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Compassionate Use of Investigational Drugs

Arthur L Caplan, PhD Director, Division of Medical Ethics, NYU Langone Medical Center. Amrit Ray MD, MBA, Chief Medical Officer, Janssen Pharmaceutical Companies of Johnson & Johnson.

Q: What is the ethical basis for compassionate use of investigational drugs; and what are some practical considerations in making such use reality?
A: In seeking relief from the burden of disease, some patients face a lack of satisfactory treatment options from the range of available, government regulatory authority approved medicines. In these circumstances, patients often turn to investigational medicines, or “pre­approval access.” The main avenue for pre­approval access is for patients to enter clinical trials. When clinical trials (and related expanded access programs) are already fully enrolled or otherwise unavailable, individual patients – particularly those facing serious and life­ threatening conditions – may seek “compassionate use.”
Clinical trials are geared to deliver the evidence thresholds that allow regulatory approval in order that medicines can become widely available to all patients who need them, or regulatory denial where benefit­ risk is inadequate. In order not to undermine the clinical trials process and its potential to benefit all patients, individual compassionate use grants need to be evaluated using a clear process including pre­defined ethical criteria. The unbridled access to investigational drugs for all individual compassionate use requests could undermine the clinical trials process. An example would be in clinical trials where patients may feel uncomfortable with being randomized to investigational medicine or placebo, when they could instead obtain certain access to investigational medicine through compassionate use requests. An unlimited number of compassionate use grants might thus undermine the benefit to the many that comes from clinical trials supporting the approval of a new medicine. Conversely, when a potentially beneficial therapy is being studied, the absolute denial of all compassionate use requests may overlook the plight of patients in dire circumstances with no other avenue for potential relief. Therefore, a balance is needed to meet both the needs of the many awaiting new approved medicines then or in the future, and the needs of the few who are out of currently available treatment options.
In order to secure fairness, a balanced policy should lay out processes and ethical criteria that will give equitable opportunity to all patients’ requests. Further, the balance should seek to eliminate sources of bias that could result in unfairness based on morally irrelevant criteria such as celebrity or social standing.
We have proposed a mechanism to achieve this balance and are currently conducting a pilot through the use of a Compassionate Use Advisory Committee (CompAC) [The Ethical Challenges of Compassionate Use, Caplan AL, Ray, A. JAMA, 2016; 315(10): 979­-980]. The CompAC insists on anonymizing individual requests to prevent undue influences from wealth, celebrity or other similar factors. We recommend the systematic application of a number of pre­specified ethical criteria, such as do no harm and the requirement to consider current evidence with respect to benefits and risks. Further, we propose that the criteria be evaluated by an independent, objective committee that includes the voices of physicians, ethicists and patients.
The intent of these proposals is to minimize potential bias and allow the equitable consideration of each request for compassionate use. By offering clear information, a transparent request process, including pre­defined ethical criteria and an objective evaluation by those with broad expertise, we believe that the many awaiting new approved medicines and the few seeking compassionate use will each receive a fair chance at the potential benefit from the development of investigational drugs.
COI Disclosure
Caplan serves as the non­voting, unpaid Chairperson of the Compassionate Use Advisory Committee (CompAC), an external, expert panel of internationally recognized medical experts, bioethicists and patient representatives formed by NYU School of Medicine, which advises the Janssen Division of Johnson & Johnson about requests for compassionate use of some of its investigational medicines.
Ray is a full time employee of Janssen Research and Development, LLC.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.