Last week some-one asked me what it is that industry can and can not do in investigator initiated trials (IITs). The challenge in answering this question goes back to the question who the sponsor – and therefore the one being responsible – for the concerning study is. Not just who initiated the clinical study.
Clinical Study Sponsorship
A presentation addressing IITs and clinical sponsorship you can download here, but sponsorship within the context of a clinical study is well and unanimously defined by ISO 14155 and ICH GCP. The ISO definition of sponsor:
“Individual or organization taking responsibility and liability for the initiation or implementation of a clinical investigation.”
The ICH GCP definition of a Sponsor-Investigator:
“An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.”
This definition differs from the typical commercial definition of sponsorship and this can lead to confusion. Key is that sponsorship comes with liability, and it is therefore essential that roles and responsibilities are clearly defined and documented.
Industry Clinical Study Support
What may further confuse the situation is that sometimes industry supports the clinical study managed by the investigator through provision of for example products or funds. In such cases, the following are the 4 key things to do:
- Document who initiated and is the sponsor of the concerning clinical trial,
- Ensure that all clinical study documents are in line with the concerning agreement,
- Ensure that the sponsor-investigator has access to all required study product safety information, and
- Ensure that every-one, including sales and the investigator-sponsor, is aware of their roles and responsibilities and does not deploy any activities outside of what is agreed to.
Especially the latter is where things may easily go wrong as people unintentionally deploy sponsor activities outside of the agreement, thereby giving a wrong impression to those not directly involved.
Addressing all tasks and responsibilities of an investigator-sponsor goes beyond the scope of this blog, but in essence it is a combination of those of a sponsor and an investigator. A more extensive overview and with a focus on investigator-sponsored clinical trials with FDA regulated products can be found here, but in brief they include:
- Develop and ensure compliance with the study protocol
- Selection and monitoring of investigation site(s)
- Ensure regulatory approvals are obtained per local regulation
- Ensure proper Subject Information and Informed consent process
- Develop Case Report Forms and data collection and cleaning tools
- Adverse Event collection and reporting to EC(s), Health Authority(ies), and possible other investigators
- Data analysis and reporting
Keeping in mind that this list is just a snap shot, one can easily see that the sponsor tasks and responsibilities concern a substantial amount of work. An investigator-sponsor may well underestimate this, especially when it concerns a multicenter study, and when industry chooses to support an IIT, it becomes key to monitor study progress closely and provide additional support when the ethical and scientific integrity of the trial is at stake.
As of note in this respect is that the European Medical Device Regulation in preparation is very likely to include sponsor’s obligations and to require that clinical trials with medical devices are in line with ISO 14155 and the Declaration of Helsinki. In other words, moving forward the requirements in this respect will become uniform across Europe and it is even more important to ensure clarity with respect to roles and responsibilities also when it concerns a single center physician sponsored study.
Reading the above one may wonder why industry would even go though the effort of supporting an IIT? To my idea there are plenty of reasons to do so, but probably the most important one is that such a clinical study typically reflects the physician/ clinician’s perspective. These trials tend to be much more driven by daily practise than industry-sponsored clinical studies under a strict protocol and therefore should to be seen as complementary in the complete clinical evidence package.
In short, the answer to the question is relatively straightforward: In my opinion industry can do anything in relation to an IIT as long as roles and responsibilities are clear and complied with by all those involved. Close monitoring, however, is warranted, otherwise this type of activity can become like a heath fire: unpredictable and sometimes unintentionally causing harm.
Please feel free to contact me in case of any questions or interested in a more in depth discussion regarding the above.