB in the NOC process of the trial. As per new requirement only IEC approved protocols should be included in application of DCGI NOC. All ethical committees (if formed as per regulatory requirements) will have a doctor/lawyer/Layperson/Scientist in place as its members. DCGI feels that the IEC would have thoroughly reviewed the protocol and if any issues relating to safety of subjects were present, objection would have been raised and deficiencies resolved before IEC approval of the protocol.

IEC Approval Process:

All the documents with respect to IEC application, composition and approval should be enclosed. The minutes of the IEC meeting should be documented along with the DCGI NOC application. This will give a brief idea to DCGI about objections raised with regards to protocol and ICF if any, and the resolution of the same before approval.

Methods used to recruit volunteers for the study:

During IEC approval CROs are to provide the details of methods used for volunteer recruitment for that study, which includes but are not limited to advertisements, hand outs etc. DCGI has now made it mandatory to provide the same during NOC application so as to scrutinize for any fiddling claims to woo the subjects into the trial.

Informed consent process followed for the study:

Sponsors/CROs are to provide the informed consent process that will be followed during the study. They will have to submit the ICF forms to be used in the trial along with NOC application. Presentations and questionnaires that will be provided to the subjects during the Informed consent process are also to be provided during the NOC application. Note: Many CROs are providing their SOPs on volunteer recruitment, Informed consent process and IEC approval process for the requirements Nos. 5, 6 & 7 discussed above. But it's not as
• The same SOPs would have been audited by the DCGI during CRO facility approval.
• The same documents would be recycled for all NOCs applied through that CRO, which is quiet ridiculous.
We strongly recommend providing the documents as discussed above to avoid any queries from DCGI.

Note: This is first in series of articles on instructions to get DCGI NOC without query. The Other basic requirements for DCGI NOC application has been provided in this article titled Documents to be submitted to DCGI for grant of BE NOC