Faculty Bibliography

Patients who suffer from life-threatening illnesses or are stricken with conditions that could result in serious morbidity who have exhausted all appropriate treatments may choose to try, through the Food and Drug Administration's expanded access program, an investigational drug or device in development. The program has succeeded for decades in allowing patients to access potentially helpful but still experimental agents. Nevertheless, the administration of investigational drugs outside of clinical trials raises several ethical issues. Of particular concern are the validity of informed consent and the absence of a framework to ensure that experimental drugs are allocated justly and transparently. Although there are some safeguards to help protect the soundness of consent, little work to date has been done to guarantee that investigational medical products are allocated justly and transparently. We introduce a novel pilot project that seeks to address this issue.

BACKGROUND:The FDA allows patients with a serious or immediately life-threatening illness to use investigational medical products outside of clinical trials through its "expanded access" program. In response to criticism that the process to apply for expanded access is too onerous, numerous changes have been made over the last few years. These have been largely focused on the FDA and the pharmaceutical industry, while institutional review boards (IRBs)-which must approve expanded access protocols, except in emergencies when there is not time to do so-have remained relatively unstudied. We conducted a pilot study to review a sample of publicly available IRB policies from the United States to investigate how these entities handle expanded access. METHODS:We performed an online search to find publicly available policies for IRBs operating in the United States, utilizing a convenience sampling strategy, selecting the first 100 eligible policies we identified. RESULTS:Of the 95 policies reviewed, the majority (92.6%, n = 88) contained language referencing nonemergency expanded access and/or expanded access for emergency requests for a single patient. Of these 88 policies, 11.4% (n = 19) did not explicitly specify detailed procedures for handling nonemergency single-patient expanded access requests. Of the 88 policies that mentioned expanded access in nonemergency situations, 11.5% did not explicitly specify whether full IRB review was required, as was the rule at that time. There was considerable variation in other aspects of these policies, including charging patients for use of investigational products and the use of data from expanded access. CONCLUSIONS:Based on the findings of our pilot, IRB policies on expanded access vary considerably. It is often difficult to find, interpret, and understand IRB policies on expanded access. Further research is needed to determine if and to what extent this negatively impacts patient access to investigational products outside of clinical trials.

BACKGROUND:Janssen Research & Development, LLC, part of the Janssen pharmaceutical companies of Johnson & Johnson, and NYU School of Medicine partnered to establish the Compassionate Use Advisory Committee (CompAC) to evaluate the use of an independent, external, expert committee in ensuring transparent, fair, beneficent, evidence-based, and patient-focused compassionate access to investigational medicines, a public health challenge that has been an ongoing issue for over 3 decades. METHODS:To this end, NYU School of Medicine was responsible for the formation, member selection, and operation of CompAC, consisting of physicians, ethicists, and patient advocates, under Johnson & Johnson's sponsorship. RESULTS:A pilot was successfully run using CompAC to provide recommendations on compassionate use access to a Johnson & Johnson oncology investigational asset called daratumumab. CONCLUSION/CONCLUSIONS:This innovative model provides a framework that can be emulated by the industry globally.

BACKGROUND:Patients who are seriously ill and have run out of available treatment options may seek access to investigational agents that have not yet been fully vetted by regulatory agencies for safety and efficacy and approved for use in human subjects. Over time, a variety of terms have evolved internationally to denote mechanisms for providing access to such unapproved investigational agents. The lack of consistency in terminology used to describe this process is confusing at best and, at worst, possibly even detrimental to patients. METHODS:To highlight variation around the globe in terminology denoting pre-approval access to investigational agents, we conducted extensive Internet searches to locate specific legislation, guidance, or policy documents describing access mechanisms in numerous countries. We created a table of results intended to convey a sampling of international terminological diversity. RESULTS:The profusion of terms used internationally to indicate pre-approval access to investigational agents is evident. We recommend a shift toward the use of "pre-approval access" as an umbrella term encompassing all forms of access to unapproved agents. We also recommend use of the phrases "individual/named patient regulatory routes for pre-approval access" and "group/cohort regulatory routes for pre-approval access" to differentiate between pre-approval access programs designed for single patients, versus those designed for groups of patients. CONCLUSIONS:There is a pressing need to revisit and better align pre-approval access terminology at the international level. Adopting the umbrella term "pre-approval access" may be a useful strategy for initiating and promoting harmonization of terms to reduce potential confusion by patients and health care decision makers regarding experimental treatment options.

As of late November 2016, 32 states had adopted right to try laws. These laws are intended to allow terminally ill patients pre-approval, or "compassionate," access to drugs, devices, or biologics that are in development and have not yet been approved by the United States Food and Drug Administration (FDA). While the laws' intentions and their impact have been examined, little has been written about variations among the state laws. An examination of the specific provisions in and differences among the 32 statutes, and who stands to gain from them, suggests that the benefits of right to try laws are largely rhetorical. So, although the laws have been heralded as pro-patient, they ought to be understood as merely masquerading as patient-centric legislation. We call for a re-examination and amendment or, ideally, repeal of these laws in order to prevent the very real risk of patient harm caused by both some of the laws' provisions and patients' confusion arising from these misleading statutes.

Institutional review boards (IRBs) are one of the bodies charged with prospectively reviewing compassionate use, the hopefully therapeutic use of an unapproved drug in a seriously ill or dying patient who has no other treatment options. However, there are ethical issues in assigning this role to a body whose primary purpose is to review research proposals. The role of IRBs with regard to compassionate use must be examined and potentially revised.