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As the winds of change blow away the lingering odors of the “right to try” miasma, it’s time to get serious about expanded access 2.0.

Last week, more than 500 people from industry, academia, government, and patient advocacy groups convened at the National Press Club in Washington to discuss, debate, and develop what comes next for expanded access, also known as compassionate use. The first voice to be heard was Dr. Janet Woodcock, director of the Food and Drug Administration’s Center for Drug Evaluation and Research, in a “fireside chat” I had the honor to moderate. Woodcock shared her belief that expanded access programs are only an iterative step towards more regular and robust use of platform trials.


Platform trials, which involve simultaneously studying multiple therapies for a single disease, provide an innovative pathway for broader access to experimental rare disease treatments. Platform trials can target a variety of subtypes of a disease and enroll “just about anybody who is willing to enter the trial,” Woodcock noted. Her hope is that drug developers will someday be more willing to pursue master protocols (clinical trials intended to simultaneously evaluate more than one investigational drug or more than one cancer type in an overall trial structure) if there were more successful examples of them. Step right up, ladies and gentlemen of the drug development industry.

But the issue of expanded access also exists in the present tense, and many thorny issues persist. One of the most significant issues is the silent elephant in the room: Who should pay for access to experimental medicines, and how much should they pay? Right to try doesn’t mean right to try for free.

Current FDA guidance offers only the ability to recover direct costs such as how much it costs per unit to manufacture the drug — raw materials, labor, and nonreusable supplies and equipment needed to make the quantity of drug required for the patient’s use — or costs to acquire the drug from another manufacturing source plus shipping and handling. In short, drugs offered under an expanded access protocol cannot be priced for profit.


In the wake of the imbroglio over BrainStorm Cell Therapeutics’ considering embracing a right-to-try strategy for expanded access to its experimental ALS compound that included charging a “semi-commercial” price significantly higher than its direct costs, the debate over expanded access reimbursement has come front and center. Insurance doesn’t generally cover treatments that haven’t been approved by regulators. But should it?

In a 1991 memo, Bill Gates said this about the company he co-founded: “Microsoft is not about greed. It’s about innovation and fairness.” How can we apply this philosophy to the economics of expanded access?

Here’s one way to think about that. In his now-classic book, “The Wealth of Nations,” Adam Smith wrote, “It is not from the benevolence of the butcher, the brewer, or the baker that we expect our dinner, but from their regard to their own self-interest.” If we replace those three worthy 18th-century tradesmen with the 21st-century drug developer, payer, and patient, what might the “The Wealth of Expanded Access” look like?

The self-interest of the developer regarding expanded access includes an opportunity for even earlier conversations with formulary committees, an opportunity to recover some development costs, the satisfaction of doing the right thing, and the ability to capture valuable data. Dr. Robert Temple, the deputy center director for clinical science at the FDA’s Center for Drug Evaluation and Research, has said that expanded access protocols can produce data that demonstrate effectiveness in populations outside those studied in registration trials, potentially leading to broader indications.

Where is the self-interest for payers? They must first ask a difficult but crucial question: “Does the experimental treatment have a reasonable chance of a positive clinical impact?” After all, in our increasingly value-based world, should valuable health care resources be used with little hope of success? Within the context of expanded access and timeliness such a query sounds harsh relative to critically ill patients — and the issue of denying hope certainly resonates. So, how can this dilemma be resolved? Should a developer build into its expanded access protocol early-stage payer conversations to “pre-approve” reimbursement? If so, at what levels? Can third-party reimbursement go beyond the FDA-mandated limit of direct costs? This question becomes even more interesting if the expanded use patient is getting the experimental drug for a pre-off-label use, meaning that the approved study design is based on an endpoint for a different condition or conditions. Nobody said this was going to be easy.

Most important, what about the self-interest of the patient and (more broadly speaking) public health? The answer here is clear. For patients, expanded access is all about hope and the possibility of generating valuable evidence so others can benefit from their experiences. It’s here that we find the convergence of self-interest: more positive and predictive clinical outcomes, better data points for value-based reimbursement, and a broader and earlier understanding of benefit/risk ratios.

With all of these opportunities in mind, should we consider that expanded access programs become a “must do” for development programs seeking truncated approval pathways?

FDA Commissioner Scott Gottlieb said recently that drug companies have an “obligation to consider expanded access, especially in areas of unmet medical need.” Should payers be thinking the same thing? It’s time for the discussion about expanded access to get serious and, as Mark Twain reminds us, “The secret of getting ahead is getting started.”

Peter J. Pitts is president of the Center for Medicine in the Public Interest, a visiting professor at the Paris Descartes University Medical School, and a former FDA associate commissioner.

  • Jess you make it sound so good . But isn’t the bulk of that access from the original HIV activism ? It took Act Up protestors getting arrested at the FDA with that famous banner ” Silence Equals Death ” . In most of the the 30 years you cite the so called ” compassionate ” use approvals averaged about 2,000 a year . For all diseases in a country of 314 million . Sounds like a broken system to me. Maybe one only more pt protests can fix . Activists act . Advocates talk and talk

  • As a pt activist I am glad that the ” powers that be ” are hearing us more and more . We can do without the pejorative ” odor ” comments and move on . The FDA of the early 21st century had its own ” odor ” of arrogance and helped give birth to RTT. As we Pts have said to PHRMA . ” If you think your drug is good enough for early approval it’s good enough right now for compassionate use ” . Let’s start there . Jansen has stepped up and worked with NYU CUPA on a myeloma drug to show the way . And the current FDA , including some of the old guard , is not stuck on past resentments but moving forward . Will PHRMA respond ?

    • Note of clarification: FDA authorized Expanded Access programs have enrolled a quarter million people since the regulations were promulgated in 1987. It did not start with the example you cited. Leading the way were the first antiretroviral drugs 30 years ago, followed by large EA programs for targeted cancer therapies like Gleevec (8,000 patients under Expanded Access) and Iressa (24,000 patients under Expanded Access). Your example, though heavily cited and promoted, enrolled about 100 patients and only after clinical research was completed. It’s unclear why a third-party “request” evaluation would be needed if we launched more *early* access programs at meaningful size.

  • Great article Peter. Packed with the right questions and ideas. We have come a long way since FDA rejected our early proposals to make access programs work better in 2002 and 2003. Perhaps a quibble with your wording, but odor, and miasma when referring to Right to Try? The evolution of public and political thinking, and the resistance to change within medicine and the FDA, began even before our proposals to FDA 16 years ago. The evolution got a boost from our constitutional lawsuit, and another powerful boost, and a legal solution, from the Right to Try effort at the state and federal levels. Those efforts were in no small part about prying the access door open so it would then be necessary to start talking about things like how to pay for it. Now that is happening with no less an influencer than you encouraging the discussion. You were there at FDA when our proposals were first rejected. In fact you signed the letter. Not judging. It was different time, but referring to Right to Try has having an odor and being a miasma smacks of a “not invented here” attitude that has long permeated the insular culture of medicine. Our efforts and Right to Try are in major part why the public knows about this issue and why we are now, maybe, moving forward in material ways to make FDA’s programs work better. If that had happened twenty years ago we wouldn’t have filed our lawsuit, and if it had happened 10 years ago
    there never would have been a Right to Try movement. So I pose another question and challenge. Why did it take so long to get here? Why were petitions and lawsuits and state/federal legislation supported by decades of patient advocacy needed to move the needle? The inherent moral, medical and scientific possibilities of access have always been obvious, but the medical and regulatory establishment refused to acknowledge or even consider it as something positive that they should demanded. Instead, they fought it tooth and nail. Getting here had to be forced on the system from the outside. Medicine is advancing too quickly for change in how we deliver it to change so slowly. And as your article explains, we still have a lot to do to make FDA’s programs work as well as they need to, which they do not. Not even close. Thanks for proposing some good ideas. It has never been about the precise mechanism for us at the Abigail Alliance. It has been about changing minds, which has always been needed before real change happens. The public wants access to work, and the overwhelming support for Right to Try showed they weren’t satisfied with the glacially slow pace of change at FDA and within the medical community. It is not which mechanism is used to make it work that is of primary importance. It is that it is made to work. As you point out, the focus is now turning to the drug companies, as it was inevitably going to once the access door was legally pried open. They are the last big hurdle. My advice to them? The public wants this. If they want a material say in how it is going to happen, they should figure it out fast and start doing it. As Right to Try showed us, the public is out of patience on this one.

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