‘Patient diary cards and compliance charts can be considered as source documents’

Queries on GCP

A MONTHLY COLUMN BY Dr Arun D Bhatt

I have following queries related to Schedule Y.

a) Is it a must to take the investigator’s undertaking for currently ongoing study as per schedule Y?

b) Is it a must for Ethics Committee (EC) to give the approval as per the format of approval letter given in the revised Schedule Y? c) Is it a must to use a accredited laboratory (like NABL)?

d) Does the EC give comments on all SAEs, whether the SAE is related to study drug or not? Is it required to submit the comments to the DCGI?

e)Is it required to collect co-efficient of variations (standard error) for laboratory investigations? How can we co-relate the co-efficient of variation in statistical analysis if you have multi-centre study?

Suresh Vaghela

a) The new Schedule Y has come into force from January 20, 2005. Hence, it is not mandatory for trials approved prior to this date to obtain a new undertaking from the investigator. However, it is desirable to make the investigator’s aware of their responsibilities. As per the amended Schedule Y request them to comply with the conditions of the undertaking.

b) The EC approval should be as per the format in Schedule Y. However, the EC can add any additional relevant conditions as per the Indian Good Clinical Practices (GCP) and their standard operating procedures.

c) There is no mention of accreditation for laboratories used for generating data for clinical trials. Schedule Y insists that laboratories used for clinical trials should be compliant with Good Laboratory Practices (GLP). However, the animal studies should be conducted in an accredited laboratory.

d) At the time of reporting SAE, it is not possible to judge the causal relationship between the SAE and the drug. The response of the EC would depend on seriousness of the AE.

The EC will give prompt attention to an event such as death and will ask more information and provide comments. If the decision of the EC requires modification of protocol or suspension/termination of the trial, the DCGI’s office must be informed.

e) If you use multiple laboratories in the trial, it would be difficult to pool data unless all of them use the same method for lab analysis. You will have to consult an expert statistician who is aware of GLP guidelines for such issues.

A subject, who was withdrawn from the study due to an SAE, wants to participate in the same study voluntarily. Is it necessary to repeat the consent procedure or to make him sign again on the same consent form?

Hiren Thakkar

If the subject withdraws due to an SAE, it is not ethical to take him in the same study again, even if he is willing.

Can patient diary cards and medication compliance cards (both paper based) be considered as source documents (SD) and retained at the investigator site?

Rajiv Maini

Patient diary cards and compliance charts can be considered as SD. However, this should be documented in the protocol and agreed between sponsor and the investigator. A source data list should be produced, signed by the investigator and filed at site. If patient diary cards and/or compliance cards have not been identified as source documents in the protocol, a file note documenting them as source documents can be prepared and filed at the site and in other relevant sponsor files at the time of study initiation.

However, this should be signed and agreed by the investigator and sponsor. (Also please see general discussion on SD in the January 05 GCP QA in Express Pharma Pulse).

We are in the process of generating quality systems with respect to clinical research. Now, as I learn from the system, having a quality manual and quality policy is also essential as per ISO: 9000-9001. How does one generate a quality manual?

Deepti Dua

Please refer to ISO 9001:2000 standard, particularly section 4.2.2 Quality Manual and 5.3 Quality Policy. While preparing quality manual, you have to keep in mind about the ‘‘mandatory procedures’’ and ‘‘mandatory records’’.

It would be desirable to attend a course on ISO and to consult your corporate/manufacturing quality control department for guidance.

Dr Arun D Bhatt, well-known clinical pharmacologist from Mumbai, and currently president, ClinInvent Research India Pvt Ltd, answers your questions on Good Clinical Practices. Please send in your questions at: arunbhatt@clininvent.com