Transfer of patients may not be a common practice

Dr Arun D Bhatt

In a multi-centric and centrally randomised phase III trial, can a patient enrolled in one of the sites be transferred to another site in the middle of a trial realising a clear cut geographical advantage for the patient. As far as treatment is concerned, patient can get similar treatment from another site. What are the implications from the GCP angle? Is it a practice that referral centres transfer patients in the middle of a trial to the regional centres very often?

Umakanta Sahoo, Mumbai

There are several implications, which are discussed below: Ethics Committee (EC) of the site where patient was first enrolled (site 1) is responsible for overseeing the safety of the patient. If the patient is transferred to another site (site 2), you will need to inform EC of site 1 about the transfer of the patient.

The EC can ask the reasons for the transfer and you will need their written agreement/ approval for this action. You will also need approval of EC of site 2, as they will have to take responsibility of the transferred patients safety. This process is likely to take quite sometime as EC usually meets as per their schedule.

This means that the patient has to continue the follow up visits at site 1 till both ECs have given their agreement/ approval. This will also apply to SAE reporting.

If this practice is to be followed for all patients with geographical advantage, you will have to amend the protocol & obtain EC and Regulatory approvals.

Drug accountability and Randomisation: If the trial is centrally randomised, it would be difficult to manage randomisation, drug supplies and drug accountability at site 1 and 2. Financial payment to investigators for the patient and source data verification at 2 sites will be other major issues. However, the most critical issue is viewpoint of auditors and Regulatory inspectors. There is an US FDA warning letter (Sep 27, 2000) issued to an investigator (Courtesy: Dr Tanuja Kulshreshtha Amdavad).

The relevant excerpt is given below:

Dr Jeffery R Levenson, MD. The Research Consortium Inc., 9303 Seminole Boulevard Florida.

Page 4 under ‘‘summary of violations related to requirements for investigator reporting to IRB (21 CFR 312.66)’’

You did not report to IRB changes in the research activity and unanticipated problems involving risks to human subjects or others, and made changes in the research without IRB approval for example:

You did not obtain IRB approval for continuing study based activities at neighbouring hospital or nursing homes (secondary institutions) to which subjects were transferred after their enrolment at the — for the — general hospital —. We note that you did not seek IRB approval for continuing research at secondary institution even after IRB specifically informed you that they could not continue to serve as the IRB to the second institution. Instead you incorrectly informed the IRB that secondary institutions were only providing ‘‘incidental care’’ and were not research sites, when in fact you were conducting research on subjects and collecting data at these institutions.’’

In view of the above issues, transfer of patients in middle of the trial from site 1 to 2 is unlikely to be a common practice. If geographical location is an issue, the patient should be referred to the Centre in other city before screening, as the address would be known at that time!

In Indian scenario, where patients and their legally acceptable representatives are being given Informed Consent Form (ICF) translated into regional languages, which they are signing in the regional language, does one still need an impartial witness?

Pari Sharma, Delhi

Impartial witness is not needed if both the patient and his legal representative are literate and can sign the ICF in their language.

Can the Principal Investigator delegate the duty of measuring blood pressure and recording on the source notes to a study team member who is not a physician?

Pari Sharma, Delhi

Yes. If he/ she can demonstrate and document, that the person who is given the task has received such a training. Nurses do take BP in intensive care units and hospitals. If BP is an end point for efficacy/ safety, it is advisable to delegate this function to a physician. Even for bioequivalence studies, some sponsors insist that a physician should measure pulse and BP.

If one were using the traditional method of randomisation (based on randomisation list generated by data management and not IVRS) and If there are two requests for randomisation from the investigator almost at the same time (within a gap of 1 min), but the date of consent of the subjects to the trial are different and they have been found eligible after screening on the same day then how should one go about randomising the subject?

Pari Sharma, Delhi

Although the dates of consent are different, as the randomisation is on the same day, one would first randomise the patient, whose request came 1 min earlier.

Can an investigator/ sponsor collect back the patient information sheet (PIS) after the patient has signed the informed consent form? Can this be done? There is a possibility that the local media may misuse this information. For example there may a mention of the risk or suicide in the PIS of an antidepressant or a mention of a possibility of bone marrow depression.

Dr Vijaya Jaiswal, Amdavad

As per ICH-GCP, PIS is the written information for the patient. Even the ICF has to contain description of reasonably foreseeable risks or inconveniences to the subject. So the information about which you are worried is any way in informed consent forms. Besides, any one can find out list of side-effects, if it is a drug already on international market.

Dr Arun D Bhatt, well known clinical pharmacologist from Mumbai,
and currently president,
Clinical Development,
Chembiotek Research International Pvt Ltd answers your questions on Good Clinical Practices. Send in your questions at: arun_dbhatt@hotmail.com. All queries should ideally reach him by the 15th of each month.