Social media campaigns have successfully pressured drug companies to approve some requests for investigational drugs for terminally ill patients under expanded access programs (EAPs), but this raises significant ethical concerns, experts say.
“The success of social media campaigns, in most cases, both relies on and fosters public misunderstanding of the limited evidence for the safety and efficacy of drugs early in their development process,” says Steven Joffe, MD, MPH, vice chair of the Department of Medical Ethics and Health Policy at University of Pennsylvania Perelman School of Medicine in Philadelphia.
One ethical concern is that patients who lack knowledge of how to leverage social media are at a disadvantage. “One shouldn’t have to rely on how social media savvy one is, to gain access,” says Peter C. Adamson, MD, chair of the Children’s Oncology Group and Alan R. Cohen endowed chair in pediatrics at the Children’s Hospital of Philadelphia.
One argument in favor of expanded access is that patients, with the advice of their doctors, should be able to decide how to weigh the potential benefits, risks, and uncertainty for themselves. “Many argue that it’s unreasonably paternalistic not to give patients, particularly those with life-threatening diseases, the right to make these choices for themselves,” says Joffe. On the other hand, he says, early access fosters false hopes. This could divert patients from more beneficial treatments, including excellent palliative care, he says.
Here are some other ethical concerns that experts have:
• Investigational drugs may be unsafe for patients. “Compassionate use programs must balance safe and speedy market entry for current and future patients with the immediate needs of patients who may not survive the drug development period,” says Valarie Blake, JD, associate professor of law at West Virginia University College of Law in Morgantown. Blake is a former ethics senior research associate at the American Medical Association.
“For the individual patient, compassionate use represents hope and a chance at survival, however small and unpredictable,” says Blake. “But it may come at a heavy price if the unapproved therapy shortens the patient’s life or mars it with harmful side effects.”
EAPs are premised on a belief that access to unproven drugs is medically beneficial. “In reality, most drugs put into clinical development never prove safe and effective. Even those few drugs that do prove safe and effective often confer marginal benefits,” says Jonathan Kimmelman, PhD, associate professor in the Biomedical Ethics Unit at McGill University in Montreal, Canada.
“If the drug is in early phase testing, it’s likely that little evidence exists,” says Joffe. “Is it reasonable to treat patients with the drug on the basis of very little evidence?”
Phase 1 trials usually cannot establish what serious side effects may result from the medication or what long-term consequences of use of the medication may be. Thus, “it is debatable whether any patient can be informed as to the consequences of their actions,” says Steven S. Ivy, MDiv, PhD, senior vice president of values, ethics, social responsibility, and pastoral services at Indiana University Health in Indianapolis.
• EAPs can threaten clinical trials by giving patients a pathway to avoid trials designed to rigorously evaluate the new drug. “The possibility of eroding the value of research is disturbing,” says Ivy.
This is particularly a problem for randomized trials, says Joffe, in which patients have a chance — usually 50% — of not getting the new drug.
“The most important thing in drug development is to rapidly and accurately evaluate the safety and efficacy of a new drug, so that safe, effective drugs can be made available to the public,” says Joffe. “Anything that threatens or slows this is bad for the public health.”
George J. Annas, JD, MPH, William Fairfield Warren Distinguished Professor and chair of the Department of Health Law, Bioethics & Human Rights at Boston University, says “compassionate use of drugs that have no proven efficacy by patients who are dying and believe — wrongly — that they have ‘nothing to lose’ by trying them is a major problem for drug companies.”
To the extent that people who might otherwise become subjects in their trials get access to the active drug, instead of taking their chances in a clinical trial, says Annas, “the trials will be much harder to do, and much slower to get a result.”
Adamson doesn’t see the threat to research as a valid reason for a drug company not to have an EAP, however. “Ideally, you do want patients to participate in clinical trials if they are willing and eligible to enroll. You wouldn’t want to see accrual to the trials suffer because of compassionate access programs,” he says. “But I’m not aware of any situation like that that has actually happened.”
The pressure and reputational risk arising from social media campaigns “can be impossible to resist, overwhelming all other legitimate considerations,” says Joffe.
Denying a patient’s request can become a public relations disaster. “The drug companies haven’t been able to take the publicity heat when it is turned up by a social media campaign on behalf of a dying person,” says Annas. “The drug company can be made out to look heartless, and even evil.”
Compassionate use requests depict science as bureaucratic red tape, adds Ivy. “It is difficult to justify denying even a sliver of hope to the terminally ill,” he says. “To watch a patient suffer and die while the possibility of treatment is available seems cruel beyond measure.”
Adamson says that clear guidelines are needed on when a therapy will be made available. “If a therapy is truly potentially life-saving, I think the bar to get access to that therapy ought to be lower,” he notes. “A lifesaving anti-infective and an early phase cancer drug are not the same.”
Advocating for the patient is the physician’s job, says Adamson. “Finding a way to allow for realistic hope is part of what oncologists do,” he says. “It is not frequent, but there are times when that would include access to a novel agent through an EAP.”
The reality is that people will continue to die of potentially curable diseases unless drug companies and others do the research needed to develop cures, says Annas. “Making experimental drugs available outside a clinical protocol simply lengthens this process,” he says. “It is, I think, morally sound not to have any exceptions to drug trial protocols.”
Some states have passed “right to try” laws allowing terminally ill patients to receive experimental drugs and devices after they have completed phase 1 testing. “Expanding access to unproven drugs to populations that are otherwise ineligible for trial participation can result in unexpected safety issues,” says Kimmelman. “This could derail otherwise promising drugs from being developed.”
Right to try laws threaten the drug development process by undermining clinical trials, says Joffe, and are based on a misunderstanding of the risks, benefits, and uncertainties of expanded access. “They are part of a general antiregulatory effort to undermine the FDA’s authority and ability to ensure efficacy before drugs are marketed,” he says.
The laws increase the risk that patients will receive drugs that are unsafe and/or ineffective, according to Joffe. “They are inconsistent with a fundamental presumption that there should be evidence that drugs are effective before they are sold in the marketplace,” he says.
Right to try laws fail to address a broader issue, says Blake: that the public feels that drugs aren’t making it to the market fast enough. “We have to evaluate how much delay we can accept, and at what loss of safety — and what other mechanisms can be put in place to speed drug access for everyone, not just a few,” she says.
Right to try laws “make for good rhetoric,” says Kimmelman. “But when you look at the science and law surrounding drug development, there is little about such policies that genuinely advance the needs of patients, research systems, or healthcare systems.”
- Peter C. Adamson, MD, Chair, Children’s Oncology Group, Alan R. Cohen Endowed Chair in Pediatrics, The Children’s Hospital of Philadelphia. Phone: (215) 590-6359. Fax: (215) 590-7544. Email: firstname.lastname@example.org.
- George J. Annas, JD, MPH, William Fairfield Warren Distinguished Professor and Chair, Department of Health Law, Bioethics & Human Rights, Boston University. Phone: (617) 638-4626. Fax: (617) 414-1464. Email: email@example.com.
- Valarie K. Blake, JD, MA, Associate Professor of Law, West Virginia University College of Law, Morgantown. Email: firstname.lastname@example.org
- Steven S. Ivy, MDiv, PhD, Senior Vice President, Values, Ethics, Social Responsibility, and Pastoral Services, Indiana University Health, Indianapolis. Phone: (317) 962-3591. Email: email@example.com.
- Steven Joffe, MD, MPH, Emanuel and Robert Hart Associate Professor, Vice-Chair, Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia. Phone: (215) 898-3055. Fax: (215) 573-3036. Email: firstname.lastname@example.org.
- Jonathan Kimmelman, PhD, Associate Professor, Biomedical Ethics Unit, McGill University, Montreal, Canada. Phone: (514) 398-3306. Fax: (514) 398-8349. Email: email@example.com.