FDA’s Role in Reviewing Research Proposals for Patient Safety
FDA has a critical role in ensuring the safety of patients in clinical trials studying drugs or biological products for the prevention or treatment of COVID-19 that require an investigational new drug (IND) application.
Many sponsors are providing clinical trial proposals to FDA for COVID-19 therapies before submitting an IND application. FDA has evaluated and responded to hundreds of these study proposals and questions from sponsors through this process. More information is available on the Coronavirus Treatment Acceleration Program (CTAP) webpage. As part of its review, FDA identifies any safety concerns that the sponsor must adequately address in the IND application before proceeding with a clinical trial.
Once a sponsor submits an IND application, FDA may determine that sufficient information has been provided to allow the trial to proceed (issuing a “Safe to Proceed” letter), or, if there is insufficient support to assure patient safety, or if there are safety concerns, FDA can issue a “clinical hold” to prevent a proposed trial from starting. This is to assure that subjects are not exposed to an unreasonable and significant risk of illness or injury. More information is available on CDER’s IND Application Procedures: Clinical Hold webpage. FDA has evaluated numerous IND applications for COVID-19 therapies and in some cases, due to patient safety concerns, issued a clinical hold to prevent a trial from proceeding.
FDA has been careful to assess whether proposed COVID-19 therapies in research proposals have potential safety concerns that might exacerbate the most serious and life-threatening symptoms of COVID-19 patients, such as respiratory adverse effects or pro-inflammatory immune response.
Examples of Patient Safety Concerns
Some examples of safety concerns identified by FDA in COVID-19 therapy proposals include:
- For a new drug or biological product, data from animal studies failed to support the safety of the product’s anticipated exposure (dose, route of administration, and duration) in humans for the proposed clinical trial
- For example, serious pre-clinical safety signals of a drug’s toxic effect were found in animal studies at a level that patients in the trial might be exposed to.
- For drugs or biological products already marketed for different indications, previously observed or anticipated toxicities of the product were not adequately addressed by the proposed safety assessments in a clinical protocol
- These safety concerns included therapies that can amplify cytokine release syndrome (a severe inflammatory response in the body that can lead to respiratory failure, organ failure and death) in a disease where patients were already at increased risk of this serious complication.
- For a new drug or biological product, insufficient information was provided about the product’s characteristics or how it is manufactured to allow FDA to assess the risks to subjects of the proposed study
Types of Research Proposals Not Allowed to Proceed
Some of the proposals that FDA has not allowed to proceed because of a lack of any plausible scientific basis for use in preventing or treating COVID-19 virus or symptoms, and which may expose the patient to significant known risks of the drug include proposed interventions with:
- Known toxic substances
- Botanical substances (e.g., plant materials, algae, mushrooms)
- Drugs or biological products approved for other indications without any plausible scientific basis for use in preventing or treating the virus or COVID-19 virus or symptoms, and which may expose the patient to significant known risks of the drug