How companies decide whether to give experimental drugs to dying patients

Originally posted in the Washington Post by Ana Swanson

Joshua Hardy, an 8-year-old from Fredericksburg, Va., came very close to dying last March. He was battling a life-threatening infection that he developed after receiving a bone marrow stem cell transplant when his doctors recommended he try a medicine called Brincidofovir, then in the final phase of clinical trials.

There was a problem, however. The North Carolina company that makes the drug, Chimerix, refused to supply the experimental drug to the family. The company said it was devoting its resources to getting final Food and Drug Administration approval for the drug, which it argued would ultimately help the largest number of patients.

What happened next shattered the typical procedures for the industry. Hardy’s family reached out to followers on Facebook and Twitter, and the company received thousands of calls, messages and even death threats. People began inundating their government representatives with requests to help Josh. Chimerix agreed to include Josh in a late-stage study. Less than a month later, the little boy left the intensive care unit, and eventually went home.

Pharmaceutical companies are likely to face more questions over “compassionate use” — when severely or terminally ill patients are given access to treatment the FDA has not yet cleared — as desperate patients and their families turn to the Internet and social media to lobby for experimental care. While the FDA approves almost all compassionate use cases, the industry has handled the requests inconsistently.

But on Thursday, Johnson & Johnson, one of the largest drug companies, announced a new program that will try to impose more fairness and order to their decisions. The company appointed a prominent bioethicist, Arthur L. Caplan of the New York University School of Medicine, to create a panel of doctors, ethicists and patient advocates who will review hundreds of requests from patients and families like the Hardys and advise Johnson & Johnson on how to respond. Called the Compassionate-Use Advisory Committee, or CompAC, the program will be funded by the company but operate independently.

Amrit Ray, chief medical officer for Janssen Pharmaceutical Companies at Johnson & Johnson, said in an interview that the initiative aims to ensure that these decisions are more ethical and thoughtful, as well as to streamline the decision-making process. Patients who are eligible will be placed in open clinical trials, he said. If clinical trials aren’t available, the panel will consider the patient’s case quickly and make a recommendation to J&J, who will make the final decision about whether to offer the patient an experimental drug.

Ray said the decisions will follow widely established ethical principles, including that all patient requests are treated fairly and equally, and that serving patient requests doesn’t undermine the company’s ability to study the medicine’s potential benefits and carry it forward to final approval for sale to the public.

“What’s really unique is that this is the first time that independent external input is being sought on compassionate use requests, and our goal here is to make a real positive impact for patients,” Ray said in an interview. “Pre-approval access decisions are some of the most complicated and difficult that companies have to make.”

The Hardy case, while not directly related to J&J’s decision, was the most prominent example of social media influencing a company’s policies. During the media uproar, it was Caplan who called for an independent process like this one.

“A new system must be created to bring fairness, equality, and appropriate oversight to the availability of experimental treatments,” he wrote in the influential journal Health Affairs in an article co-authored with Chimerix chief executive Kenneth Moch. “The weight of such decisions should not and cannot rest solely on sponsoring companies.”

But some are skeptical of the new review panel, saying it won’t make it easier for desperate patients to get help. “What I think you have is J&J passing the buck on tough decision-making,” Darcy Olsen, chief executive of the advocacy group the Goldwater Institute, told the Wall Street Journal.

The libertarian institute has been pushing states to give patients access to experimental medicines without official approval. Since 2014, more than 20 states have introduced “Right to Try” laws, which allow drug companies and patients with terminal illnesses to bypass FDA approval. And some lawmakers are pushing to include similar measures for kids in 21st Century Cures, a forthcoming bipartisan initiative to streamline drug approvals and spur development.

But many ethicists argue there are difficult trade-offs in deciding whether to grant a patient access to an experimental drug. The Hardy family was able to harness social media and save his life, but many other patients don’t have the ability to do so. Companies, some say, also have limited resources, and the decision to devote time and money to providing drugs in an experimental stage could slow the drug’s final approval, perhaps resulting in more loss of life in the long run.

FDA approvals clearly lengthen the time it takes to develop a drug in the United States. After Congress began requiring the FDA to consider the safety and effectiveness of drugs based on controlled clinical trails in 1962, the average development time for a new drug rose from 2.5 years to eight years. In 1987, during the height of the AIDS epidemic, the FDA first began making an exception to this rule, allowing terminally ill patients to access experimental treatment.

In the Health Affairs article, Caplan and Moch argued that the FDA isn’t the problem, however. The FDA has withheld approval for compassionate use in just a handful of cases. Instead, company and investor concerns play a much more prominent role whether experimental treatments get approved, they write.

Often, companies don’t have a large supply of experimental treatments available, making decisions about who should receive a drug difficult.

The goal of the current system is to complete trials and make treatments available to the broadest number of people. Manufacturing experimental drugs, especially biological drugs, can be costly, and companies are often hesitant to charge patients for compassionate use, mostly because companies don’t want to reveal the price of the drug before they introduce it to the market.

Drug makers often only make enough of the drug to hold clinical trials, and they argue that diverting resources from clinical trials can delay the drug’s final approval, when it will have the potential to help a wider group of patients.

There are other concerns: Experimental drugs may be ineffective – or worse, compound the patient’s suffering and hasten their death. Doctors say Josh’s case is probably rare, and that the odds of an experimental therapy curing a patient are very small. And Moch and Caplan argue that a process that bypasses the FDA opens the door to allowing quacks, charlatans and others to exploit the severely ill with costly and ineffective interventions.

While Johnson & Johnson’s program is starting small — the panel will start by looking at a single medicine and expand only if that is successful — the company hopes that its program might provide an example for making these tough ethical decisions.

“Hopefully this will also be a model that can be followed more broadly in industry,” Ray said.