Dr. Jonathan J. Darrow, an expert on FDA policy and faculty member at Harvard Medical School, spoke with Bill of Health editor Alex Pearlman this week about the new so-called “Right to Try” law, how it is different from existing regulations, and why expanded access programs will never work without thinking about resources differently.
Alex Pearlman: Expanded access isn’t new. So why do we need Right to Try?
Dr. Jonathan J. Darrow: We probably don’t. Despite its name, the new Right to Try law may be unlikely to improve patient access to experimental treatments. Under the expanded access program as it existed before the recent law was enacted, the FDA granted almost all of the requests that it received.
But that doesn’t mean that almost all patients who wanted expanded access got it. The reason is that there are several participants in this process that need to give their consent for the patient to obtain the drug. The patient, of course, must give his or her consent. But the patient must also find a doctor who is willing to prescribe a drug for which there is little evidence available. And because the risks are higher and the benefits are less certain for experimental drugs, physicians who want to make sure their patients are not harmed may be understandably hesitant to prescribe these drugs. In addition, some physicians may not have been aware of the FDA’s previous expanded access program. Or, they may have been aware of the program, but unfamiliar with the process and concerned about the amount time needed to complete the paperwork, given the many competing demands on their time.
But the most difficult barrier to overcome is not FDA, or physician-unwillingness. In most cases, it is the drug manufacturer. A drug manufacturer—particularly those that are early-stage companies—may not have enough of the drug on hand to be able to provide it to patients outside of clinical trials. Even if a drug company very much wants to provide a drug to help as many patients as possible, it may simply not have the product available to provide. There is also substantial paperwork for the company…which is not mere red tape but which is needed to help keep the FDA informed of usage and outcomes. In addition, companies may be concerned that adverse effects resulting from expanded access could slow approval or lead to negative media attention.
So there are a lot of reasons why a company might not want to give out an experimental drug before FDA approval. And most of those reasons don’t change very much or at all under this new law.
AP: So, why has there been so much public demand for a Right to Try law?
JD: The basic rationale behind expanded access is that patients with serious or life-threatening illnesses may be willing to take greater medical risks. It is understandable that patients feel they should be able to make their own evaluation of the risks and benefits [of a treatment] and try whatever is available that might help, without interference from the government.
One of the provisions in the law is that the patient has to give his or her informed consent. But informed consent means providing the patient with adequate information—sufficient information to make an informed decision. And the problem with access to unapproved drugs is that the information often just isn’t available. There is lots of promise, but little reliable information.
If you are not someone who studies drug data for a living, it can be easy to look at information that looks promising early on [in a drug’s development cycle] and interpret that information as suggesting a higher probability of benefit than the drug will actually turn out to offer. It is important for patients to remember that most experimental drugs look very promising early in development (if they didn’t, drug companies wouldn’t pursue them), but that most nevertheless fail at some point before approval, either because they have no efficacy at all, or because they actually turn out to cause more harm than good – which could potentially cause a seriously ill patient to experience even greater suffering, or an even more shortened lifespan, or both.
AP: So, this is a scientific problem, not a problem of over-regulation?
JD: Exactly. There is no question that there are patients who have serious unmet medical needs. This was the case before 1987 when the FDA’s expanded access program was first formalized. And it remains the case today after the enactment of the Right to Try law. The law, unfortunately, can’t change that. The new legislation reflects the desire—of everyone—to do something to help patients. There is tremendous desire on the part of patients, scientists, legislators, and FDA personnel. But the problem is not the legislation. The problem is the lack of drugs that actually resolve patients’ health problems.
AP: What can we do to help these patients, if the answer isn’t a legislative one?
JD: We need to shift our allocation of healthcare dollars, and do a better job of creating the drugs or other interventions that patients need.
In my other work on Breakthrough drugs (here and here and here), and on the minimal drug efficacy standard (here and here and here), we have demonstrated that there are drugs being approved, promoted, and utilized that offer very small benefits. At the same time, these drugs may be very expensive. So all the money that is used to develop, review, manufacture, and promote these drugs would be much better spent on early stage research.
This issue of resource allocation needs more attention.