Introduction

Compassionate use, also known as expanded access, refers to the provision of investigational medical products to patients with serious or life-threatening conditions when no satisfactory alternative therapies are available. This regulatory pathway allows patients to access drugs, biologics, or medical devices that have not yet been approved by regulatory agencies, such as the U.S. Food and Drug Administration (FDA), outside of clinical trials. Compassionate use is a critical intersection of medical ethics, regulatory oversight, and patient advocacy, particularly relevant in the context of rare diseases, pandemics, and rapidly evolving medical technologies.

Historical Context

The origins of compassionate use trace back to the HIV/AIDS crisis of the 1980s, when patient advocacy groups demanded access to experimental therapies. Regulatory authorities responded by creating formal mechanisms for expanded access. Over time, compassionate use policies have evolved to address emerging health threats and incorporate advances in medical science.

  • 1987: FDA establishes the Treatment IND (Investigational New Drug) program for AIDS patients.
  • 1997: The Food and Drug Modernization Act formalizes expanded access provisions.
  • 2018: The U.S. “Right to Try Act” provides an alternative pathway for patients to access investigational drugs without FDA oversight, under specific conditions.

Internationally, compassionate use programs exist in the European Union, Canada, Australia, and other regions, each with distinct regulatory frameworks and ethical considerations.

Main Concepts

1. Eligibility Criteria

Compassionate use is typically considered for patients who:

  • Have a serious or immediately life-threatening disease or condition.
  • Lack satisfactory approved therapeutic options.
  • Are unable to participate in ongoing clinical trials due to eligibility, location, or other factors.

2. Regulatory Oversight

Regulatory agencies set guidelines to balance patient safety with access:

  • FDA (United States): Requires submission of an expanded access IND application. Institutional Review Board (IRB) approval is mandatory.
  • EMA (European Union): National competent authorities oversee compassionate use programs; the EMA provides recommendations.
  • TGA (Australia): Special Access Scheme enables access to unapproved therapeutic goods.

3. Types of Compassionate Use

  • Individual Patient Access: For single patients, usually requested by a treating physician.
  • Intermediate-size Patient Populations: For groups not eligible for clinical trials.
  • Widespread Access Programs: For large populations, often during public health emergencies.

4. Ethical Considerations

Compassionate use raises complex ethical questions:

  • Patient Autonomy: Respecting patients’ rights to pursue experimental treatments.
  • Informed Consent: Ensuring patients understand potential risks and benefits.
  • Equity: Addressing disparities in access based on geography, socioeconomic status, or disease prevalence.
  • Data Collection: Balancing compassionate use with the need for robust clinical data.

5. Comparison with Another Field: Organ Transplantation

Both compassionate use and organ transplantation involve allocation of scarce medical resources under urgent circumstances. Key similarities and differences:

Aspect Compassionate Use Organ Transplantation
Resource Unapproved drugs/devices Donor organs
Regulatory Oversight FDA, EMA, national authorities UNOS, national transplant registries
Ethical Issues Access, consent, data collection Allocation, consent, equity
Impact on Clinical Research May affect trial enrollment Limited impact

Impact on Daily Life

Compassionate use directly affects patients with rare, advanced, or treatment-resistant diseases. Its broader impacts include:

  • Hope for Patients and Families: Provides options when conventional treatments fail.
  • Influence on Drug Development: Data from compassionate use can inform regulatory decisions and future research.
  • Healthcare Provider Responsibilities: Physicians must navigate complex regulatory and ethical landscapes to support patients.
  • Public Health Emergencies: During outbreaks (e.g., COVID-19), compassionate use programs expand access to investigational treatments, potentially saving lives.

Example: COVID-19 Pandemic

During the COVID-19 pandemic, compassionate use programs enabled access to remdesivir and monoclonal antibodies before formal approval. According to a study published in JAMA Network Open (2021), expanded access to remdesivir was associated with improved clinical outcomes in severely ill patients, highlighting the real-world impact of compassionate use pathways (Olender et al., 2021).

Recent Developments and Research

  • Digital Platforms: Recent advances include the use of digital health platforms to streamline compassionate use requests and data collection.
  • Global Harmonization: Efforts are underway to harmonize compassionate use policies across countries to facilitate multinational access.
  • Patient Advocacy: Advocacy organizations increasingly influence policy development, ensuring that patient voices are central to decision-making.

A 2022 review in Frontiers in Medicine emphasized the need for standardized reporting and outcome tracking in compassionate use cases, to maximize learning and minimize risks (Frontiers in Medicine, 2022).

Conclusion

Compassionate use is a vital mechanism for providing hope and potential benefit to patients facing life-threatening illnesses with limited treatment options. Its evolution reflects advances in medical science, regulatory policy, and patient advocacy. While compassionate use expands access, it also presents challenges in ensuring safety, ethical integrity, and equitable distribution. Ongoing research, policy harmonization, and technological innovation are essential to optimize compassionate use programs and their impact on patients and society.

Key Points for Revision

  • Compassionate use provides access to investigational treatments for patients with serious conditions lacking alternatives.
  • Originated during the HIV/AIDS crisis; now globally regulated.
  • Involves complex eligibility, regulatory, and ethical considerations.
  • Has parallels with organ transplantation in resource allocation and ethics.
  • Impacts patients, healthcare providers, drug development, and public health.
  • Recent studies and digital innovations are shaping future compassionate use practices.