“Right to Try” Comes to the Federal Stage: What Stakeholders Should Do Now

On May 30, 2018, surrounded by patients directly impacted by tragic and intractable diseases, President Trump signed into law the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 (S. 204), which had passed the Senate on August 3, 2017 and then the House of Representatives on May 22, 2018 (following an unsuccessful attempt by the House to get an alternative bill, H.R. 5247, passed by the Senate this spring). The enacted federal “right to try” law follows the passage in 40 states thus far of similar state laws, a process put into motion by the Goldwater Institute, a libertarian organization in Arizona that developed the model “right to try” legislation on which most of the state laws are based.

On its face – and in the associated rhetoric – the federal “right to try” law provides a pathway through which patients may seek access to certain investigational drugs without FDA approval and also without IRB oversight. Proponents have argued that removing these oversight barriers will improve the speed with which seriously ill patients can access investigational products, while opponents have criticized “right to try” laws as offering patients false hope and increasing risks to patients. The impact of the federal law on stakeholders’ behavior remains to be seen.

What does the federal “right to try” law mean for:

  • Patients and their treating providers seeking to use investigational drugs outside of a clinical trial?
  • Institutions and IRBs accustomed to facilitating those investigational treatments?
  • The manufacturers of the sought-after drugs?

Below we outline some initial threshold considerations that stakeholders should evaluate in the wake of last week’s legislative change.

Access to Investigational Drugs for Treatment: Expanded Access vs. Right to Try

Access to investigational drugs in the United States is regulated by the FDA under the Food Drug and Cosmetic Act (“FDCA”). For the most part, individuals receive investigational drugs as participants in clinical investigations, which are conducted by sponsors under an FDA-issued Investigational New Drug application (“IND”). FDA may also permit select patients who do not qualify for access through clinical investigations to receive the investigational drugs for treatment purposes.1 This “expanded access” to investigational drugs is regulated by the FDA under 21 C.F.R. 312, Subpart I, and is available to patients who have a “serious or immediately life-threatening disease or condition” and no comparable or satisfactory alternative therapy available. A physician needs to certify – and the FDA needs to agree – that the risks are not unreasonable. The FDA must also find that providing the drug to a patient will not interfere with clinical investigations of the product. The FDA has undertaken several recent streamlining efforts to reduce the administrative burden associated with the expanded access program. Such efforts include, the issuance of a new Form 3926, in lieu of the Form 1571, to greatly reduce the paperwork time for physicians submitting single-patient emergency and non-emergency applications, and the ability for physicians submitting such applications to request that IRB review be accomplished by only one designated reviewer. In general, the data appear to demonstrate that FDA approves an extremely high percentage of expanded access submissions, and in a reasonable time-frame (with single-patient emergency requests turned around in less than a day, and single-patient non-emergency requests for drugs within three days2). Informed consent is required in accordance with FDA regulation.

The federal “right to try” law removes the FDA and IRB from the process, permitting (but, notably, not requiring) manufacturers to make certain “eligible investigational drugs” available to certain “eligible patients” without pre-approval by the FDA or IRB oversight. Like with expanded access, a treating provider needs to certify that the patient meets the stated eligibility criteria. Written informed consent to the treatment is also required, but unlike in the context of expanded access the elements are not specified. The law explicitly limits the federal government’s use of any clinical outcome data from treatment with investigational drugs through this pathway to delay or adversely affect the review or approval of such drug (although the FDA has also gone on record regarding the unlikelihood of adverse events that occur during expanded access influencing the drug approval process3), and it also provides explicit liability protection for manufacturers, sponsors, and others who provide the investigational drug. There is also explicitly no liability in connection with a decision not to make a drug available.

The chart below highlights the main differences between the federal “right to try” law and the FDA’s expanded access program:

FDA Expanded Access Drug Program Federal “Right To Try” Laws
Requires FDA Approval

x

Requires IRB Oversight

x

Requires Physician Approval

Requires Manufacturer Approval

Informed Consent Required

✔*

Reporting Obligations

✔*

Limitations on Liability

x

Restrictions on Use of Clinical Outcomes

x

Drug Must be in Development

x

*More robust requirements

Certain aspects of the federal “right to try” law remain unclear, and given the removal of the FDA from a direct oversight role, it is uncertain from where within the Department of Health and Human Services further guidance or regulation might come. Senator Ron Johnson, R-Wis., the sponsor of the legislation, sent a letter to the FDA Commissioner, Scott Gottlieb, after the bill was enacted rebuking the Commissioner for publicly suggesting that the law would require FDA to issue further regulations and guidance to protect patients, and candidly clarifying that the law intends to diminish the FDA’s power over people’s lives and that it, “is not meant to grant the FDA more power or enable the FDA to write new guidance, rules, or regulations that would limit the ability of an individual facing a life-threatening disease from accessing treatments.” Over the weekend, Commissioner Gottlieb issued a series of Tweets confirming the FDA’s commitment to its expanded access program and acknowledging the second pathway now available under the federal “right to try” law. The Commissioner indicated there would be an FDA work group convened to evaluate how to implement the “right to try” law to achieve its goals, noting: “The message is clear: Patients and families facing terminal illness want to be able to access promising drugs when they’ve exhausted available options.” He also recognized that the companies developing the drugs retain the “burden…to consider making these products available, pre-approval, to patients who qualify for access.”

Things Stakeholders Should Do Now

Only time will tell whether the federal “right to try” law will actually change the way in which patients access investigational drugs. Because this law establishes an additional alternative pathway to the existing FDA expanded access program, stakeholders – and, in particular, the companies that manufacture the investigational drugs – will exercise a lot of control over the extent to which the law is utilized. As noted, manufacturers are under no obligation to provide their drugs under the “right to try” pathway; therefore, they can decline patient requests entirely, require that requests be made only through the expanded access pathway, or impose additional conditions on the receipt of the drugs that may involve the FDA and other oversight functions to varying degrees. Similarly, treating providers, and the institutions at which they work, may voluntarily add requirements to the provision of investigational drugs through the “right to try” pathway, regardless of the existing regulatory framework. The form in which a patient request is made (expanded access vs. right to try) may inform, but does not dictate, the pathway through which access is accommodated, if it is at all.

In light of last week’s legislative change, we recommend that stakeholders do the following:

  • Manufacturers of investigational drugs for serious diseases or conditions should determine – in connection with the development of the expanded access policy required by the 21st Century Cures Act to be posted publicly – whether they are amenable to making their drugs available through the “right to try” pathway (in addition to, or in lieu of, FDA’s expanded access program). This could also include identifying additional requirements or protections that manufacturers will insist on, outside the regulatory framework of “right to try.”
  • Institutions should consult internally with IRB leadership, risk management, legal counsel, and treating physicians with experience with treating patients through FDA’s expanded access program to determine whether the institution will accommodate patients’ requests to pursue investigational products under the “right to try” pathway and, if so, whether to attach additional requirements.- Will institutions require IRB oversight for such uses regardless of the exemption under federal “right to try” law?- Will IRBs agree to play a role for “right to try” access where the law does not mandate IRB involvement?- If not IRB review, will institutions impose an alternative institutional review process (whether through an innovative care committee, or other type of internal risk and ethics review)?
  • All stakeholders should consider which terms in the agreements through which institutions receive investigational drugs to use for treatment purposes might be warranted in the “right to try” context that are different than those typically seen in the “expanded access” context?
  • All stakeholders should analyze any relevant state “right to try” laws to determine whether, in proceeding under either the expanded access or the federal right to try pathway, any additional state requirements might attach. This will involve evaluating the competing federal and state frameworks under a preemption analysis to determine what aspects of state law, if any, survive the two dueling federal pathways. The outcome of this analysis may assist stakeholders in determining whether one or the other pathway is a more attractive option (for example, under a hypothetical analysis, one might conclude that the expanded access pathway conflicts with the state “right to try” law, such that the state law is null and void; however, the federal “right to try” pathway may be in less conflict with a parallel state law, opening up the possibility of having to comply with the additional state requirements).
  • All stakeholders will have to evaluate what “written informed consent” will look like under the federal “right to try” law (if the stakeholder plans to accommodate or facilitate requests under this law). Potentially applicable state law requirements may influence this analysis. Stakeholders also have flexibility to determine by policy that certain information is material and should be included in such written consent, regardless of the law’s lack of specificity.

1 Investigational devices are also available through an expanded access program overseen by the FDA; this alert focuses on access to investigational drugs, as the federal “right to try” law does not address investigational devices.

2 See the United States Government Accountability Office’s Report titled “Investigational New Drugs: FDA Has Taken Steps to Improve the Expanded Access Program but Should Further Clarify How Adverse Events Data Are Used” GAO-17-564: Published: July 11, 2017; https://www.gao.gov/assets/690/685729.pdf

3 See “Expanded Access to Investigational Drugs for Treatment – Questions and Answers” Guidance for Industry, Issued June 2016, updated October 2017, https://www.fda.gov/downloads/drugs/guidances/ucm351261.pdfsee also Statement of Scott Gottlieb, M.D. before the Subcommittee on Health, Committee on Energy and Commerce, US House of Representatives, October 3, 2017, https://www.fda.gov/NewsEvents/Testimony/ucm578634.htm

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