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  • Tamara
    19/07/2017 15:09
    Hi, we have a question regarding who should be considered a ‘sub-investigator and linked to that who should be entered in Field 6 (‘names of sub-investigators’) on the FDA 1572 form, regardless whether we should or shouldn’t collect the form in Europe. Both GCP (1.56) and FDA regulations (21 CFR 312.53(c) state that the sub-investigator is someone at the site who will assist the investigator in the conduct of the investigations under the supervision of the investigator. Mainly these are significant contributions. So both confirm (as do some of the previous discussions here on the RQA forum) that non-physicians can be sub-investigators (as long as they do not take trial-related medical decisions). Also the FDA 1572 guidelines state that Field 6 is to capture information about individuals who, as part of an investigative team, will assist the investigator and make a direct and significant contribution to the data. However, so far it is usually the physicians who are delegated to be the study’s sub-investigators, while in many cases it is the study nurse, who performs the study (though of course does not make the medical decisions). However, I have not (yet) seen any comments on this during audits. Is this not something that should come up during audits? And is there a trend towards having non-physicians as sub-investigators? Thanks.
  • GCP Com
    19/07/2017 17:44
    You are correct that this is something that should come up at audit, as it is frequently cited in inspections findings.>> It is a good idea to look at the RQA GCP Q&As on this website. See Question - "Who should be listed on the delegation of responsibilities log?">> Is this a question of definitions?>> ICH E6 1.56 defines Subinvestigator:- "Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows)". So it is best to ask the question the other way round; which individual members of the clinical trial team (designated and supervised by the investigator at a trial site) perform critical trial-related procedures and/or to make important trial-related decisions? These are sub-investigators and should be listed on the delegation log (ICH E6 4.1.5).>> Unfortunately it has occasionally become practice to suggest that only physicians can be sub-investigators. This is not true. It is sometimes the case that sites in the USA might be more prone to listing only physicians as sub-investigators, I'm not aware of any statistics on this. In fact the FDA has cited, in Warning Letters, the fact that individuals (such as study nurses, study coordinators, etc) were not listed on the delegation log despite performing important trial related duties. EU inspectors have often made inspection findings because individuals (such as study nurses, etc) performing important trial related duties, were not listed on the delegation log.>> It is often the case that the sub-investigator delegation logs do contain more than just physicians, but I am unaware whether this is changing or not. Perhaps other members of RQA might know if there is a growing trend.>> As you say, many sponsors (& many inspectors) think it is inappropriate to complete 1572 forms for European investigator sites. You should look at the FDA guidance on completing the 1572 - Information Sheet Guidance for Sponsors, Clinical Investigators, and IRBs Frequently Asked Questions – Statement of Investigator (Form FDA 1572) May 2010. -- "The decision to list an individual in Section #6 depends on his/her level of responsibility (i.e., whether he/she is performing significant clinical investigation-related duties). In general, if an individual is directly involved in the performance of procedures required by the protocol, and the collection of data, that person should be listed on the 1572. .... It is not necessary to include in this section a person with only an occasional role in the conduct of the research, e.g., an on-call physician who temporarily dealt with a possible adverse effect or a temporary substitute for any research staff (see ICH E3, Section 6)"
  • Tamara
    20/07/2017 11:52
    Thanks for the answer. Though - considering the answer - I feel that my question might not have been specific enough. It was not a case of not having a study nurse who performs significant trial related activities on the delegation log, but instead not having this nurse documented as sub-investigator. In this example the study nurse was on the delegation log (as study nurse), but not labelled as sub-investigator, while she/he does perform critical trial-related procedures (like taking ICF, discussing AEs, taking vitals, etc). Is this something seen more often? Is this something auditors/inspectors take notice of? As again, according to GCP section 1.56, this person should be labelled as sub-I and thus also be put on the FDA 1572 as such. Right?
  • GCP com
    20/07/2017 14:07
    Original answer stands. Those performing sig tial duties are ich sub-investigators fespite what they might be called. > see fda guidance referenced for details as to who to put on 1572.
  • vasantha reddi
    04/03/2021 20:17
    Hi, regarding the sub investigators, can Residents, who are still not board certified serve as sub investigators in clinical trials? We have a study where we want medical residents adjudicate medical cases and give their diagnosis. 21 CFR 812.3 says that a sponsor shall select investigators qualified by training and experience to investigate a device. So, med residents should be considered qualified by training and experience and therefore can serve as sub investigators in studies right?
  • Anon
    04/03/2021 21:48
    Read ICH E6 R2 1.56 ANY individual member of the clinical trial team designated and supervised by the investigator at a trial site ...
  • Anon
    04/03/2021 22:03
    Depends what they are qualified to do and whether they are legally entitled to perform that task. The PI takes full responsibility for training all sub investigators and supervising their tasks. This supervision must be documented. PI is responsible for subinvesrigators and will be inspected to this. There are many warning letters of findings that PI failed to supervise subs.
  • Dominique Chesnais
    05/03/2021 11:26
    You’ve raised a long-standing query, for which there is no clear and final approach. To the previous comments, I will add that some EU countries refuse to allow investigators at sites to sign the FDA 1572 form (https://www.efpia.eu/media/413440/efpia-cdeg-position-paper-on-the-use-of-form-fda-1572-for-clinical-trials-performed-outside-the-usa.pdf). Spain and Slovenia have been added to the list by their respective Competent Authorities. Second, the definition of sub-investigator is relative to each country. While in the US, a non-medically qualified person (e.g. psychologist) can be a PI, in Europe, only medically-qualified, registered physicians can take patient-related medical decisions as investigators. Also, one should take into account each national regulation about the definition and authorisations of medical personnel, e.g. residents, foreign doctors (EU / non EU), nurse practitioners (UK), etc. Nurses do collect essential trial-related information, but do not make important trial-related decisions. As a corollary, any listed investigators and sub-investigators should also complete financial disclosure forms.
  • Angela McCullagh
    09/03/2021 13:21
    This issue has been driving me bonkers for years. When I started auditing I raised the issue at audit of nurses not being listed as Sub-Invs when conducting significant trial activities (for example completing disease assessments, the scores for which are key endpoints) but was always told that the assignment of Sub-Is is at the discretion of the site's PI and that I can't make it an audit finding. So I'm interested to hear that this has been cited during inspections; maybe I'll start raising it as an issue again...
  • Colin Wilsher
    09/03/2021 14:33
    I take a look. I certainly remember finding about lack of people on delegation log and also (for US only) on 1572. I'll look into it. I always go with the international standard of ICH and audit against that, so if the do trial related activities... etc
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