Is there better way to allow access to experimental drugs?

How Far Do You Go When the Alternative Is Death?

May 12, 2022, 5:00 a.m. ET

By Daniela J. Lamas, NY Times

Dr. Lamas, a contributing Opinion writer, is a pulmonary and critical-care physician at Brigham and Women’s Hospital in Boston.

My patient was so close. After emails to politicians and pharmaceutical executives, after a social media campaign and months spent swinging between hope and fear, Michael Forbes had won. A drug company decided that he could receive a new, unapproved drug for advanced lung cancer that might prolong his life. When the news came, his family posted a video of Mr. Forbes, 55, dancing to “Lovely Day” on a balcony overlooking the ocean.

But just weeks later, he was intubated in our intensive care unit. While the investigational treatment was going through the requisite paperwork and protocols before it could reach him, he had grown sicker. And if he did not improve enough to breathe without a ventilator, it would be too late. Could it all end here?

Though there are infinite permutations of tragedy in the hospital, health care workers do not often care for someone who is so close to receiving a medication that is just out of reach. But this scenario is likely to become more common as an ever-growing range of treatments — immunotherapy and gene therapy among them — push the boundaries of living with disease and offer patients and families hope.

Getting early access to an experimental drug often requires enrollment in a clinical trial where it’s being tested. Those who are not eligible for a trial and have run out of other treatment options may turn to the Food and Drug Administration’s expanded-access process to receive these promising but unapproved treatments — if the drug company agrees.

The fight for expanded access is a fight for more time. It is a balance between possibility just beyond the horizon and harsh reality, between the instinct to rescue an individual and the need to protect resources for the clinical trials that are the only route to drug approval.

The expanded-access process (sometimes called compassionate use) has been around in some form for decades and has long brought with it a host of murky ethical issues. Desperate patients and families often end up waging media campaigns if the drug company initially denies a request — which they do for a host of reasons, such as inadequate supply, the concern that a patient is too sick to benefit and the largely unfounded worry that a negative outcome could place the drug’s future approval in jeopardy.

Of course, there are cases where pursuing an investigational drug is not the right choice. Even when someone is facing death, there can still be harm. But who should decide whether someone with a terminal illness gets one more shot, however long the odds?

Mr. Forbes’s ordeal began in 2018 when he felt something in his chest and soon after learned that he had Stage 4 lung cancer. When he was in pharmacy school, that diagnosis meant death within months. Now, with new drugs that could target cancers like his, he could plan for a year. Maybe more.

As the years passed, Mr. Forbes and his wife, Alice Forbes, grew cautiously optimistic as he responded to treatment. But then the cancer progressed through multiple therapies. With standard treatment options exhausted, in 2021 his oncologist mentioned a trial of a new drug for patients with his specific lung cancer mutation. In early studies, about 40 percent of patients saw their cancers shrink, an effect that lasted for about seven months. This was not a cure, but for someone who is terminally ill, seven good months could sound like a lifetime.

The family pinned their hopes on this drug. So when they learned that the clinical trials were no longer enrolling new participants, they turned to expanded access — but drug companies do not offer this pathway for all their products, particularly those with only preliminary data available or limited supply, and this specific drug had no such option. His oncologist made requests to the drug company anyway, but was denied.

In response, his family marshaled their resources, reaching out to friends and relatives across the country. The head of the drug company must have received more than a hundred emails begging him to make an exception. They started a petition on change.org and wrote to politicians and others who might be able to apply pressure. Not long after, the drug company agreed to make an exception and allow Mr. Forbes to receive the drug through a single patient protocol, which is essentially a clinical trial written for one person.

Then he waited, first for his oncologist to write the protocol and then for that to be approved by the hospital and the F.D.A. to ensure that the drug would be administered safely. This would take around six weeks, and in that time his health deteriorated and that’s when he became my patient.

As his oxygen levels teetered, I thought about the heartbreaking decisions his family would now face. Continuing to chase the possibility of this drug now would only prolong our patient’s suffering.

Though Ms. Forbes briefly wondered whether she could just keep her husband on the ventilator until the drug arrived, she knew that was not what he wanted. He had agreed to the breathing tube if there was a reasonable chance of recovery, but that was no longer possible. Even if his oncologist had the drug on hand, Mr. Forbes was now too sick to tolerate it. Knowing that her husband would never again be able to enjoy the things he had loved, that his death was inevitable, his wife chose to make sure that he was comfortable. He died just three days after I met him, and she was at his side.

It is tempting to think that my patient could still be alive had he received the drug sooner, but it is impossible to know what would have happened. I have to wonder, as his family did, if there’s a better way.

There have been many attempts to improve the process. The much-publicized and controversial national Right to Try Act of 2018 allows patients and doctors to ask drug companies directly for access to unapproved treatments, without involving the F.D.A. Some experts argue that this was shortsighted; the F.D.A. does not appear to be the stumbling block. The agency approves nearly all such requests that come through, within hours or days, and can offer important safeguards.

Instead, often the main hurdle, as the Forbes family observed, is whether the drug company has an expanded-access program for a specific drug and if it does, whether it approves the request. There is no requirement for companies to report how many requests they accept, though some larger drug companies make this information public.

Perhaps more important, it’s unknown to what extent families’ media campaigns affect these decisions. This is what troubles Arthur Caplan, a professor of bioethics at New York University’s Grossman School of Medicine. “If you have resources, then you hire PR people, you build your own website, and you have a pretty good chance of guilting or shaming the company into providing something to you,” he told me. “I understand why people do it, but it’s hardly an equitable system.”

Dr. Caplan has pioneered a possible solution. Working with Janssen Pharmaceuticals, a part of Johnson & Johnson, he heads an advisory committee of physicians, ethicists and community members who evaluate these requests and then develop a recommendation for the drug company. Much like the U.S. system for organ allocation, which Dr. Caplan also helped develop, this committee aims to ensure a fair allocation of a limited resource. Drug companies should not be swayed to say yes by the most sympathetic photos or pushed to say no because of a concern that a negative outcome could impact consumer confidence in a drug. Instead, the committee applies consistent criteria to each anonymous potential recipient and renders a decision based on medical factors rather than the pathos of a personal story, wealth or media prominence.

This is a start, particularly when coupled with better tracking of outcomes and improved education for clinicians about how to enroll their patients in clinical trials and navigate expanded access if those trials aren’t a possibility. A lawyer by training, Ms. Forbes did most of this navigation and advocacy on her own, but there are many families for whom that would not be possible. And when clinicians’ time is a limited resource, how much of this process can they realistically take on for a drug not yet proved to work?

That is the question behind so much of this conversation. How far do we go when the alternative is death? And what is sacrificed in the process? “You’re holding out hope that you might be that rare one, that if you can just stay alive long enough for the next drug, that might change things,” Ms. Forbes told me, reflecting on those final weeks.

Even though her husband never did receive the expanded-access drug, she does not regret that they devoted so much of their remaining time and effort to pursuing it. They believed that this medication would work, she said, but they were also able to consider a reality where Mr. Forbes did not live to see it.

“Despite how it all ended, it was good for Michael to feel positive and hopeful,” she said. “It was very good for me, because there was no stone unturned.” That is not the type of victory they wanted, but it is something.