The MAHA Assessment’s Implications: Drugs (Part One)

Among other things, EO 14212 established the Make America Healthy Again (MAHA) Commission (with HHS Secretary Kennedy as its Chair) and tasked it with a tall order: submission to the President of an Assessment that tackled 10(!) complex public health issues within 100(!) days. Perhaps it was inevitable that the Commission would turn to AI for help, as seems to have been the case in light of media reports that the Assessment as originally published included references that don’t exist. We lawyers have seen that show before.

The process through which the Assessment was developed remains a mystery. Ordinarily, a public health initiative of such magnitude would have been governed by a transparent multi-step process featuring public meetings and drawing on external scientific expertise. In this instance, the Assessment appears to have been developed behind closed doors, and evidently did not undergo an internal or external review thorough enough to capture these errors.

Nevertheless, pursuant to EO 14212, the Commission now has less than 80(!) days to submit to the President a Strategy based on the findings of the Assessment. The Strategy must “address appropriately restructuring the Federal Government’s response to the childhood chronic disease crisis, including by ending Federal practices that exacerbate the health crisis or unsuccessfully attempt to address it, and by adding powerful new solutions that will end childhood chronic disease.” In other words, as you read this, the Assessment’s findings and recommendations are getting baked into federal government policy, for better or worse.

What might that look like for the drug sector? As stated, the primary focus of the Assessment is on chronic diseases, encompassing both their causes and their treatments. The Assessment uses a significant amount of real estate to discuss prescribing practices, alleging that current practices amount to overprescribing. The Assessment highlights various trends related to chronic disease diagnoses (such as increasing rates of autism spectrum disorder and attention deficit hyperactivity disorder) with associated trends in prescribing practices.

This overprescribing relates to a lack of long-term data for either safety (particularly neurodevelopmental) and efficacy for drugs which are nevertheless often prescribed long-term. There are also drugs the Assessment identifies as being used off-label without high-quality evidence or for uses that are approved but without rigorous “true placebo”-controlled trials (namely vaccines) and/or with known safety concerns. Some specific examples cited in the Assessment are the increased use of stimulants to treat ADHD despite evidence they did not improve long-term outcomes, higher rates of antidepressant prescribing despite evidence that psychotherapy is as effective in the short-term and potentially more effective long-term, increased prescribing of antipsychotic medication with many prescribed for off-label conditions in children, and unnecessary antibiotic use that is associated with higher rates of certain chronic conditions. The Assessment states that this prescribing is tantamount to doing direct harm, given the known and unknown risks and benefits of drugs in these contexts of use.

This Assessment does not itself prescribe specific remedies for the ills it diagnoses; those are supposedly coming in the future Strategy document. That leaves us to speculate what the implications of this Assessment will be. Notably, many of the issues regarding drugs are typically considered the practice of medicine, which FDA does not regulate.

However, that does not mean FDA is has no tools to address what the Assessment refers to as the “Overmedicalization of Our Kids.” Therapies for chronic diseases, even in pediatrics, are not approved based on decades-long studies, and this is not likely to change. Indications for chronic diseases do not generally reflect the length of the clinical trial; FDA determines that clinical trials supporting such approvals are of sufficient duration and makes an approval determination. If there are no known or anticipated safety or efficacy concerns from continued use, FDA draft guidance states that the description of the duration of use from the clinical trials should be discussed in the Clinical Studies section of labeling, not in the Indications and Usage section, as it is generally not necessary to limit duration of use in the indication unless it is essential to ensure the safe and effective use of the drug. Likewise, contraindications describe situations in which the drug should not be used because the risk of use clearly outweighs any possible therapeutic benefit; however, this should include only known hazards, and not theoretical possibilities. The Assessment suggests that FDA may be viewing indication claims with greater scrutiny moving forward, either at the time of approval or after, when such information may be available.

Known clinically relevant safety and effectiveness information is generally included in the label under current practices. However, as the Assessment notes, “[t]here are…many possible adverse events for which there is inadequate evidence to accept or reject a causal relationship,” which may otherwise lead manufacturers to opt not to include them in the labeling. This Assessment suggests causation may be viewed using a different standard moving forward, leading to the inclusion of additional information in the Warnings and Precautions or Adverse Reactions sections of drug labeling, or other potential consequences.

FDA also has other tools, such as Risk Evaluation and Mitigation Strategies (REMS), which are implemented to ensure that the benefits of a drug outweigh the risks. However, the most burdensome REMS restrictions, Elements to Assure Safe Use, are intended for situations only where specific serious risks are identified.

Similarly, FDA can use post-marketing requirements (PMRs). PMRs are implemented to assess possible serious risks associated with drugs, which can include assessing known serious risks, assessing signals of serious risks, or identifying an unexpected serious risk when available data indicate the potential for a serious risk. This can resemble enhanced post-marketing surveillance, and it is not difficult to see how the MAHA Assessment may support an increase in their usage where the qualifying criteria are met.

The Assessment does not focus solely on safety. For example, it describes a “replication crisis,” which it suggests should be addressed by government agencies to confirm both safety and efficacy findings from industry-funded research. Such efforts are intended to “improve trust and reliability in basic science and interventions in childhood chronic disease” and may have implications for labeling or continued approvals.

As described here in brief, FDA has a variety of tools that are already in use to address the issues raised in the MAHA Assessment. For example, the Assessment notes that SSRIs carry a Boxed Warning describing the risk of suicidal thinking and behavior in adolescents to facilitate safe prescribing practices. However, if FDA determines that these tools are not sufficient to address the issues described in the Assessment, we may see their use enhanced. Ultimately, FDA has the authority to decide whether benefits of a drug outweigh the risks, either in only limited circumstances, only with appropriate warnings, or in no circumstances, and approvals may be limited or withdrawn. Approvals may also not be made at all or may require more evidence, as we may also see increased pre-approval requirements such as true placebo-controlled trial requirements for vaccines. We will continue to monitor these developments as they come.