The Key Differences Between Expanded Access Programs And Investigator Sponsored Trials
By Christopher Ohms, Ohms Consulting
In the realm of medical research and access to experimental treatments, expanded access programs (EAPs) and investigator sponsored trials (ISTs) play significant roles. While both aim to provide patients with access to investigational therapies, they operate under distinct frameworks and serve different purposes. Understanding their differences from traditional clinical trials (e.g., Phase 1, 2, 3, etc.) is crucial from an investigational medicine product (IMP) and supply chain perspective.
Expanded Access Programs
EAPs, also known as compassionate use programs, are designed to provide patients with serious or life-threatening conditions access to investigational drugs outside of clinical trials when no satisfactory alternatives are available. For instance, consider a patient diagnosed with an aggressive form of cancer for which standard treatments have failed. Having joined a Phase 2 clinical trial, upon its conclusion, the attending physician can initiate a request for the patient to participate in an EAP, ensuring ongoing access to the experimental medication beyond the trial's end.
Additionally, patients who do not meet the inclusion criteria for ongoing clinical trials but have a critical need for the investigational drug may qualify for EAP. For example, imagine a child suffering from a rare genetic disorder with no approved treatment options. While the child does not meet the age criteria for inclusion in a Phase 3 trial, the severity of their condition prompts the physician to seek access to the investigational drug through an EAP.
While EAPs offer a route for early access to experimental treatments or those not yet approved for that intended indication, they still operate within regulatory frameworks to ensure patient safety and monitor treatment outcomes. EAP protocols must be reviewed and approved, detailing the criteria for patient selection, treatment protocols, and safety monitoring. EAPs are often limited in scope and duration. They are not intended to substitute for traditional clinical trials but rather to provide access to treatments for patients where the trial has ended or for patients who cannot participate in trials due to eligibility criteria or logistical constraints.
Regulatory bodies such as the U.S. FDA and the European Medicines Agency (EMA) govern EAPs to ensure that patients receive investigational treatments safely and ethically. In the United States, the FDA allows patients with serious or life-threatening conditions to access investigational drugs through expanded access programs. The FDA provides guidance and regulations outlining the procedures for physicians, patients, and pharmaceutical companies to follow when seeking access to investigational drugs outside of clinical trials. These regulations aim to balance patient autonomy and safety while facilitating access to promising therapies. The Federal Investigational Drug Caution Statement, as outlined in CFR 21 Part 312.6, stipulates that the label of an investigational new drug intended for human use should include the statement "Caution: New Drug—Limited by Federal (or United States) law to investigational use." This cautionary statement serves to inform users about the investigational nature of the drug and its limitations.
Similarly, the EMA in Europe provides a framework for compassionate use programs to ensure that patients with unmet medical needs can access investigational drugs under controlled conditions. The EMA's guidelines outline the criteria for eligibility, the responsibilities of healthcare professionals, and the procedures for obtaining authorization to use investigational drugs outside of clinical trials. By adhering to these regulations, pharmaceutical companies can participate in EAPs while fulfilling their ethical and regulatory obligations. It is important to note not all European countries allow EAPs and some require specific oversight prior to initiation and throughout the duration of the treatment.
Investigator Sponsored Trials
In contrast to EAPs, ISTs are clinical studies initiated and conducted by independent researchers or institutions. Unlike EAPs, which primarily focus on providing access to investigational drugs, ISTs aim to generate data to support regulatory approval or expand knowledge about a particular treatment's efficacy and safety profile. For example, consider a researcher investigating the potential use of a repurposed drug in treating a rare autoimmune disorder. The researcher designs a trial protocol to evaluate the drug's effectiveness and safety in this patient population, with the goal of contributing to scientific understanding and potentially influencing future treatment guidelines.
To illustrate further, let's delve into a hypothetical scenario involving both EAPs and ISTs:
Imagine a pharmaceutical company developing a promising new therapy for Alzheimer's disease. During Phase 2 clinical trials, some patients demonstrate significant improvements in cognitive function and quality of life. However, due to limited resources and stringent inclusion criteria, not all patients with Alzheimer's can participate in the trial. Recognizing the urgent need for effective treatments in this population, the company decided to initiate an expanded access program for patients who did not meet the trial's criteria but could benefit from the investigational drug.
One such patient is Sarah, a 70-year-old woman diagnosed with early-stage Alzheimer's disease. Despite undergoing conventional treatments, Sarah's condition continues to worsen, affecting her memory, cognition, and ability to perform daily tasks. Her neurologist, Dr. Watson, is aware of the ongoing EAP and believes Sarah could benefit from the investigational drug based on her clinical presentation and medical history. Dr. Watson submits a request to enroll Sarah in the EAP, providing detailed documentation of her condition and rationale for seeking access to the investigational therapy.
Meanwhile, in a different part of the country, Dr. Crick, a neuroscientist at a prestigious research institution, is planning an investigator sponsored trial to further investigate the potential benefits of the same investigational drug in Alzheimer's patients. Dr. Crick's study aims to explore the drug's mechanisms of action, optimal dosage regimens, and long-term safety profile. By conducting a rigorous clinical trial with standardized protocols and endpoints, Dr. Crick hopes to generate robust data that can support future regulatory submissions and inform clinical practice guidelines.
EAP And IST Supply Chain Considerations
From a pharmaceutical supply chain perspective, ensuring the timely and efficient delivery of the investigational drug to both the EAP and IST sites is essential. The pharmaceutical company must establish close collaboration among its chemistry, manufacturing, and controls (CMC), quality assurance (QA), and supply chain teams to ensure the production, packaging, and labeling of IMPs align with regulatory requirements and meet the heightened demand arising from multiple EAPs and clinical trials concurrently. Furthermore, optimizing packaging and labeling logistics is crucial to facilitate the distribution of the investigational drug to various clinical sites while ensuring compliance with regulatory requirements, including the inclusion of the Federal Investigational Drug Caution Statement as outlined in CFR 21 Part 312.6.
In the case of the EAP, where patients may have varying treatment protocols and dosing regimens, having flexible labeling options allows healthcare providers to customize the IMP labels based on individual patient needs. This flexibility ensures that essential information such as proper identification, lot number, retest dating, and storage condition statements are included while allowing for protocol-specific details to be filled in as needed. By adhering to good manufacturing practices (GMPs) and regulatory guidelines, the pharmaceutical company can maintain consistency and quality in IMP labeling across different EAPs and ISTs.
Furthermore, effective inventory management and demand forecasting are essential to prevent stockouts and ensure a continuous supply of medication to enrolled patients. By leveraging forecasting efforts and real-time inventory tracking, the pharmaceutical company can anticipate demand fluctuations, optimize resource allocation, and minimize wastage. Collaborating closely with distribution partners and clinical sites allows for seamless coordination of supply chain activities and timely delivery of the investigational drug to patients in need.
In conclusion, EAPs and ISTs play vital roles in providing patients with access to investigational therapies and advancing medical research. From a pharmaceutical supply chain perspective, it is essential to navigate regulatory requirements, optimize labeling and packaging logistics, and ensure efficient inventory management to support these initiatives effectively while prioritizing patient safety and treatment access.
About The Author:
Christopher Ohms is a consultant at Ohms Consulting and is a San Francisco Bay Area native. He has held positions at Rigel Pharmaceuticals, Gilead Sciences, Patheon, Stanford School of Medicine, Pain Therapeutics, and ALZA.