Prelude 10 INTRODUCTION To ensure patients and physicians have access to safe and effective drugs, regulators require the conduct of clinical trials to identify the risks and benefits of new treatments.1 The process of drug development requires effort and time, and as many as 15 years may pass to complete all phases of drug development.2 This encompasses preliminary pre-clinical research in petri dishes, followed by phase I trials involving healthy volunteers to evaluate safety and establish tolerable dosage levels. Next, in phase II, the investigational drug is tested on a larger group of patients with the targeted condition to determine its effectiveness, optimal dosage, and any further side effects. Finally, phase III trials test the drug on a large group of patients to compare the effectiveness and safety of the new drug or therapy with existing treatments or placebos. Despite remarkable advances in medicine for some disease areas, a substantial patient population remains without treatment options. Patients with mild, slowly progressing, non-lethal diseases may have the luxury of time at their disposal to await the outcomes of clinical trials to develop safe and effective medicine. Patients with life-threatening or seriously debilitating conditions cannot afford to await the results of regulatory evaluation and have sought access to investigational medicine through ‘expanded access’ pathways.3,4 The expanded access pathway provides a means to access investigational medicine when access through the preferred route - trial participation - is not possible. While patients may individually benefit from participating, clinical trials primarily generate knowledge for the collective advancement of medical science. However, a variety of barriers exist that impede patients from participating in trials, including ineligibility due to medical factors such as frailty, the presence of comorbidities, or the use of concomitant medications.5 Practical barriers, such as limited awareness of trials among patients and physicians, challenges with scheduling and travel to trial sites, or a complete lack of trials further hinder patient enrollment.6 Regrettably, research strongly suggests that sexist and racist factors worryingly hinder patient participation.7 When approved options are inadequate and trial participation is not feasible, patients in dire need may seek to access investigational drugs through legislated expanded access pathways. The history of expanded access The foundations of the expanded access pathway were laid in the United States (US).8,9 Prior to the 1980s, access to investigational drugs in the US was an informal process.10,11 The US Food and Drug Administration (FDA) permitted physicians to prescribe experimental treatments to severely ill patients on a case-by-case basis. The start of the AIDS crisis generated unprecedented attention to the regulatory process and sparked advocacy for broader access to treatments in research and increased patient involvement. Pressure from patient activists led the FDA to
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