Phase 1 trials are usually conducted in healthy volunteers to assess safety, tolerability and pharmacodynamics. Only for carcinogenic drugs, end stage disease, lack of other options, patients will be used in the phase 1. Recently I read in the news that some companies got approval to conduct phase 1 study in diabetic patients. Based on what scenario, they got regulatory approval for phase 1 patient study?
Divya
EMEA Guidance on first-in-man suggests that such studies can be done in either healthy subjects or patients. The decision depends on several factors outlined below:

4.4.2 Protocol design

4.4.2.1 Choice of subjects for first-in-man trials with high-risk medicinal products

One of the main purposes of a first-in-man trial is to assess tolerance and subjects are not generally expected to derive any therapeutic benefit. The paramount factors should always be the safety, rights and well-being of the volunteers, whether patients or healthy individuals, and the value of what can be learned from the clinical trial.

The choice of the study population for high-risk medicinal products, i.e. healthy subjects or patients, should be fully justified by the sponsor on a case-by-case basis. Several factors should be considered, such as (a) the risks inherent in the type of medicinal product, (b) its molecular target (c) immediate and potential long-term toxicity, (d) the presence of the target in healthy subjects or in patients only and (e) the possible higher variability in patients. Concurrent medication in patients may give rise to the potential for interactions with the possibility for adverse reactions and/or difficulties in the interpretation of results. The sponsor should also consider whether any effects that may be seen in the population of choice are indeed relevant and can be extrapolated to the intended clinical application. Special considerations should be given to potential long-term consequences on physiological systems and potential long-term safety problems.

If the study is approved by DCGI and independent ethics committee, but the investigator is willing to undertake the study at the institution then is it necessary to take the permission of the dean of the institute?
Shruti Kulkarni
If the investigator wishes to conduct the study at the institution, he should take approval of institutional ethics committee. See Schedule Y.

Clinical trial on a new drug shall be initiated only after the permission has been granted by the Licensing Authority under rule 21 (b), and the approval obtained from the respective ethics committee(s). The Licensing Authority as defined shall be informed of the approval of the respective institutional ethics committee(s) as prescribed in Appendix VIII, and the trial initiated at each respective site only after obtaining such an approval for that site.

If the institution policies require that permission of Dean is required, he should obtain the permission.

If a study protocol has been approved for version 2 from DCGI and EC of the site and version 3 have come out before the study start up. Can we initiate the sites based on ver 2 approval?
Secondly, if yes then on what basis will be patient enrolled, on ver 2 or ver 3. ( ver 3 submission done, not approved). Ver 3 contains changes in study schedule and inclusion and exclusion criteria.
Ajay Vats
DCGI office has classified protocol amendments in three categories:
a. Those amendments which do not require notification to or permission of the Licensing Authority

■ Administrative and logistic changes

■ Minor protocol amendments and additional safety assessments in case the institutional ethics committee has already approved these changes

b. Those amendments which require notification to the Licensing Authority but need not wait for permission

■ Additional investigator sites

■ Change in investigator with the consent to withdraw from the earlier investigator

■ Amended investigators brochure, amended informed consent

■ Those amendments which require prior permission of the Licensing Authority

■ Additional patients to be recruited

■ Major changes in protocol with respect to study design, dose and treatment options

■ Any change in inclusion or exclusion criteria

Since version 2 is approved by DCGI and EC, that's the version to be used for consent and enrolment. Version 3, which has changes in selection criteria and visit schedule, will need EC and DCGI approval before it can be used.




Dr Arun Bhatt is currently,
president, ClinInvent, Research Pvt Ltd, Mumbai.
Readers can send their queries at: arunbhatt@clininvent.com