by Julie Fine, BS, legal specialist, Legal Division, Worldwide Research and Development, Pfizer Inc. (Please note: The views presented here are my own and do not reflect the positions or policies of Pfizer Inc.)
On Thursday, I attended Challenges in Securing Coverage for Research-Related Injury, a session which was presented by my colleague, Marc D. Francis, JD, Pfizer Legal, and Karen E. Moe, PhD, University of Washington. Marc began by comparing the challenges in research injury coverage to a plot device used in the movie Vantage Point, in which a single event (an attempted presidential assassination) is portrayed from the perspective of multiple witnesses. Recollections of the event varied greatly depending on each individual’s point of view and proximity to the action. Marc likened the different perspectives to the views and biases of pharmaceutical sponsors, academic institutions, and, most importantly, the subjects who consent to participate in research injury coverage studies.
By definition, subject injury is an adverse clinical event experienced by a subject as the direct result of participation in a clinical trial. Subject injury language in clinical trial agreements allocates responsibility for coverage of injuries incurred by subjects outside of common law tort actions. It does not cover pre-existing conditions, natural disease progression, injuries from regularly scheduled care, or negligence of physician or clinical staff.
Currently, U.S. law does not require sponsors to cover medical expenses for subject injuries or to carry liability or other insurance. According to the Common Rule (42 CFR § 46.116(a)(6)) and Food and Drug Administration (FDA) human subjects protection requirements (21 CFR § 50.25(a)(6)), informed consent must include details on whether compensation or medical treatment is available if injury occurs, but compensation and/or medical treatment is not required.
Alternatively, guidance from some internationally respected sources instructs research injury practices somewhat more specifically. For example, ICH E6 Good Clinical Practice states that the “investigator/clinical site should ensure that adequate medical care is provided to a subject for any adverse events during and after participation in clinical trial (Section 4.3.2) and sponsor policies should address the costs of treatment of subjects in the event of subject injuries in accordance with applicable regulatory requirements (Section 5.8.2).” The Association for the Accreditation of Human Research Protection Programs (AAHRPP) also requires a written agreement with the sponsor that addresses medical care for research participants with a research-related injury, when appropriate (Domain I (Organization) and Element I.8.A). Additionally, the American Medical Association Ethical Opinion E08.0315 includes a provision that “physicians-researchers must ensure that protocols include provisions for funding subject medical care in the event of complications.”
From an international perspective, the United Kingdom, South Africa, Australia, New Zealand, and Singapore have all adopted compensation systems modeled on the Association of the British Pharmaceutical Industry (ABPI) guidelines. Brazil has adopted a holistic approach where compensable injuries include the “possibility of injury to the physical, psychic, moral, intellectual, social, cultural, or spiritual dimensions of the human subject.” In response to recent controversy, the Indian Council of Medical Research has drafted very broad guidelines which include regulations involving failure of an investigational product to provide intended therapeutic effect, administration of placebo providing no therapeutic benefits, and adverse effects due to concomitant medications.
From a best practices perspective, clinical trial agreements and informed consent documents ought to address subject injury provisions as well as what will happen if a subject is injured relative to the research. Two exemplary templates are:
- The proposed Institute of Medicine template
- The National Cancer Institute/CEO Roundtable Harmonized Clauses template
Marc also recommended:
- The Association of American Medical Colleges (AAMC) brochure: Clinical Trial Contracts: A Discussion of Four Selected Provisions
- Recovering From Research: A No Fault Proposal to Compensate Injured Research Participants by Elizabeth R. Pike
- Compensation For Injured Study Subjects In Clinical Trials: An Ethical Obligation In Human Subjects Research by Bianca Buechner
Karen Moe described University of Washington’s compensation program—Human Subjects Assistance Program (HSAP)—which has been in place for 30 years. HSAP is a no-fault program “developed to provide medical and other assistance to subjects who experience a research-related medical problem that is likely caused by University-conducted research.” The program does not apply to industry-funded-and-initiated-research or to non-healthy volunteers in Phase 0-1 studies, and is limited to $10,000 for out of pocket expenses and to $250,000 write-off of care provided in a University of Washington hospital. None of this compensation comes from indirect fees. The HSAP program is not without some challenges, among them being:
- Medicare Secondary payer rule (won’t pay if there is a promise another source will)
- Complex billing scenarios (who pays and how it is administered)
- Consistency (between contract terms, budget, and consent document)
- MMSEA (avoidance of dual payment)
- Research Burden (administering two and three)
Karen referenced the excellent presentation by Kenneth Feinberg at a meeting of the Presidential Commission on the Study of Bioethical Issues about research injury compensation.
I hope I have time to read some of these materials! And I’ll have to rent Vantage Point on Netflix when I get home.