In a new Federal Register notice, the FDA announced that it will convene a public meeting on April 25 to hear patient perspectives and priorities on identifying and treating long Covid. While objective measures to diagnose the condition are lacking, the agency appears to be starting with patient-focused considerations for potential treatments.
Amid scientific and medical ambiguity, FDA seeks information from patients themselves regarding the long Covid lived experience
- Long Covid is defined as persistence of COVID-19 symptoms 4 weeks beyond SARS-CoV-2 infection, per the Federal Register meeting announcement. The condition is also sometimes referred to as post-Covid syndrome, post-acute sequalae of severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), long-haul Covid, or post-acute Covid-19 syndrome. The meeting announcement further describes a two-pronged system for classifying long Covid: subacute or ongoing Covid-19 symptoms (4-12 weeks of persistent symptoms post-infection) and chronic or post-Covid syndrome (12 weeks or more of persistent symptoms post-infection).
- Long Covid can present with a diverse array of physical and mental symptoms, many of which are debilitating but nonspecific, and may or may not align with symptoms of acute Covid-19 infection. While more than 200 symptoms of long Covid have been identified with impacts on multiple organ systems, the FDA identifies several “commonly reported” symptoms including “fatigue, brain fog, pain, palpitations, shortness of breath, cough, insomnia, anxiety, depression, constipation, and nausea.” According to the Centers for Disease Control and Prevention (CDC), this heterogeneity has made the prevalence of Long Covid challenging to assess, with estimates ranging from 5-30% of individuals who have had Covid-19.
- The underlying cause of Long Covid is unclear, and federal and international stakeholders are engaged in research to understand disease etiology and risk factors. According to a resource from the National Institutes of Health (NIH), researchers have hypothesized that long Covid symptoms could arise from factors such as reactivation of SARS-CoV-2 particles or overactive immune cells. In early 2021, NIH launched the Researching COVID to Enhance Recovery (RECOVER) Initiative to conduct clinical, observational, and pathobiological studies. In an April 2022 Presidential Memorandum, President Biden called for a “whole of government approach” that directed the Department of Health and Human Services (HHS) develop the interagency National Research Action Plan on Long Covid, issued in August 2022. The plan outlines research priorities and strategic government actions for long Covid research, while also acknowledging the challenges in measuring and researching a condition with no established definitions or biomarkers. Internationally, the World Health Organization (WHO) incorporated a new disease code for “post-COVID condition” into the International Classification of Diseases, Tenth Edition Clinical Modification (ICD-10-CM) as of October 1, 2021. WHO also created a global COVID-19 clinical platform case report form for clinicians and patients to compile standardized clinical data.
- Even without scientific consensus on long Covid, the agency is moving forward to collect patient input. The agency will host a Patient Focused Drug Development (PFDD) meeting on April 25 to hear patient priorities on the development of therapeutics for long Covid. Under the PFDD system, regulators and researchers engage a “systematic approach to help ensure that patients’ experiences, perspectives, needs and priorities are captured and meaningfully incorporated into drug development and evaluation.” PFDD approaches are intended to have several benefits, including better understanding what patients prioritize in their own treatments and improving trial or research participation experiences, as well as better understanding what risks and burdens the patients would be willing to accept – or what benefits they think are most impactful. This can be particularly helpful in areas of unmet need or where outcome measures can seem less straightforward, allowing developers to demonstrate that their treatments directly benefit living with the condition of interest.
- This is particularly relevant for patients with long Covid, especially as empiric evidence is still limited. At the meeting, the FDA intends to request feedback on three topics from patients (including both adults and pediatric populations): (1) health effects and daily impacts; (2) current approaches to treatment; and (3) clinical trial participation. For each topic, FDA plans to organize a patient panel, then facilitate a live discussion with both panelists and audience members. These insights will likely inform both regulatory and research priorities as industry and public health officials continue to work to better define long Covid. For developers interested in developing treatments for long Covid, the perspectives shared at the meeting will likely inform the types of outcomes or clinical outcome assessments (COAs) that they could capture in a research program – or that the FDA would want to see accounted for in a regulatory submission.
- Another key issue for Long Covid research: How to identify it? As CDC has noted, “there is no test that determines if your symptoms or condition is due to COVID-19,” and “post-COVID conditions are not one illness.” In order to develop a treatment for long Covid, diagnostic criteria will have to be developed. As AgencyIQ has previously discussed, diagnostic identification of long Covid using an FDA-approved (or cleared) product could potentially be a key consideration in coverage and reimbursement for long Covid services, thus bolstering market security for developers. At this point, though, there’s no clarity on how – or even whether – to test for long COVID. In late 2021, regulators from the FDA’s Office of In Vitro Diagnostics (OHT7) discussed the challenges of developing such a test, including “what the clinical usefulness” of a test would be. Research indicates that a one-size-fits-all diagnostic strategy is unlikely, given the wide variety of symptoms and organ systems involved. Other diagnostic tools under development include advanced methods to detect organ damage, such as microscopy to identify certain neuropathy and assessing certain abnormalities on electrocardiograms, as well as leveraging biomarker research from other conditions (including myalgic encephalomyelitis, formerly known as chronic fatigue syndrome) to try to identify a biomarker for long Covid.
- What’s next? The meeting will be held April 25, 2023, from 10 am – 4 pm ET. The meeting will also be accompanied by a docket for comments, open until June 26, 2023. As noted above, this meeting will be the first step in the FDA identifying priorities around – and then potentially guidance on – identifying a research population for long Covid studies and assessing what outcomes they would prioritize. Notably, POLITICO has reported that the newly sworn in 118th Congress may have limited interest in additional Covid-19 research funding bills, after $1.15 billion has already been specifically allocated to study long Covid. A lack of federal funding could limit the large-scale studies that will likely be needed to establish a population-level natural history understanding of the condition; as the POLITICO article notes, the RECOVER study will distribute funds “through the next two years,” according to NIH.
Includes prior research from Laura DiAngelo.
Key Documents and Dates
- Meeting: Patient-Focused Drug Development for Long COVID
- Meeting: April 25, 2023