Introduction

Compassionate use, also known as expanded access, refers to the provision of investigational medical products—such as drugs, biologics, or medical devices—to patients with serious or life-threatening conditions who have exhausted approved treatment options and cannot participate in clinical trials. This pathway allows patients early access to potentially life-saving therapies while regulatory review and clinical testing are ongoing. Compassionate use is governed by strict ethical, legal, and medical guidelines to balance patient safety with the urgent need for treatment.

Main Concepts

1. Definition and Scope

  • Compassionate Use/Expanded Access: The use of an unapproved medical product outside of clinical trials for patients with no other treatment alternatives.
  • Investigational Products: Drugs, biologics, or devices not yet approved by regulatory authorities (e.g., FDA, EMA).
  • Eligibility: Typically for patients with serious, life-threatening, or rare diseases who are ineligible for clinical trials.

2. Regulatory Framework

United States (FDA)

  • Expanded Access Programs (EAPs): The FDA outlines three pathways:
    • Individual Patient Access: For single patients, including emergency use.
    • Intermediate-Size Population Access: For groups of patients with similar conditions.
    • Treatment IND/Protocol: For widespread use during late-stage clinical development.
  • Requirements:
    • Serious or immediately life-threatening disease.
    • No comparable or satisfactory alternative therapy.
    • Benefit-risk assessment justifies use.
    • Inability to enroll in a clinical trial.
    • Manufacturer agreement to provide the product.
    • Institutional Review Board (IRB) approval.

Europe (EMA)

  • Compassionate Use Programs: Managed at the national level within EU member states, guided by EMA recommendations.
  • Criteria: Similar to the US, focusing on unmet medical need and patient safety.

3. Ethical Considerations

  • Informed Consent: Patients must be fully informed about risks, benefits, and alternatives.
  • Equity of Access: Ensuring fair and unbiased access regardless of socioeconomic status.
  • Balancing Risks and Benefits: Weighing the potential for harm against the lack of alternatives.
  • Impact on Clinical Trials: Concerns about undermining trial enrollment and data integrity.

4. Application Process

  • Physician-Initiated: Physicians submit requests on behalf of patients.
  • Manufacturer Role: Companies must agree to supply the investigational product.
  • Regulatory Review: Authorities assess eligibility, safety data, and manufacturing quality.
  • Ongoing Monitoring: Adverse events must be reported and tracked.

5. Examples in Practice

  • Oncology: Compassionate use is common for experimental cancer therapies.
  • Rare Diseases: Patients with rare genetic disorders often rely on expanded access.
  • Pandemics: During COVID-19, compassionate use was granted for therapies like remdesivir before full approval (Beigel et al., 2020, NEJM).

6. Recent Developments

  • Real-World Evidence: Data from compassionate use programs increasingly inform regulatory decisions.
  • Right to Try Laws: Some countries, including the US, have enacted laws allowing patients to bypass certain regulatory steps under specific conditions.
  • Digital Platforms: New technologies streamline application and monitoring processes.

Future Directions

  • Integration with Clinical Research: Enhanced data collection from compassionate use to support drug development and approval.
  • Global Harmonization: Efforts to standardize compassionate use policies across countries for consistency and efficiency.
  • Patient Advocacy: Greater involvement of patient organizations in policy development and access decisions.
  • Ethical AI Tools: Use of artificial intelligence to identify eligible patients and predict outcomes, improving safety and fairness.
  • Transparency Initiatives: Public registries and reporting to ensure accountability and inform future practice.

Impact on Daily Life

Compassionate use programs can offer hope to patients and families facing dire prognoses, providing access to cutting-edge therapies before they are widely available. For healthcare professionals, compassionate use requires balancing empathy with responsibility, ensuring patients are protected while pursuing innovative treatments. On a societal level, these programs highlight the importance of medical innovation, patient advocacy, and regulatory oversight in advancing public health.

Quiz Section

  1. What is the primary purpose of compassionate use programs?
  2. List three eligibility criteria for compassionate use in the United States.
  3. How does compassionate use differ from participation in a clinical trial?
  4. Name one ethical concern associated with compassionate use.
  5. How did the COVID-19 pandemic highlight the role of compassionate use?
  6. What is the role of the manufacturer in compassionate use programs?
  7. Describe one future direction for compassionate use policy.

Recent Research and References

  • Beigel, J.H., Tomashek, K.M., Dodd, L.E., et al. (2020). Remdesivir for the Treatment of Covid-19 — Final Report. New England Journal of Medicine, 383(19), 1813–1826. Link
  • U.S. Food and Drug Administration. (2023). Expanded Access (Compassionate Use). Link
  • European Medicines Agency. (2022). Compassionate use. Link

Conclusion

Compassionate use provides a critical safety net for patients with life-threatening conditions who have exhausted all approved treatment options. While offering hope, it also raises complex ethical, regulatory, and practical challenges. Ongoing improvements in policy, technology, and data integration aim to increase access while maintaining patient safety and the integrity of medical research. Compassionate use remains a vital aspect of modern healthcare, reflecting society’s commitment to compassion, innovation, and ethical responsibility.