A new ruling by the U.S. District Court for the Southern District of New York could require companies to make public a decade of clinical trial results for products that have been approved by FDA. Since 2016, HHS has taken the position that results of “Applicable Clinical Trials” of unapproved products completed between 2007 and 2017 did not have to be submitted to ClinicalTrials.gov, even if FDA later approved the products. But the District Court has now determined that HHS’ interpretation was unlawful.
Statutory and regulatory background
The Food and Drug Administration Amendments Act (FDAAA) of 2007 contained requirements for registering and submitting the results of Applicable Clinical Trials to ClinicalTrials.gov. (“Applicable Clinical Trials” is defined at 42 CFR 11.10(a)). In particular, FDAAA added a provision to the Public Health Service Act (PHSA) that required responsible parties to provide “Basic Results” for Applicable Clinical Trials of products approved by FDA. (42 USC 282(j)(3)(C)). These Basic Results include demographic and baseline characteristics of patients participating in the trial; the primary and secondary outcome measures of the trial; a table of values for each of the primary and secondary outcome measures for each arm of the clinical trial; a point of contact for scientific information about the clinical trial results; and whether there exists an agreement that restricts the ability of the principal investigator to discuss the results of the trial at a scientific meeting or any other public or private forum, or to publish in a scientific or academic journal information concerning the results of the trial.
In 2016, the U.S. Department of Health and Human Services (HHS) published a final rule titled “Clinical Trials Registration and Results Information Submission” (“Final Rule”), implementing the statutory provisions of FDAAA, with an effective date of January 18, 2017. Notably, in the preamble to the Final Rule, HHS declared that FDAAA’s requirement to post Basic Results of completed Applicable Clinical Trials would not apply if the product being studied was unapproved before the effective date of the Final Rule, even if FDA later approved the product. As HHS stated in the preamble to the Final Rule:
[W]hether results information submission is required for an Applicable Clinical Trial of an unapproved, unlicensed, or uncleared product depends on whether the primary completion date for that trial falls before or after the effective date of the regulations. If it falls before the effective date, then no results information is required to be submitted for that Applicable Clinical Trial, regardless of whether the product studied in that clinical trial is later approved, licensed, or cleared. (81 FR 64982, 65120, Sept. 21, 2016 (emphasis added)).
This interpretation by HHS is currently reflected on the ClinicalTrials.gov website:
For [Applicable Clinical Trials] that are required to be registered and with a Primary Completion Date before January 18, 2017 . . . If the [Applicable Clinical Trial] studies a drug, biological, or device product that is not approved, licensed, or cleared as of the Primary Completion Date, then the responsible party is not required to submit results information. (Frequently Asked Questions - ClinicalTrials.gov (Oct. 2019)).
The District Court’s decision
On cross-motions for summary judgment, the District Court ruled that HHS unlawfully interpreted FDAAA, and that the statute unambiguously required Basic Results to be submitted and posted for Applicable Clinical Trials of approved products, even if the products had not yet been approved prior to the effective date of the Final Rule. HHS expressed concern that if the District Court ruled that HHS’ interpretation of FDAAA was unlawful, then responsible parties would have to retroactively submit a decade of results for Applicable Clinical Trials of approved products. However, the District Court was unsympathetic to HHS’ concern, and countered that responsible parties had actually been on notice of the results posting requirement since FDAAA’s enactment in 2007:
[R]esponsible parties knew since the FDAAA’s enactment in 2007 that the statute required them to submit Basic Results for each [Applicable Clinical Trial] of a product that is approved. It was only when HHS promulgated the Final Rule nearly ten years after the FDAAA’s enactment and almost six years after the statutory deadline for doing so, and included in its preamble an interpretation of it that was contrary to the text of the FDAAA, that HHS definitively told responsible parties that they were not required to submit Basic Results for pre-Rule, pre-approval [Applicable Clinical Trials]. Defendants therefore created the retroactivity concern about which they complain.
Potential for appeal
The District Court’s decision set aside HHS’ interpretation “as contrary to the unambiguous terms of the FDAAA” and “enjoin[ed] defendants to comply with those terms.”
It remains to be seen whether HHS will seek to modify the District Court’s injunction and/or appeal the decision and seek a stay of the injunction pending appeal. If HHS does challenge the ruling, that process could take months or longer. If the District Court’s ruling is ultimately upheld, we expect that HHS will need some time to implement the ruling. We also expect that HHS would try to provide responsible parties a reasonable grace period to come into compliance.
Impact on life science companies and research institutions
If the District Court’s ruling is upheld on appeal – or if HHS decides to accept the court’s ruling – then responsible parties will be required to retroactively post the Basic Results of Applicable Clinical Trials of approved products completed between 2007 and 2017, even if the products had not yet been approved before the effective date of the ClinicalTrials.gov Final Rule.
To effectuate that, HHS would presumably need to amend the parts of the regulation that the court has invalidated. That would likely require publication in the Federal Register, but presumably would not require notice and comment rulemaking to effectuate. It will also depend on the amount of flexibility provided by the District Court in permitting the agency to come into compliance with its order. Once the new reporting obligations are formally in place, the pace of compliance with them may hinge on the extent to which FDA and NIH, Congress, or independent public watchdogs apply pressure to noncompliant institutions.
These reporting requirements would amount to another compliance obligation at a time when life sciences companies and research institutions – and particularly universities and academic medical centers – are facing myriad calls for transparency across their research enterprise.