Federal “Right to Try” Legislation – Perpetuating a Misguided Skepticism Towards the FDA

Cross-posted from the CRITical Thinking blog.

By Jeanie Kim

The “right to try” (RTT) movement presents a narrative that pits patients against the FDA. Supporters of RTT, powered by the libertarian Goldwater Institute, have pushed for laws that let terminally ill patients bypass regulators to access unapproved treatments.

As of September 2017, 37 states have enacted RTT laws. Earlier this year, the Senate and the House introduced federal RTT bills, and on August 3, 2017, the Senate unanimously passed an amended RTT bill without an opportunity for debate. There is pressure on the House to follow suit, but it is unclear whether the House will consider the originally introduced RTT bill (“RTT 1.0”) or the Senate’s amended version (“RTT 2.0”), or even take up the legislation at all.

Despite the recent legislative backing, RTT is not a new concept. It is a variation on an age-old skepticism towards the FDA that has been around as long as the agency’s inception. At the core of RTT is the previously rejected, yet persistent argument that the FDA’s approval standards for safety and efficacy should not matter for terminally ill patients who have nothing to lose [1].The RTT bills are the latest tactic.  to undermine the FDA by suggesting that regulators are standing in the way of terminally ill patients. RTT 1.0 prohibits the FDA from interfering with “the production, manufacture, distribution, prescribing, or dispensing of an experimental [treatment]” that has passed initial safety testing on healthy volunteers and is intended for terminally ill patients who have exhausted medical options.

By adopting the premise that the FDA is a bureaucratic bottleneck, RTT misplaces the problem. The FDA has an efficient expanded access (EA) program for patients with life threatening conditions. Patients, in consultation with their physicians, can request access to experimental medicines from pharmaceutical companies. Once the company approves, patients can submit their applications to the FDA.

According to a recent report by the Government Accountability Office, of the nearly 5,800 EA requests received by the FDA from 2012 to 2015, the FDA allowed 99% to proceed, and for emergency single-patient requests, the agency typically responds within hours (p.17). (In many cases, the FDA provides feedback on dosage and other safety issues.)

These numbers show that the FDA is hardly a barrier.

RTT overlooks these facts and undermines a broader principle. Congress empowered the FDA with the scientific authority to evaluate clinical trial evidence and the regulatory authority to approve drugs for marketing. This dual grant of authority is based on the policy that companies should not be able to profit from medicines before proving that the medicines are safe and effective. Even the EA program operates within this framework – early access to unapproved drugs is carefully balanced against the need for information about a drug’s safety and efficacy.

RTT 1.0 contains provisions that could destabilize this system.

First, RTT 1.0 prohibits the FDA from using any clinical outcomes from RTT uses to negatively impact its review of a drug. This absolute bar removes the flexibility that the FDA needs to evaluate safety information. Under the current EA program, agency reviewers generally give little weight to adverse events that occur from EA uses but still have the scientific discretion to consider whether certain outcomes – such as unexpected organ failures – could be useful for future patients in similar situations (p.18).

Second, because the bill prohibits the FDA from interfering with the “distribution” of experimental treatments for terminally ill patients, RTT 1.0 leaves open the possibility of permitting companies to market unapproved drugs. The term “distribution,” which has various meanings [2], is not defined in the bill and thus, could be a camel’s nose for deregulatory efforts to loosen the FDA’s prohibition on selling unapproved treatments.

Together, these two aspects of RTT 1.0 not only remove basic safeguards for current patients seeking access to experimental treatments but also undermine the research process that ensures that future patients will have access to drugs that are proven to be safe and effective. The removal of regulatory oversight is all the more problematic because RTT 1.0 also shields companies from all liability associated with RTT uses.

The Senate made attempts to address these concerns in its amended bill. First, while RTT 2.0 still prohibits the FDA from using clinical outcomes from RTT uses, the amended bill makes an exception for cases where it would be “critical” to determining the safety profile of a drug.

Second, RTT 2.0 requires manufacturers to adhere to FDA regulations concerning experimental treatments – specifically, regulations that prohibit companies from commercially distributing and promoting experimental drugs [3] and from charging more than “direct costs” for experimental drugs [4].

The amended bill also does not release companies from liability if there was reckless or willful conduct or gross negligence.

A side-by-side comparison of the two RTT bills shows that RTT 2.0 includes several provisions intended to protect patients and maintain some regulatory oversight.

Issue RTT 1.0 RTT 2.0
Can FDA consider clinical outcomes from RTT uses? No No, unless the outcomes are critical to determining the safety profile of the drug
Can companies commercially distribute and profit from experimental drugs? Ambiguous; because “distribution” is permitted, it could allow companies to market and charge high costs for experimental drugs No, companies cannot commercial distribute, promote, or charge more than “direct costs” for experimental drugs (but this provision is linked to FDA regulations which can be changed by the agency)
Are there reporting requirements for RTT uses? None Companies must submit annual summaries of all RTT uses to the FDA; the FDA must post annual summaries of all reported RTT uses and indicate which clinical outcomes were used
Manufacturer liability? No liability for any harms No liability, unless reckless or willful conduct or gross negligence
What effect would an FDA-issued clinical hold have on RTT uses? None Experimental drug or biologic would not eligible for RTT use during an FDA-issued clinical hold
Written informed consent requirement? None Patients must provide written informed consent to the treating physician
Prohibition on physician compensation? None Physician certifying RTT use cannot be directly compensated by manufacturers of the experimental drug

The comparison also reveals just how detrimental RTT 1.0 could be, particularly for patient safety, as the original RTT bill would leave patients vulnerable to opportunistic behaviors by companies and physicians.

However, despite these improvements, RTT 2.0 is still based on the same misguided premise of RTT 1.0 – that the FDA is a barrier – and the same skepticism towards the FDA. Under RTT 2.0, RTT is intended to act as “an alternative pathway alongside [the EA program]” such that both pathways are available for patients with “life-threatening diseases or conditions.” The only difference is that the EA pathway preserves the FDA’s role and the RTT pathway minimizes it. While RTT 1.0 is a swift blow to the FDA, RTT 2.0 sets the stage for a gradual weakening of the agency’s scientific and regulatory authority.

For an example, RTT 2.0 does not expressly prohibit companies from selling unapproved drugs but cites FDA regulations for experimental drugs. This presents a loophole where the FDA can be pressured into loosening its regulations on experimental drugs in the same way as under RTT 1.0. Given the current antiregulatory climate, this is not far-fetched. In fact, a former president of Goldwater Institute has suggested that allowing companies to profit from experimental treatments is aligned with the end goals of the RTT movement [5].

Finally, adding to the point that RTT is merely a shell for antiregulatory sentiments, neither RTT bill would actually improve patient access to experimental drugs. Many of the patient-centered additions in RTT 2.0—such as the transparency and reporting requirements for companies and the FDA—could easily be incorporated into the EA program without legislative action and without removing the FDA’s oversight.

Unsurprisingly, the RTT bills fail to deliver on its promise to streamline patient access to experimental treatments because they remove a “hurdle” that is not much of a hurdle for patients in the first place, but a critical component of the drug development process.

Other barriers for patients exist. Companies, who are the initial decision makers, are generally reluctant to grant access to unapproved treatments. And even after getting EA approval, patients must be able to afford the costs as payers typically do not cover unapproved treatments.

These issues are multifaceted and much more complex than the “solution” that RTT offers. Patient access to experimental treatments can be improved under the current EA program while maintaining the overall regulatory structure that balances access with safety and efficacy. In fact, there are already efforts to increase the transparency of companies’ EA policies and address other legitimate barriers. True solutions will require collaboration from regulators, manufacturers, and patients, and the FDA is best suited to facilitate improvements that will benefit both present and future patients.

Jeanie Kim is a research fellow at Yale Law School and the Collaboration for Research Integrity and Transparency (CRIT).

 

[1] The Supreme Court rejected the argument that terminally patients have the right to access unapproved treatments. U.S v. Rutherford, 442 U.S. 544 (1979); see also Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, 495 F.3d 695 (D.C. Cir. 2007), cert denied 552 U.S. 1159 (2008). Contrary to the optimism of the RTT movement, 90% of drugs that enter the first phase of clinical testing do not receive approval because of unexpected toxicity or lack of effectiveness, and even drugs that show promise in Phase 2 clinical trials are often not confirmed by Phase 3 trials. Katarzyna Smietana et al., Trends in clinical success rates, 15 Nature Reviews Drug Discovery 379 (2016), doi: 10.1038/nrd.2016.85; U.S. Food and Drug Admin, 22 Case Studies where Phase 2 and Phase 3 Trials has Divergent Results, January 2017, available at link (accessed September 8, 2017).

[2] Under current FDA regulations, “distribution” is defined as “to sell, offer to sell, deliver, or offer to deliver a drug to a recipient.” 21 C.F.R. § 203.3(h).

[3] 21 C.F.R. § 312.7.

[4] 21 C.F.R. § 312.8(d)(1).

[5] Darcy Olsen, The Right to Try: How the Federal Government Prevents Americans from Getting the Lifesaving Treatments They Need 205-206 (2015) (then-president of Goldwater Institute stated that “[a]llowing companies to charge for investigational drugs would make compassionate use instantly more attractive [for companies]”).

 

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