How Federal Preemption (or Lack Thereof) Could Influence the Use of Federal “Right to Try”
As discussed in our Alert of June 4, “Right to Try” Comes to the Federal Stage: What Stakeholders Should Do Now, manufacturers, patients, providers and IRBs are now grappling with two alternative federal pathways through which manufacturers may (but are not required) to provide investigational drugs for treatment purposes outside of an FDA-overseen clinical investigation. As manufacturers, treating physicians, institutions, and other stakeholders pause to consider whether to accommodate or facilitate access through the federal “right to try” law, we explore some of the factors that may influence this decision. In particular, this Alert examines the continuing force of the forty (40) enacted state “right to try” laws in relation to the new federal “right to try” law. Ironically, manufacturers seeking to avoid patchwork regulation may conclude that federal “right to try” could increase, rather than decrease, the number of requirements they need to address when voluntarily providing access.
It bears reiterating that none of the available pathways through which investigational drugs may be provided for treatment purposes (FDA’s expanded access pathway, federal “right to try” or state “right to try”) entitles patients to receive these drugs or compels manufacturers to make their drugs available for treatment purposes outside of an available clinical investigation. They are optional, their requirements triggered only if a manufacturer decides to make a drug available to a specific patient or patient population.
Factors That May Influence Stakeholders’ Behavior
Various differences between the FDA’s expanded access pathway and the new federal “right to try” pathway may influence stakeholders’ behavior. Factors in the new federal “right to try” law that might appeal to manufacturers and physicians attempting to secure access on behalf of their patients include:
Less bureaucratic oversight (no mandated FDA or IRB oversight);
Explicit liability protection (particularly for manufacturers and sponsors, where there is not even an exception for gross negligence, reckless or willful misconduct, or intentional torts, as is the case for certain other players); and
- Legislated limits on how the federal government may use clinical outcomes data.
However, it is difficult to predict whether any of these factors would change manufacturers’ position on how, if at all, they provide access to investigational drugs for treatment.1 With respect to reduced bureaucracy, most data suggest that the FDA’s approval rate and response time-frame are not an obstacle to access. Furthermore, the FDA’s recent streamlining efforts include an option for physicians to request delegated review by a single IRB member when reviewing requests for single-patient expanded access treatments. Although liability protection seems like a bonus to manufacturers, given the dearth of litigation by patients who have received investigation drugs through expanded access (and contractual limitations of liability established through most expanded access agreements between manufacturers and providers), it is unclear if liability concerns are critical for manufacturers. Finally, although it might appear that manufacturers stand to benefit from the assurance that any adverse events experienced as a result of treatment with investigational products will not thwart approval, the FDA has been clear in both recent guidance2 and statements by Commissioner Gottlieb in Congressional testimony3 that this is already an illusory concern.
Even assuming the three factors listed above could influence manufacturers or providers to prefer federal “right to try” over the FDA’s expanded access program, the balance may yet tip in favor of expanded access as a result of a factor to be examined below, namely, the tremendous uncertainty surrounding the governing law when federal “right to try” overlays a state “right to try” statute.
Federal Preemption of State Laws
The Supremacy Clause of the United States Constitution makes federal law “the Supreme Law of the Land,”4 and thus “prevents the states from impinging overmuch on federal law and policy.”5 Federal preemption may be express (written into the Congressional statute), or implied through either “field” or “conflict” preemption. Field preemption occurs where Congress, by statute, has clearly indicated an intent to occupy a certain field of regulation.6 Conflict preemption, on the other hand, occurs where compliance with both the federal and state law is impossible7 or the state law stands as an obstacle to the fulfillment of Congress’ intent in passing the federal law8. As a general matter, courts are reluctant to find preemption of state law, seeking in the first instance to find ways in which the state and federal laws be harmonized.
Until the enactment of federal “right to try,” the conventional wisdom was that state “right to try” laws, if challenged on federal preemption grounds, would be unlikely to survive, because compliance with them side-steps FDA approval and would be at direct odds with the Food, Drug and Cosmetic Act’s requirement of FDA oversight for expanded access. But there have been no challenges to state “right to try” laws based on preemption — nor were any anticipated — simply because the pathway provided under such state laws was separate and distinct from the pathway available under the FDA’s expanded access program, and each pathway was elective. So the state “right to try” laws and their requirements seemed irrelevant to companies electing to accommodate access under the FDA’s expanded access program.9 Indeed, that was the case for most manufacturers, providers and institutions who continued to operate under FDA’s expanded access framework, even in states with “right to try” laws.
While the question of whether aspects of state “right to try” laws survive preemption by the FDA’s expanded access law has gone largely unaddressed,10 the passage of federal “right to try” is likely to bring this issue more squarely into focus given that the federal “right to try” law is arguably less in conflict with its state counterparts. The state laws could reasonably be found by a court to supplement and explicate the way in which this activity (the provision of investigational drugs outside of FDA’s purview) can occur in a given jurisdiction, rather than serving to frustrate Congress’ intent in making the “right to try” pathway available. The ironic result for those who advocated “right to try” as a means of simplifying and expediting access may be that stakeholders operating under the federal “right to try” framework may now have to navigate two layers of regulations – one federal and the other state – with the latter consisting of a national patchwork of state-by-state variations.
How State “Right to Try” Laws May Still Supplement Federal “Right to Try”
In looking at how the state and federal frameworks interact, one might reasonably pose a threshold question: Can opting into the federal “right to try” pathway mean opting out of a state “right to try” pathway and render a state’s requirements irrelevant? Answering this question in the affirmative is unlikely to carry the day with regulators or courts, who could reasonably focus on the fact that the activity being carried out under federal “right to try” – that is, providing patients with access to unapproved drugs without FDA oversight – constitutes the very activity the state intends to regulate under its “right to try” law. Thus, even though manufacturers are not required by any of the state “right to try” laws to make their investigational products available for treatment purposes, if they choose to make them available under the federal “right to try” law in a state with “right to try” legislation, they are engaging in behavior for which the relevant state law establishes requirements. Also, given that the physicians and institutions who would be facilitating access to investigational drugs are licensed to operate by the state, few will care to risk disregarding any state law requirements other than those that are plainly preempted by the federal “right to try” law.
Proceeding, then, under the assumption that both the state and federal “right to try” laws may apply when a manufacturer engages in the regulated behavior of making investigational products available outside of FDA’s expanded access program, the question then becomes to what extent does the federal “right to try” law preempt state laws regulating the same activity? And, conversely, which aspects of state law are most likely to continue to apply? The federal “right to try” law does not expressly preempt state law. Returning then to the doctrines of implicit preemption, what aspects of state “right to try” laws, if any, are incompatible with federal “right to try” law such that complying with both is impossible or complying with state law frustrates the purposes and objectives of Congress?11
Aspects of State “Right to Try” Laws That Might Reasonably Be Deemed Compatible with Federal “Right to Try”
There are many ways in which the federal “right to try” law is consistent with common aspects of state “right to try” laws, such that compliance with both would seem entirely possible. As with federal “right to try,” all of the state “right to try” laws permit, but do not require, manufacturers of investigational drugs to make them available to certain eligible patients without FDA pre-approval. Also like the federal law, the state “right to try” laws generally require written informed consent. Both federal and most state laws require the investigational drug provided to have completed Phase I testing and to be under active study in an investigation overseen by the FDA.12
Furthermore, to the extent that federal and state “right to try” laws differ, many of the differences can co-exist, as they reflect more detailed statements under state law of the same principle contained in federal law. For example, several state laws outline explicit requirements for the content of written informed consent by the patient.13 These more specific requirements, as opposed to being inconsistent with the federal law, arguably could serve to further explicate the federal law’s requirement of written informed consent, which lacks further guidance as to content. Other state law provisions also arguably afford heightened protections to patients receiving investigational products without FDA oversight and, as such, could similarly be found by a court to survive preemption. For example, Arizona requires that a physician other than the treating provider be the one to request the investigational product. Several state laws require the determination of terminal illness to be confirmed by more than one physician. Texas prohibits charging for any costs, even the direct costs that the federal “right to try” law would permit. Manufacturers and providers facilitating access to investigational drugs will need to ensure that these additional protections discussed above, including the specific informed consent requirements, are met in addition to the federal law’s requirements, at least until a more definitive conclusion by a court in the relevant jurisdiction that the state requirements are preempted.
Several state laws also include provisions which, while arguably not in a patient’s interests, nonetheless likely survive. For example, Colorado and Connecticut grant insurers the right to deny coverage for the period the investigational product is taken plus a window of time following its administration. Given the primacy of states in regulating mandated insurance benefits, and the failure of the federal “right to try” law to address this issue, it is possible that a court would also find that these state law coverage provisions remain intact. Additionally, certain state “right to try” laws contain terms requiring that patients be notified, through the elements of written informed consent, that accepting investigational products under the state “right to try” law may trigger other state law consequences, such as eligibility for hospice benefits. As such, these terms do not create a new right to deny hospice benefits, per se, but are a notification of the fact that proceeding under “right to try” may result in ancillary unfavorable outcomes for the patient.14 Again, given the federal law’s silence on this topic, it is unlikely that a court would conclude that this interpretation of a state’s hospice requirements, as reflected in the “right to try” law’s informed consent requirements, is preempted.
Aspects of State “Right to Try” Laws That Might Reasonably Be Deemed to Conflict with Federal “Right to Try”
Areas where the federal and certain state laws potentially conflict include, importantly, the qualifying criteria for eligible patients. For example, under Pennsylvania law, a patient must have a terminal illness and must not be treated as an inpatient in any hospital (a criterion in several other states), whereas patients qualify under the federal “right to try” law if they have a “life-threatening disease or condition,” a defined term that is arguably broader. Furthermore, the federal “right to try” law does not differentiate between inpatients and outpatients. Under federal law, a patient must be “unable to participate” in a clinical trial (without guidance as to what makes one “unable”), whereas states may define ability in terms of not only geographic access but also rejection of an application to participate. Given that the purpose of the federal law is to promote access, it is possible that the state law, if it narrowed access by its definition of eligibility, would be preempted. Additionally, whereas the federal law provides no liability in a cause of action against sponsors or manufacturers (regardless of negligence, reckless or willful misconduct, etc.), state laws such as Pennsylvania’s provide immunity only to the extent of compliance with the state law and the exercise of “reasonable care.”
What This Means for Stakeholders
As manufacturers, physicians, institutions and IRBs continue to evaluate their positions on the new federal “right to try” law, those operating in jurisdictions with state “right to try” laws must consider the impact of those laws as well. Although most of the state “right to try” laws were premised on the Goldwater Institute’s model legislation, each contains unique variations and provisions that will need to be considered carefully to determine which parts, if any, of the state law would supplement obligations for stakeholders proceeding under federal “right to try,” or even those proceeding under FDA’s expanded access program. Understanding the ways in which potentially applicable state laws overlay the obligations of each federal option may further help inform stakeholders as they develop their policy and approach to compassionate use more broadly.
1 According to recent reporting, several high profile manufacturers appear to be of the view that the FDA’s expanded access program works well and there is no need to move to treatment use of investigational drugs under the federal “right to try” law. See Cortez, M. (2018). Dying Patients Face Reality Check on Right to Try. [online] Bloomberg.com. Available at: https://www.bloomberg.com/news/articles/2018-06-08/dying-patients-seeking-drugs-face-reality-check-on-right-to-try [Accessed 10 Jun. 2018].
2 See FDA’s answer to question #26 in FDA’s Guidance Document “Expanded Access to Investigational Drugs for Treatment Use – Questions and Answers – Guidance for Industry,” Issued June 2016, Updated October 2017, https://www.fda.gov/downloads/drugs/guidances/ucm351261.pdf.
3 See 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.
4 U.S. Const. art. VI.
5 See Securities Indus. Ass’n v. Connolly, 883 F.2d 1114, 1117 (1st Cir. 1989).
6 See Freightliner Corp. v. Myrick, 514 U.S. 280, 287 (1995).
7 See Florida Lime & Avocado Growers, Inc. v. Paul, 373 U.S. 132, 142-43 (1963).
8 See Hines v. Davidowitz, 312 U.S. 52, 67 (1941).
9 Indeed, there appears to have been only one publicly reported example of investigational drugs being made available through a state “right to try” law rather than through the FDA’s expanded access program). It involved a Dr. Ebrahim Delpassand, a Houston radiologist. After the FDA declined expansion of an expanded access treatment IND under which Dr. Delpassand was treating patients with an experimental radioisotope therapy, he proceeded under Texas’ “right to try” law instead. (From available reporting, it does not appear that the FDA has taken any action against Dr. Delpassand for treating under the state law without FDA approval.)
10 A follow-up lingering question (one that has not, to our knowledge, been directly tested either) is: assuming the state “right to try” laws are not completely preempted by the FDA’s expanded access program, which aspects of these state laws might survive and attach to the provision of investigational drugs for treatment even when done in accordance with FDA regulations?
11 As noted, field preemption could also form the basis for a court to conclude that the state laws are now invalid in the wake of the federal “right to try” law; however, given this is a more extreme result, and in the absence of a court decision directly on point, we have limited our analysis to conflict preemption.
12 Oregon requires that the investigational drug have successfully completed Phase I and be in Phase II-approved clinical trials.
13 These requirements may include for example: an explanation of the currently approved products and treatments for the disease or condition from which the patient suffers, an attestation that the patient concurs with his or her Physician in believing that all currently approved and conventionally recognized treatments are unlikely to prolong the patient’s life, a clear identification of the specific proposed investigational drug, and a description of the potentially best and worst outcomes of using the investigational drug.
14 Notably, to the extent this is based on an interpretation of a state’s eligibility criteria for hospice or other benefits, a similar outcome could theoretically be possible for patients receiving treatment using investigational products through FDA’s expanded access program.