J&J Leads the Way in Developing a Rational Process for Responding to Compassionate Use Requests

Filed in Clinical Research, Drugs & Devices by on May 15, 2015 0 Comments

By Carl H. Coleman

Global pharmaceutical giant Johnson & Johnson announced last week that it had appointed Arthur Caplan, a prominent bioethicist, to establish a Compassionate-Use Advisory Committee (CompAC) to make decisions about patients’ requests for access to unapproved medications outside of clinical trials.  The decision is a welcome development that other companies would be well advised to follow.

Background

The federal Food, Drug, and Cosmetic Act prohibits companies from distributing drugs in interstate commerce until they have received FDA approval for at least one indication.  The main exception to this prohibition is the “investigational new drug,” or IND, process, which allows manufacturers to distribute unapproved drugs to participants in clinical trials.  Without this exception, companies would be unable to develop the safety and efficacy data needed to apply for FDA approval.

For a variety of reasons, however, some patients who might benefit from unapproved drugs are unable to enroll in clinical trials.  Some patients may live too far away from the trial site to make participation realistic.  Others may not meet all of the study’s inclusion and exclusion criteria; for example, they may be too old or too young, or they may have comorbidities that disqualify them from participation.

For these patients, the FDA offers alternative mechanisms for obtaining access to unapproved medications.  These mechanisms are collectively referred to as “expanded access” or, more informally, “compassionate use.”  To qualify for expanded access, the FDA must determine that the patient has a “serious or immediately life-threatening disease or condition” for which “no comparable or satisfactory alternative therapy” exists; that the potential benefits of the unapproved drug justify the risk, and that “those potential risks are not unreasonable in the context of the disease or condition to be treated;” and that providing the unapproved drug “will not interfere with the initiation, conduct, or completion” of the clinical trials needed to obtain marketing approval.  If the FDA determines that all of these conditions have been satisfied, the company is permitted – but not required – to provide the drug to patients outside of clinical trials.

Efforts to Broaden Expanded Access

In the 2006 case of Abigail Alliance v. Von Eschenbach, an organization formed by the father of a young woman who was dying of cancer claimed that the FDA’s expanded access program infringed on the constitutional rights of patients who are terminally ill.  Specifically, the organization claimed that terminally ill patients have a constitutionally protected right to obtain any potentially life-saving medication that has passed Phase I testing, without first having to obtain the FDA’s acquiescence.  A three-judge panel of the D.C. Circuit ruled in favor of the organization, but that decision was later overturned en banc.  As a result, the FDA’s expanded access program remains the only way to obtain access to unapproved medications outside of clinical trials, even for patients who are terminally ill.

Over the past year, over a dozen states have sought to expand terminally ill patients’ ability to obtain unapproved medications by enacting so-called “right to try” laws.   These laws purport to authorize manufactures to distribute unapproved medications to terminally ill patients without having to comply with the FDA’s expanded access requirements.  For example, Michigan’s right to try law states simply that “a manufacturer of an investigational drug, biological product, or device may make available and an eligible patient may request the manufacturer’s investigational drug, biological product, or device,” without ever mentioning the need for obtaining FDA authorization. Indeed, advocates of these laws have made clear that their goal is to completely remove the FDA from the decision-making process.

While these laws may make great “political theatre,” as both practical and legal matters they are basically irrelevant. They are practically irrelevant because the FDA almost never denies an expanded access request; according to a senior FDA official, the FDA has granted over 99 percent of requests for expanded access since 2009. While some critics have complained that the FDA’s expanded access rules are too cumbersome, the FDA has recently proposed changes to the process that are expected to reduce the time for completing an application from 8 hours to only 45 minutes.

The laws are also legally irrelevant because, in the rare case that the FDA does deny a request (or in situations where a patient seeks to obtain expanded access without first requesting FDA authorization), a manufacturer who complied with the request would be in violation of the federal prohibition on shipping unapproved drugs in interstate commerce. Under basic principles of federalism, a state law cannot authorize conduct that federal law explicitly forbids.

Johnson & Johnson’s Contribution

In contrast to these largely symbolic state laws, Johnson & Johnson’s new initiative recognizes that the real issues with expanded access are not at the level of the FDA but within the pharmaceutical companies themselves, as it is the companies that ultimately decide whether to grant patients’ requests. Manufacturers have “significant reasons that might lead them not to provide compassionate-use access.” For example, the FDA has stated that, although data generated through expanded access programs may be used to establish problems with a drug’s safety profile, “it is very unlikely that … expanded access … would yield effectiveness information that would be useful to FDA.” In other words, it is far more likely that expanded access will generate information that detracts from, rather than strengthens, the company’s ultimate approval application. Moreover, the FDA does not permit companies to earn a profit on drugs provided through expanded access programs. While companies are permitted to recover their actual costs, many companies choose not to charge patients for the costs of expanded access drugs because they do not want the public to know that the true cost of the drug is far less than the price that will ultimately be charged if the drug gains approval. (Of course, this concern may become moot if pending state-law proposals to require manufacturers to disclose the development costs of certain drugs are eventually adopted.)   Companies may also have legitimate concerns about the impact of large expanded access programs on the ability to complete clinical trials in a reasonable time frame, particularly if supplies of the drug are limited.

Critics of Johnson & Johnson’s move claim that, by outsourcing decisions about compassionate use to an independent panel, the company is simply “passing the buck on tough decision-making.” In fact, far from “passing the buck,” the company’s actions show that it recognizes that complex assessments of ethical issues require a systematized, deliberate, and accountable process.  The need for such a process is particularly pronounced given the increasing use of social media campaigns to “shame” companies into granting specific patients’ expanded access requests.  Companies that make expanded access decisions on an ad hoc basis, with no effort to develop overarching standards or to ensure that the those standards are applied consistently, are more likely to be swayed by emotional appeals on behalf of well-organized patients, as opposed to objective considerations applied to all patients equally.

The ultimate effectiveness of the new panel will depend in large part on how it is structured and operated.  As scholars have observed in a variety of contexts, ethical judgments about the appropriateness of engaging in risky activities depend in large part on the background and personal characteristics of the individuals making the decisions.  It will therefore be important to ensure that the panel’s membership includes individuals from diverse professional and personal backgrounds.  The quality and consistency of the panel’s decisions could also be enhanced by incorporating formal mechanisms for systematizing the decision-making process, such as the use of “decision banks” to facilitate comparisons of different situations raising similar issues.

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