My open letter to the FDA and the Regan-Udall Foundation about their proposed compassionate use navigator

Navigating what, why?

Navigators are the solution de jour. The question they raise is, what problem are they solving?

The Reagan-Udall Foundation (RUF) for the U.S. Food and Drug Administration (FDA) is proposing the creation of a navigator to provide information on the process for requesting individual patient access to an investigational drug outside of clinical trial, something commonly known as “compassionate use.”

According to RUF, the proposed navigator would likely consist of a website and potentially a call center to assist patients and healthcare providers who require more personalized assistance. Its goal would be “to increase transparency and accessibility of information, and thereby increase understanding of” compassionate use, in order “to help guide patients and clinicians through the request process.”

This is a laudable goal. It is difficult for those interested in requesting single patient access to investigational medicines to know who to contact, how, or what information will be requested of them. Indeed, those who are confused and seeking guidance frequently call the FDA. The FDA is to be credited for taking this issue to the RUF and for seeking guidance about how to best serve individuals with questions or requests.

But let us be clear about what requesters want. They are seeking information about how to request access to investigational drugs not from idle curiosity but because they wish to obtain these drugs for use. Such requests occur when patients have no approved therapies available to them and are unable to participate in a clinical trial. Such requests are normally time-sensitive and, because a patient’s life is at stake, are highly and understandably emotional. Thus, while a navigator that offers information will be useful to requestors, it will fall short of providing them what they really want, which is access to a drug.

So, if requestors really want access to investigational drugs, is there anything that the FDA can do to provide this? In short, no. Companies own their investigational products and it is up to them to decide who gets access. However, there are certainly things the FDA could do to remove disincentives from the path of companies that may be willing to provide patients compassionate use access to investigational drugs.

First, the FDA needs to write and publish a statement assuring companies that the agency understands serious adverse events (SAEs) can and will happen in compassionate use settings and that such events will not constitute a “kiss of death” in the eyes of the regulator. The FDA has stated this multiple times, and it is in line with the fact that the FDA does not routinely halt drug trials when patient deaths occur outside of trials. What is needed is for the FDA to put this statement in writing. More importantly, the FDA needs to conduct an audit, either retrospective or prospective, of what percentage of new drugs are approved despite deaths or other SAEs in non-trial use of the drugs. Such an investigation and report would go far toward helping companies feel reassured that compassionate use, even among the very sick, will not result in the derailment of their costly and lengthy drug development process. Such an audit will not be easy, but its value would justify the complexity of the task.

Ought some SAEs in the compassionate use setting result in trials being halted? Yes, and the FDA and the company have the necessary expertise to work together in these cases to figure out what went wrong and what, if anything, can be done to prevent such outcomes in future patients. But not every SAEs merits such a review. The FDA reportedly has investigated how many times it has imposed a “clinical hold” on drug trials due to a SAE in the compassionate use setting, and the number is minimal. This report ought be published and, if it is not comprehensive, its purview ought be widened to cover all parts of the agency. Again, companies desire evidence that bad outcomes will not unnecessary jeopardize their drug development activities (and, of course, their financial and organizational wellbeing).

If companies understand that the FDA will not automatically penalize them for SAEs in the compassionate use setting but will rather use discretion in deciding which SAEs to investigate, will all companies open their doors to those seeking access to their investigational drugs? No. But this one factor is more likely to expand patient access than building a navigator or any other proposal currently on the table.

So where does this leave the proposed navigator? The navigator, if designed purposefully, implemented well, and supported over time, would be helpful with regard to a secondary concern of those seeking access — the idea that people who know how to work the system can get access that eludes others. A navigator could be helpful in making sure requestors are able to contact companies with their requests and in channeling these requests to a central point within each company. The day should long be over when those who have a brother-in-law working at the company or who have access to their state senator can get their requests considered while those calling the company’s 1–800 phone number end up in phone tree oblivion. To the extent that a navigator can direct those seeking to make contact with the company to the correct website, phone number, or person, this is a good thing, increasing fairness and decreasing frustration. There is no reason, however, that such an operation need be operated by either the FDA or the Regan-Udall Foundation. Indeed, the pharmaceutical industry may be the best suited to run such an informational clearing house, either by itself or in concert with a broad-based patient advocacy organization that specializes in patient education.

Is there any reason that a navigator ought not be run by the FDA or the RUF? The FDA budget is a perennial issue, and any money spent running the navigator ought not be taken from the agency’s already insufficient budget. The same should be said for the agency’s understaffed human resources — if a new navigator service is created, let it rely upon new hires, not be added to the job description of already busy staff. But the main argument against having a navigator, especially one built around a webpage, run out of the FDA or the RUF is logistical. We do not want a webpage that has thousands of links to company webpages that will go inactive and need to be maintained. We do not want a webpage with lists of phone numbers that go out of service when small companies are acquired by larger ones. We do not want a webpage that promises assistance only to result in frustration. We already have one of these, and it is called ClinicalTrials.gov.

The way to help minimize anger and frustration on the part of those seeking access to investigational drugs is multi-pronged. First, modify ClinicalTrials.gov so it provides a user-friendly way for doctors and patients to navigate up-to-date information. Second, by all means, create a navigator to help patients and/or physicians with individual requests for investigational drugs — but do so with the appropriate resources and design to ensure the navigator does not to end up in the dust heap of patient-friendly ideas that did not work as intended. And finally, understand that no matter what assistance is provided to those seeking to make requests, some requests will be denied. There are steps the FDA can take to make companies less reluctant to grant such requests, and these ought be seriously investigated. Even so, there will always be some requests that do not result in access to the desired product. For these denials to be perceived as acceptable — albeit anguishing — it is in the companies’, and the pharmaceutical industry’s, best interests to devise access policies and procedures that are transparent and fair and to make them public, with or without a navigator to assist in this process.

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