It's a busy time to be a bioethicist, thanks to the passage of right-to-try bills in several states, the introduction of federal right-to-try legislation and the onslaught of social media campaigns seeking patient access to experimental drugs.

It's perhaps the latter that causes the phone to ring the most. "We're getting calls from companies asking for advice on how they should respond" to compassionate use requests, said Arthur Caplan, director of the Division of Medical Ethics at NYU Langone Medical Center, who earlier this year was named to a first-of-its-kind committee for Johnson & Johnson, convened to advise the big pharma on compassionate use requests.

To date, getting terminally ill patients access to an investigational drug has been kind of a haphazard occurrence.

Recently, social media has been the biggest driver, Caplan acknowledged, including some "highly visible social media campaigns" that have proved efficacious for getting a dying patient access to an investigational therapy. "But they're not very fair," he added. Patients who are less internet-savvy or who fear a loss of privacy won't benefit. And, even then, "social media only works for so long and then it's not newsworthy.

"So if you're the sixth social media campaign of the month, you might be very deserving, but you're not going to get the pull," he said.

David Farber, partner in the FDA/life sciences practice at King & Spalding, was even more critical, calling social media "too blunt a tool" for something as complicated as determining whether a particular individual should receive a particular investigational treatment. Administering an unproven drug or biologic to a very sick patient is "truly a roll of the dice; you can just as easily kill someone as save them. Social media does not allow for any of the nuance to come through," Farber added.

The need is there for a standardized process for patients and physicians to research and apply for early access to potentially life-saving drugs – as is the need for clear guidance for companies fielding compassionate use requests. And meeting those needs may have been the intent of the right-to-try laws that have so far cropped up in 24 states, but the truth is all fall short of their promise and leave dangling ethical questions to boot.

STATE LAWS HAVE CHANGED NOTHING?

Caplan and Farber hosted a conference call for media recently to discuss the issues of right-to-try laws. The impetus was the July introduction of H.R. 3012, the Right to Try Act of 2015, by Reps. Matt Salmon (R-Ariz.), Paul Gosar (R-Ariz.) and Marlin Stutzman (R-Ind.) that would make it the law of the land to expand access of experimental drugs to terminally ill patients who have prescriptions from their doctors, essentially by preventing the FDA from restricting such access.

The FDA has had a path in place since the 1990s allowing for early access to drugs, though a 2007 appellate court decision, Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, ruled that patients do not have the right to a potentially toxic therapy with no proven therapeutic benefit.

But, as Caplan and Farber pointed out, the FDA hasn't really been the barrier to patient access as many have claimed. The agency, they noted, grants roughly 99 percent of expanded access requests. Of a total 1,882 expanded access investigational new drug application requests submitted to the Center for Drug Evaluation and Research between Oct. 1, 2013, and Sept. 30, 2014, 1,873 of those were allowed to proceed.

"We've been looking at this and we see the FDA is pretty responsive," Caplan said.

So it's not immediately clear what a federal law would do. Existing state laws vary; to some degree, most are similar in the general requirements, according to Caplan. Those include terminal patients – though he pointed to seven states that included indications that would leave the patient in a vegetative state – and also require a doctor's prescription. Drugs sought for compassionate use must also have at least passed through phase I.

What those laws don't do, however, is assist in patient access to early drugs in any practical way. They do not dictate which entity is obligated to pay for the treatment, and nothing is set up to cover any travel or lodging that might be required with treatment administration. "So we've become a little skeptical [of right to try] because there's nothing in the laws to facilitate a person's ability to do so," Caplan said.

"I think it's fair to say we haven't yet found the case where the right-to-try law helps getting access to anything." He added later that he's heard from pharma execs who said the right-to-try laws "are well intentioned, but they don't change a single thing" in terms of patient access at their companies.

Nor do the laws obligate any specific institution, including the FDA, to allow access. That means the decision would fall primarily to the companies, and companies – particularly the small firms that might get overwhelmed by a flood of compassionate use requests – have reasons for not wanting drugs administered to very sick patients.

Last November, for example, Cytrx Corp. saw the FDA slap a partial clinical hold, stopping new patient enrollment in studies testing cancer drug aldoxorubicin because of the death of a patient receiving the drug on a compassionate-use basis. In that case, the company was able to resolve the issues, with the FDA removing the hold in January, and ended up reporting little to no impact on its timelines.

But companies are especially wary that adverse events in compassionate use setting may be held against the drugs when they try to seek approval and they "have to spend time explaining to the FDA," Caplan said.

"It can also make investors nervous," he added, which is particularly frightening for the smaller firms with small cash balances.

Still, the fact that 24 states have passed right-to-try laws – more are expected – and federal legislation has been introduced indicates that Americans "do want something done to make it easier for desperately ill people [to get access to drugs] earlier in the process," Caplan said.

But some ethical questions remain.

WHERE BIOETHICS COMES IN

One issue both Caplan and Farber pondered is whether it is ethically responsible to allow access to drugs at the phase I stage. Often, initial phase I trials are designed to evaluate safety only – sometimes in healthy volunteers rather than patients – and they provide no dosing data, no efficacy signal.

"We all need to appreciate how early stage phase I is, and it is very early stage," Farber said. "Phase I usually happens years before FDA approval in the normal approval pathway." By allowing access so early, "we may be enabling a worst-case scenario."

At that early stage, companies also are more liable to stop development for a host of reasons ranging from a lack of substantial enough efficacy, changes in regulatory pathways and shifting market landscapes. Or a company could simply run out of money. That's "just a reality of development and how the drug process works," Caplan said.

He also noted that some of the state laws highlight other worries. Right-to-try laws for 13 states, for instance, say hospice care can be withdrawn if patients receive experimental treatments; in four states home health care can be denied; and one state excludes minors from benefitting from right to try.

And should only patients who are terminal be allowed early access? Caplan pointed to patients suffering from progressive or degenerative diseases such as multiple sclerosis or macular degeneration. Is it fair to block those patients from access to a potentially helpful early stage therapy?

Another consideration is how patients and their doctors find out about potential drugs for expanded access. Some companies post clear information on their websites; others leave it to patients to track down on clinicaltrials.gov, which, as Caplan noted, is not the most navigable site for a non-industry person. There are some patient groups that gather information, "but there are still a lot of headaches out there."

Those and other issues are likely to come up if Congress takes up the Right to Try Act of 2015 legislation when it returns from recess, and Caplan said he believes it will, given all the interest at the state level.

"I think we'll hear it discussed in the upcoming legislative session."