Take a chance on me

Right now, a few severely ill patients at University Hospital are waiting to hear if they’ll get a chance to try some of the world’s most cutting-edge experimental drugs or medical devices.

They’re hoping these unproven treatments might have some effect on their terminal cancers, severe infectious diseases, rare genetic conditions, or life-threatening injuries.

They also know the treatments might not help at all.

But patients are willing to take that chance, and, at U-M and other institutions, care teams are willing to offer them these last-ditch options because other types of care haven’t helped or have stopped working.

Such patients are the kind members of Congress had in mind when they introduced recent federal “Right-to-Try” legislation. Earlier this month, the Senate unanimously passed the bill, and the House might vote soon. President Donald Trump has signaled support for it.

If enacted, the bill will allow terminally ill patients nationwide access to unproven therapies outside of the existing U.S. Food and Drug Administration clinical trials framework. The legislation would extend “right to try” beyond the 37 states — including Michigan — that already have such laws in place, and provide a uniform framework for access.

But in fact, such a system already exists.

And more than 40 patients being treated at Michigan Medicine gained access to investigational products outside of clinical trials in 2016 alone, says Kevin Weatherwax, who leads the U-M team that helps make such access happen.

Expanded access at Michigan

Weatherwax and his U-M colleagues use the well-established Expanded Access program offered by the FDA to provide treatment to patients outside of clinical trials.

The program allows physicians to apply on behalf of patients for access to drugs and devices that aren’t yet ready for clinical trials, or that are in trials that the patients don’t qualify for.

“We’ve been supporting treating clinicians with expanded access requests for many years now, and last year was a banner year,” says Weatherwax, who heads a group in the Michigan Institute for Clinical & Health Research that prepares the applications.

“Most of these are life-and-death cases where patients have exhausted all available options, including rare diseases and extraordinary cases. And the FDA has always shown a willingness to review what we bring forward, approving all the cases U-M has requested in a timely way,” he says.

Helping patients and doctors navigate

Weatherwax’s team, funded by U-M and the NIH’s National Center for Advancing Translational Science, makes sense at a research university and advanced clinical care provider such as U-M.

For instance, the team worked with U-M engineers and pediatric surgeons to obtain Expanded Access approval for a 3-D-printed tracheal splint that it customizes to hold open the airways of toddlers born with malformed ones.

In the past three years, families have traveled hundreds of miles to C.S. Mott Children’s Hospital to have the splint inserted in their children’s airways. Researchers are tracking the children’s progress.

The research team is working toward opening a clinical trial that will study the impact of the splints in a group of future patients born with the same condition. But the FDA approval for Expanded Access to the splint on a case-by-case basis has allowed them to save young lives during the pendency of a clinical trial.

And the legislation, both in Michigan and the bill passed in the Senate, doesn’t address medical devices, just drugs, says Weatherwax. So children who have benefited from the 3-D-printed splints would not have been aided by “right to try.”

More important, he says, such bills in general don’t offer the same safety and cost protections that the Expanded Access program does.

Expanded Access requires review by a local Institutional Review Board, which ensures protections are in place for patient safety, including a mechanism to ensure that the language in the informed consent documents sufficiently and accurately conveys potential risks to the patient.

The FDA also sets out specific requirements about how companies providing products under Expanded Access should set costs. Generally, right-to-try bills haven’t laid out the same kinds of controls, nor have they required FDA review.

Barriers to access

Right now, the roadblock that Weatherwax and his colleagues at other major medical centers face when trying to get an Expanded Access approval for a patient isn’t these regulations, but rather the companies providing the drug or device.

Convincing companies to make a small batch of an expensive biological product for a single patient, or to dip into a small remaining supply of a clinical trial drug, can present a challenge. So can the negotiations between the lawyers from the company and the university over issues such as cost. Some startup companies are just too small to help.

This issue will still occur under any expansion of “right to try,” says Weatherwax. No legislation to date has included language that would compel companies to make products available to patients.

Moving forward

Regardless of the federal legislative actions, U-M will continue to engage with the FDA’s Expanded Access program and set guidelines and designate staff to help navigate the process and assist with negotiations with companies.

The Michigan Medicine Expanded Access Oversight Committee has worked to make the process even more efficient. Weatherwax co-chairs it, until recently working with professor emeritus Blake Roessler, M.D., and now with pediatric oncologist Raymond Hutchinson, M.D., M.S., who is also associate dean of regulatory affairs at the U-M Medical School.

Not all hospitals have such systems in place, but U-M is prepared to receive referrals for advanced care from across the upper Midwest and beyond.

“We have made a conscious decision to use the system that exists through the FDA, and we try to work with companies to make these options available, because they’re not treatments you can just pull off a shelf,” says Weatherwax.

“We use many resources to make drugs available for our patients even when restricted access or high cost create barriers,” says Andrew Shuman, M.D., M.Sc., an oncologist and bioethicist who chairs the institution’s Ethics and Medication Usage subcommittee.

“We have a formal process to help ensure that clinicians and patients are empowered to access recommended treatments equitably and fairly, no matter the regulatory framework. In addition, we are transparent in recognizing that any drug needs to be considered in light of its risks, especially when they might outweigh potential benefits. This requires ensuring that medications are being utilized in evidence-based ways in light of the clinical context.”

What might happen next

Enactment of national “right-to-try” legislation likely won’t speed up the process of getting products from clinical trials to widespread availability for all patients, Weatherwax predicts.

That’s because companies need clinical trial data, rather than information on solo patients treated under Expanded Access or “right to try,” to seek FDA approval and bring a product to market. Some critics of “right-to-try” legislation have said it could divert patients from clinical trials.

If the effort to pass “right-to-try” laws at the state and federal level has achieved anything, Weatherwax says, it’s raising awareness that patients and families can ask their care teams what else might be available to them. Getting a second opinion, searching for clinical trials, and asking to be referred to a teaching hospital, where clinical trials are more available, are all options patients should explore.

Michigan Medicine and other top academic medical centers have also begun to work together to help advance the use of the FDA’s Expanded Access program. They hope soon to share best practices, guidelines, and experiences with one another.

Another goal, Weatherwax notes, is to help medical researchers move beyond single-patient Expanded Access and broaden use of their new technology and ideas by launching small-group Expanded Access programs and clinical trials.

If multiple hospitals that each have a few cases of a rare disease each year could team up and arrange a cohort-based study, that would provide more information about how well the option works, compared with trying it in small numbers of patients at a single center.

Says Weatherwax, “As a nation, we need to be investing in helping people navigate the process of expanded access to innovative treatment.”

 

This story originally appeared at Michigan Medicine.