Compassionate Use: Governing the Decision No One Wants to Make Wrongly
At some point, a clinical-stage company developing a drug for a serious disease will receive a request it is not fully prepared for. A patient — often dying, often having exhausted every approved option — wants access to the company's investigational drug outside of a clinical trial. Sometimes the request comes through a physician, sometimes through a patient advocacy organization, increasingly through social media and public pressure. It is one of the most human situations a company will face, and one of the hardest to govern well, because every instinct that makes us decent people pulls in a direction that a company cannot always responsibly follow.
This is the territory of compassionate use — known formally in the United States as expanded access — and it deserves a board's attention precisely because it is so easy to handle badly. Handled without forethought, it can expose a company to decisions made under acute emotional and public pressure, one request at a time, with no consistent principle, no operational readiness, and no clear view of the consequences for the drug's development. The board's role is not to decide individual cases. It is to ensure the company has a coherent, humane, defensible framework in place before the requests arrive — because they will arrive, and the worst time to think through the policy is in the middle of a heartbreaking specific case with a family and a journalist waiting for an answer.
What Expanded Access Actually Is
It is worth being precise about the mechanism, because the informal language obscures how much structure sits underneath it.
Expanded access is the regulatory pathway that lets a patient with a serious or life-threatening condition receive an investigational drug outside a clinical trial, when there is no comparable approved alternative and the patient cannot enroll in a trial. It is a treatment mechanism, not a research one — its purpose is to help a patient, not to generate controlled data. In the United States it operates under a defined regulatory framework, and it requires two independent agreements: the FDA must authorize the use, and the company that holds the investigational drug must agree to provide it. Neither can compel the other. The FDA authorizes the great majority of the requests it receives, which means that in practice the decisive gatekeeper is very often the company itself.
There is a separate, parallel pathway — the federal Right to Try Act — that allows eligible patients to request an eligible investigational drug from the manufacturer without the FDA authorization step. It is important for a board to understand that this pathway exists and differs procedurally, but the crucial point for governance is the same under both: in every case, the company must independently decide whether to supply its drug. The law does not force a company to say yes. The decision, and the responsibility for it, rests with the company. That is why this is a governance question and not merely a regulatory one.
Why This Is So Hard
The difficulty is that a compassionate use decision sits at the intersection of several legitimate considerations that genuinely conflict, and no framing makes the conflict disappear.
There is the moral pull, which is real and should not be rationalized away. A specific, identifiable person is suffering, has run out of options, and is asking for something the company physically possesses. Saying no to that is genuinely hard, and a company whose culture makes it easy has a different problem.
There is the clinical reality that the drug is investigational for a reason: its safety and efficacy are not established. A patient who is very ill — often too ill to have qualified for the trial — may be harmed rather than helped, and may be harmed in ways no one can yet predict. Compassion that ignores this is not actually compassion; it is the substitution of a feeling for a judgment.
There is the matter of supply. Investigational drugs are frequently manufactured in small quantities sufficient for the clinical program and no more. Diverting product to expanded access can, in a constrained situation, genuinely compete with the trials that represent the drug's path to helping far larger numbers of patients. This is an uncomfortable trade-off to state plainly, but a board that will not look at it is not governing.
And there is the consequence that boards most often fail to anticipate: adverse events that occur in expanded access use are real events involving real patients, and they can affect the development program. A serious adverse event in a very sick expanded-access patient — an event that might have nothing to do with the drug and everything to do with the patient's underlying illness — still happened while the patient was receiving the company's investigational product, and still has to be reckoned with. This is a documented and persistent concern among drug developers, serious enough that it has led some companies to hesitate to grant access at all. The regulator's position is that it is not aware of a case in which expanded-access adverse event data prevented a drug's approval, and expanded-access data has in some instances actually supported approvals. But the concern is not irrational, and it is exactly the kind of consideration a board should ensure management has thought through soberly rather than either ignoring or using as a convenient reason to refuse.
The reason all of this is hard is that the pressures are asymmetric in time. The moral pull is immediate, specific, and loud. The countervailing considerations — supply, development risk, the interests of the far larger population the trial is meant to serve — are diffuse, statistical, and quiet. A company deciding case by case under pressure will systematically overweight the visible and underweight the invisible. A framework decided in advance is how a company keeps faith with both the patient at the door and the thousands it cannot see.
The Board's Job: A Framework Before the First Request
The single most important thing a board can do here is ensure the company has a compassionate use policy in place before it is needed, and that the policy is coherent, humane, consistently applied, and honestly communicated.
A good policy answers, in advance and in general terms, the questions that are agonizing to answer in the specific: Under what circumstances will the company consider providing expanded access? What are the medical criteria a requesting patient must meet? How does a patient or physician actually make a request, and how quickly will the company respond? Who inside the company decides, and by what process? How does the company weigh requests against its supply and its trial obligations? The point of settling these in advance is not bureaucratic. It is that a principle chosen behind a veil of ignorance — before anyone knows which specific patient it will apply to — is fairer and more defensible than a decision improvised for a named individual under duress.
Consistency is itself an ethical requirement here, and one a board should specifically probe. A company that says yes to the patient whose family mounts a social media campaign and no to the equally deserving patient who suffers quietly has not been compassionate; it has been responsive to pressure, which is a different and worse thing. A policy exists partly to protect the company from making access a function of publicity rather than need. The board should ask not only whether a policy exists but whether it is actually applied evenhandedly, including to the cases that never make the news.
Transparency matters too. Federal law has pushed companies of a certain stage toward making their expanded access policies public, and beyond any legal requirement, a clear public policy serves patients and physicians who need to know how to ask and what to expect. A board should understand what the company communicates, and satisfy itself that the communication is honest — neither promising access the company cannot sustain nor hiding behind vagueness that leaves desperate families guessing.
The Questions a Board Should Ask
A board does not manage expanded access, but it should assure itself the company is ready. A few questions do most of the work.
Do we have a policy, and was it set before we were under pressure? A company that is writing its compassionate use policy in response to its first high-profile request is already behind, and is likely to produce a policy shaped by that single case rather than by principle. The board should want the framework in place early — ideally well before the drug is advanced enough to attract requests.
Is it applied consistently, including in the cases nobody is watching? The board should probe whether access tracks medical criteria or tracks publicity and pressure. This is the ethical heart of the matter, and it is invisible unless someone asks.
Have we thought honestly about supply? If the drug is manufactured in quantities matched to the trial, the board should understand what expanded access would cost the program, and ensure that trade-off is being weighed openly rather than used as an unexamined default reason to refuse.
Have we thought clearly about the development implications — without hiding behind them? The board should ensure management has soberly assessed how expanded-access safety data could interact with the development program, and has neither ignored the risk nor inflated it into a pretext. Both failures are common. The honest position acknowledges the concern, sizes it realistically against the regulator's actual track record, and does not let it silently become the reason the company says no to everyone.
Who decides, how fast, and does the process respect the reality that these patients do not have time? A policy that is humane in principle but takes six weeks to produce a decision for a patient with weeks to live is not humane in practice. The board should understand the actual response process and whether it moves at the speed the situation demands.
Are we being honest with patients and physicians about what we can and cannot do? Whatever the company's answer, patients and families deserve clarity and candor rather than false hope or bureaucratic evasion. The board should satisfy itself that the company communicates its decisions, including its refusals, with honesty and humanity.
The Traps
A few failure modes recur, and naming them helps a board recognize them.
Deciding case by case with no policy at all. This is the default failure, and it guarantees inconsistency, pressure-driven decisions, and a company perpetually reacting rather than governing. The absence of a policy is itself a policy — the worst one.
Using development risk as an unexamined shield. Because the concern about adverse-event data is real, it is available as a reason to refuse every request without ever honestly weighing it. A board should be alert to development risk being invoked reflexively rather than assessed, and should ask for the actual reasoning.
Letting publicity set policy. A company that grants access in proportion to the noise a case generates has outsourced its ethics to whoever is loudest. The board should treat a pattern of publicity-driven exceptions as a governance failure, not a series of individually defensible kindnesses.
Promising more than the company can sustain. In the desire to be compassionate, a company can create expectations — or an informal reputation for saying yes — that its supply and its obligations cannot actually support, setting up worse disappointments later. Humane governance is sustainable governance, not the most generous possible answer to the request in front of you.
The Underlying Principle
Compassionate use is where a clinical-stage company's humanity and its responsibilities meet most directly, and the temptation is to treat it as purely a matter of the heart. But the most compassionate thing a company can do is govern this well in advance: to decide, before any specific face is attached to the question, how it will weigh the patient at the door against the patients the trial exists to serve, how it will keep those decisions consistent and honest, and how it will move fast enough to matter.
The board's contribution is not to sit in judgment on individual requests, which it is not positioned to do. It is to insist that the company has done its thinking early, written it down, applied it fairly, and communicated it honestly — so that when the hardest requests come, and they will, the company answers from principle rather than from panic, and can look back on how it decided without regret regardless of what it decided.
This article addresses a sensitive area involving seriously ill patients. It is written for company directors as governance guidance and is not medical, legal, or regulatory advice; companies should work with qualified regulatory counsel and medical experts in designing an expanded access approach.
Lawrence Fine is CEO of AGCP Farmacêuticos and has advised on licensing, regulatory, and partnership strategy across the pharmaceutical and advanced materials sectors.