- Consider why your company supports (or wants to support) investigator-initiated research. There are several reasons why your company may want to support investigator-initiated research. The research could provide important benefits to your company in the form of new ideas and valuable clinical data. The research also may advance medical and scientific knowledge of a disease state or an otherwise under-studied patient population. Your company should understand these reasons because they will help the company to define its priorities for investigator-initiated research projects.
- Remember that the parties involved in the research have mutual goals. Although industry may support investigator-initiated research for a variety of reasons, all parties involved — investigators, clinical sites, and your company — should establish several mutual goals for the research. These goals should include generating quality research that results in publications and high quality data, good partnerships and continuing relationships, and, of course, protecting human subjects and ensuring regulatory compliance. Investigator-initiated research can often complement a company’s R&D goals, and in some specialties, a substantial portion of innovation may result from investigator-initiated research projects. As with your company’s reasons for supporting the research, these goals should underpin how the research should be structured and conducted.
- Establish pre-defined criteria for the review and approval of the research. An important part of standardizing company review of and support for investigator-initiated research is defining in advance the types of research a company will support. For example, research may focus on a therapeutic area, disease state, patient population, or other factors. Your company should require written proposals from investigators demonstrating that the proposed research fits within the company’s established criteria.
- Have a pre-determined, multi-disciplinary group review the proposal. Instead of allowing varying personnel to review proposed research on an ad hocbasis, your company should ensure that research proposals are funneled into a common repository. For example, many companies are implementing an integrated on-line submission system; research proposals that are submitted on an informal basis must be re-routed through the established system. The research proposals are then reviewed by a standing internal committee. Most often, this committee will be comprised of medical/R&D personnel. Your company should not let sales and marketing personnel influence the committee’s operations.
- Establish your company’s role in and oversight of the research. Your company should think about the role it wants to have in investigator-initiated research. For example, does the company want to comment on the protocol? Require the investigator to submit certain research reports or report adverse events to the company? License the research data? Be able to audit or monitor the research? Review research publications? Train the investigator and others? Although your company’s level of participation may vary by the particular research project, the company should think about what level of participation and oversight it wants to have. At the same time, these activities must be balanced with the limitations on regulated industry’s interactions with health care professionals and with preserving the investigator’s regulatory status as sponsor.
- Have a written agreement. Quite simply, your company should enter into a written agreement for investigator-initiated research before the research begins. This agreement serves several important purposes, including: (i) establishing the elements of the company’s participation — such as protocol review/comment, research-reporting obligations, ownership of research data, company auditing and monitoring rights; (ii) setting forth provisions to protect the company, the investigator, and the research site in case something goes wrong; and (iii) helping to ensure the confidentiality of information a company may provide to an investigator. The agreement also memorializes the key distinction between investigator-initiated research and sponsored research: in investigator-initiated research, the investigator is the regulatory sponsor of the research and must comply with all associated regulatory obligations.
- Remember the written agreement is different from other clinical research agreements. Your company should be aware that as a general rule, the provisions of an agreement for investigator-initiated research tend to differ from the provisions of industry-sponsored research agreements. For example, investigators often will own the data in investigator-initiated research, whereas in industry-sponsored research, the industry sponsor nearly always requires data ownership. On the other hand, provisions like indemnification and study-subject injury may be more limited in an investigator-initiated research agreement than a traditional sponsored research agreement. There may be several other differences between an investigator-initiated agreement and an industry-sponsored agreement, because the circumstances of the research projects can vary widely.
- Appreciate the increasing FDA scrutiny of clinical trials, and on the specific risks involving industry support of investigator-initiated research. In recent years, multiple federal agencies have increased their scrutiny of clinical trials. In particular, the U.S. Food and Drug Administration (FDA) has ramped up its Human Subject Protection/Bioresearch Monitoring (HSP/BIMO) Initiative, issued numerous new regulations and guidance documents, improved its internal procedures and communications, implemented a more efficient debarment and disqualification process for investigators, and entered into a partnership with the European Medicines Agency (EMEA) to inspect and evaluate clinical research spanning multiple global jurisdictions. The company should have a framework for supporting investigator-initiated research and maintaining compliance with these regulatory considerations. Suggestions for structuring such a framework are provided below.
- Understand and appreciate the application of fraud and abuse laws to clinical research. In addition to the FDA’s focus, your company should be aware that the HHS Office of Inspector General (OIG) has issued compliance guidance for manufacturers that addresses investigator-initiated research. That guidance explains the government’s concern that a manufacturer’s funding of research conducted by customers can be used to induce or reward the purchase of the manufacturer’s products. The guidance includes several recommendations to manufacturers that are intended to deter improper conduct or the inference of improper conduct under fraud and abuse laws. In addition, private trade organizations including the Advanced Medical Technology Association (AdvaMed) and the Pharmaceutical Research and Manufacturers of America (PhRMA) have issued important compliance guidelines that address investigator-initiated research. As with the FDA considerations described above, your company’s investigator-initiated research support program should be structured with these criteria in mind.
- Implement procedures to standardize your company’s support of investigator-initiated research. An informal survey conducted by pharmaceutical business intelligence firm Cutting Edge Information indicated that one-third of pharmaceutical and biotechnology companies did not have an established process for tracking investigator-initiated research. In the current enforcement environment, this approach is risky. A manufacturer’s compliance policies and procedures should include a standard mechanism for tracking review and support of investigator-initiated research. Examples of issues addressed by these policies and procedures are provided below.
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