Compassionate use, also known as expanded access, is a critical pathway for patients with life-threatening conditions to access investigational drugs when no other treatments are available. While this offers hope for patients, the process is fraught with challenges. The FDA’s latest guidance aims to clarify these complexities for Institutional Review Boards (IRBs) and clinical investigators1. This article will delve into the challenges that may have led to this guidance and offer recommendations for the clinical research community.

Challenges for Compassionate Use in Clinical Trials

Understanding the broader landscape of challenges surrounding compassionate use is essential. These challenges often serve as barriers for patients seeking access to investigational drugs and for clinical investigators and IRBs navigating a complex ethical regulatory and medical maze.

  • Streamlined Application Process: Despite the FDA’s efforts to streamline the expanded access program, public perception still views the FDA as an obstacle to accessing experimental therapies2. To elaborate, patients with terminal illnesses seeking compassionate use for unapproved therapies often encounter bureaucratic delays.
  • Ethical Question: Ethical dilemmas persist, such as who gets access to investigational drugs and how IRBs should review these cases3. The question of who gets access to a potentially life-saving drug can be heart-wrenching for patients suffering from terminal or life-threatening illnesses.
  • Rare Diseases: Finding patients and meeting the effectiveness criteria for rare diseases is challenging due to small patient populations and the potential for variability4. But when patients are disqualified for a study, sometimes compassionate use is their only option, especially for life-threatening genetic disorders. These patients require special care via a carefully crafted medical oversight plan.

FDA Guidance and Its Relevance to Compassionate Use Challenges

The FDA’s guidance responds to these challenges, offering a structured approach for IRBs and clinical investigators. It aims to align the ethical, procedural, and clinical considerations into a cohesive framework.

  • Types of Submissions: The guidance specifically targets individual patient expanded access submissions, aligning with the need for a streamlined application process.
  • IRB Procedures: The guidance recommends that IRBs establish procedures for single-member reviews, which could help navigate the ethical questions and challenges.
  • Risk and Benefit Assessment: The guidance emphasizes a thorough patient history and treatment plan, particularly important for rare diseases.
  • Informed Consent: The guidance stresses that the drug is investigational, aligning with the ethical considerations raised in the research.

Expanded Recommendations Based on FDA Guidance for Compassionate Use

For Investigators

  • Emergency and Non-Emergency Cases: The FDA guidance differentiates between emergency and non-emergency cases. Investigators should be prepared to follow specific protocols for each. For instance, emergency cases do not require prior IRB review but must be reported within five working days.
  • Patient History and Treatment Plan: The guidance emphasizes a thorough patient history and treatment plan review. Investigators should ensure that these documents are comprehensive and include criteria for discontinuation of treatment, planned dose modifications for adverse events, and planned monitoring for adverse events and response to treatment.
  • Pediatric Considerations: If the request is for a pediatric patient, investigators must ensure that provisions are made for age-appropriate assent from children and permission from a parent or guardian.

For IRBs

  • Waiver Procedures: The FDA intends to allow waivers for full IRB reviews under certain conditions. IRBs should establish clear procedures for when and how these waivers can be granted, ensuring that a designated IRB member concurs with the treatment before it begins.
  • Qualification Assessment: IRBs are advised to assess the qualifications of the physician submitting the individual patient expanded access request. This could include verifying credentials and assessing prior experience with the investigational drug or condition in question.
  • Informed Consent Requirements: The guidance specifies what should be included in the informed consent document. IRBs should ensure that the document meets these requirements, including a statement that the drug is investigational and has not been proven safe or effective for the treated condition.
  • Focus on Risk and Benefit: IRBs should focus their review on assessing the risks and benefits for the patient involved. This may require a more in-depth look at the patient’s history, including comorbid conditions and concomitant medications, to assess the potential for increased risks of the drug.

What This Means for the Patient

The FDA’s updated guidance aims to make it easier for patients to access experimental treatments when no other options are available. These guidelines focus on speeding up the application process, especially for those with rare or life-threatening conditions. They also address ethical questions about who gets access to these treatments, ensuring fair consideration for all. Additionally, patients and their families will receive detailed information to help them make informed decisions, and special provisions are in place for children and emergency situations. Overall, the new rules aim to make the system more transparent, fair and focused on the patient’s needs.


The FDA’s guidance on compassionate use and expanded access aims to streamline the process, clarify ethical dilemmas, and offer a structured approach for both investigators and IRBs. This is particularly significant for patients with life-threatening conditions who have exhausted all other treatment options. The guidance ensures that their cases will be reviewed with ethical considerations, provides a pathway for emergency access, and emphasizes the importance of informed consent and thorough patient history. This comprehensive approach aims to make the process more transparent, ethical, and patient-centric, ultimately benefiting patients in dire need.


  1. U.S. Food and Drug Administration. “Institutional Review Board (IRB) Review of Individual Patient Expanded Access Submissions for Investigational Drugs and Biological Products Guidance for IRBs and Clinical Investigators.” September 2023.
  2. Right now, in the right way: U. S. Food and Drug Administration’s expanded access program and patient rights
  3. Keeping a Focus on Research Ethics
  4. Challenges and opportunities when developing devices for rare disease populations
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Moe Alsumidaie Chief Editor
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.