In May 2015, Johnson & Johnson (J&J) and the Division of Medical Ethics at New York University Grossman School of Medicine (DME) embarked on a novel pilot program to support equitable expanded-access allocation of a J&J investigational medicine. Expanded access (EA), also known as compassionate use, is a treatment pathway, regulated by health authorities, to allow access to investigational medicines outside of clinical trials for seriously or terminally ill patients who have exhausted approved treatment options and are ineligible for a clinical trial. Treating physicians may request this access on behalf of their patient(s) from the company developing the medicine.
Concurrent to the nascent collaboration, patient and caregiver communities were publicly expressing frustration with companies they felt had overlooked or failed to provide responses to requests for investigational medicines. The case of Josh Hardy, in particular, highlighted issues surrounding EA and the unclear processes some companies employed for handling such requests, igniting passionate media discussions. These discussions spurred intense pressure on the company developing the drug that Hardy’s physician was requesting, which in turn spurred interest from the bioethics community.
The J&J investigational drug under consideration was in the final stages of clinical trials, with a limited supply of the drug available for EA use. It had shown considerable promise in trials, and high demand was expected from physicians with patients with unmet medical needs who were ineligible for a trial. In recognition of the public dialogue, and in parallel to codifying their EA policy, J&J sought guidance from the DME on responding equitably and consistently to individual patient requests without jeopardizing the clinical trials essential for submission of data to health authorities.
The head of the DME (Caplan) had extensive related experience in the ethics of organ allocation for transplantation, including building criteria and a regulatory framework to guide decisions about which patients would receive organs in short supply. He had also consulted with the company CEO involved in the Hardy case. Thus, there was a natural synergy in a potential collaboration to develop a model to ethically allocate an investigational medicine for J&J. The objective for the company was twofold. One, to protect the integrity of the clinical development program for the drug, the primary and preferred route for accessing investigational medicines, and two, to create a systematic, fair process for evaluating inevitable requests when the supply of the drug is limited.
The result was the Compassionate Use Advisory Committee (CompAC), a first-of-its kind alliance between industry and academia dedicated to developing an ethical framework for allocating a drug via the EA pathway The alliance was widely covered in the press when it was announced in the spring of 2015, and met with mixed reactions from both industry and academia. Some heralded it as a pioneering mechanism to ensure equitable allocation of a limited drug, while others questioned the motives of both parties. Some wondered whether the responsibility of the company to allocate their products under scarcity was being handed off for reasons of liability or optics, while still others, from the academic side, were skeptical about even the idea of an alliance between industry and academic ethics, fearing the DME might be endorsing, inadvertently or otherwise, a pharmaceutical product for profit.
For the 10-year anniversary of the pilot project, we review the success of CompAC and how it has evolved from a pilot program. The CompAC model remains an important patient oriented, industry–academic ethics collaboration a decade later, growing from one independent panel, reviewing requests for one scarce investigational drug for one disease, to a long-term collaboration between a major pharmaceutical company and an academic medical center’s bioethics program with several therapeutic area–specific CompACs whose scope now extends beyond advising on single patient EA requests.
CompAC remains co-chaired by DME faculty and still comprises international physicians, ethicists, and patient representatives to review single-patient requests and make recommendations to J&J regarding requests for their investigational medicines. In the pilot phase, CompAC reviewed each single patient request and provided recommendations to J&J on how to prioritize patients to receive the limited supply, according to the ethical framework developed by CompAC. Now, J&J, with advice from CompAC, internalizes reviews, requesting review assistance only for unusual or novel requests.
Importantly, the Division of Medical Ethics, as an academic entity, regarded the collaboration as a research effort, and J&J agreed. DME and CompAC members were therefore able to publish on the process and share the model. Details about assembling the committee, deliberations behind the resulting framework, and how the CompAC reviewed requests have been previously written about.
Following the pilot period, an external firm assessed the model and concluded that J&J and the DME had achieved their go.l of equitably assessing requests. Subsequently, J&J expanded this model to their investigational pipeline, and therapeutic-specific CompAC groups were assembled by the DME. J&J also incorporated a required CompAC review into their drug-specific EA strategy development to allow a fulsome assessment of not only single patient requests but the criteria for managing each new investigational medicine, as well as which, if any, cases would require CompAC review. This was beneficial to all parties: it allowed CompAC to have deeper insights that helped inform its recommendations, and J&J teams were beneficiaries of CompAC’s bioethical lens on their EA/compassionate use plans.
This comprehensive bioethics and evidence-based framework continues to help Johnson & Johnson today by minimizing inherent biases—biases that could otherwise prevent the company from recognizing what is considered equitable by CompAC. Having this framework has strengthened the company’s collective framework of transparency, consistency, and equity for each of its expanded access programs.
The CompAC framework and processes have been replicated in both industry and nonprofit sectors, far beyond J&J. For example, in 2017, the nonprofit ge2pe2 Global Foundation was formed to provide bioethics advice on various areas to pharma and biotech. Its preapproval access consultation process was directly adapted from the J&J and DME collaboration.
The success of the CompAC model depended not only on human and fiscal resources but also on a sustained commitment to asking questions of the framework when required and the ability to adapt to shifts in therapeutic demand. Importantly, it required industry leaders who were willing to ask for and withstand ethics scrutiny of their policies and practices, as well as share best practices learned during the collaboration through publications and presentations. CompAC has demonstrated that the process of requesting access to investigational medicines could be enhanced through a collaborative alliance between academia and industry that jointly prioritized equity and consistency to support patients with unmet medical needs.
The alliance operated under the belief that creating and implementing a transparent framework for decision making was both feasible and could reinforce the integrity of this important treatment option for physicians and their patients, as well as for the public understanding of EA. Ultimately, it has demonstrated that just decision-making is not only feasible, but more importantly, sustainable.
Christine MacCracken, MSHEd, BSN, is the executive director, Patient Strategies and Solutions, Office of the Chief Medical Officer, Johnson & Johnson Innovative Solutions.
Lisa Kearns, MS, MA, is the senior research associate in the Division of Medical Ethics, NYU Grossman School of Medicine.
Arthur Caplan, PhD, is the founding director of the Division of Medical Ethics, NYU Grossman School of Medicine.