Discussion 259 patients enrolled in the program before trials were fully enrolled or completed, not only did it hinder trial enrollment, but the data generated from this program also suggested potential treatment benefits.37 However, subsequent randomized trials could not confirm that convalescent plasma improved outcomes for inpatient care.38 This program may not be a representative example of standard expanded access conduct, as the behavior in the face of a public health emergency like COVID-19 does not reflect day-to-day business, and the program was academia-driven instead of industry-led. Nonetheless, this serves as a cautious reminder that expanded access program and their data generation should be carefully defined and implemented prospectively while trials are already underway, and despite the size of the program, randomized trials remain unmatched in their ability to provide reliable estimates. Navigating the road ahead: realistic expectations Given the high stakes involved in the expanded access and regulatory approvals, it is irrefutable that actors will invariably try to circumvent regulations. For instance, patients may falsify their eligibility for inclusion in clinical trials or actively seek ways to do so, while companies may attempt to bend the rules to their advantage.39,40 These challenges are not inherent to expanded access, but rather stem from issues such as inadequate education, clouded moral judgments, or deliberate misconduct. Even though strong regulations and ethical oversight can reduce these occurrences, one should be careful not to base legislative judgement solely on rare exceptions. Expanded access is by no means a panacea, and it was never intended to resolve institutional issues in drug development.41 Marginalized groups’ inability to participate in trials,42 the potential exclusion of most patients due to stringent inclusion criteria,43 and the lack of randomized trials for drug approval are all problems not caused by expanded access and will not be solved through it.44 Efforts to include diverse populations should combat racism and sexism trial enrolment,45 pragmatic trials should include a wider variety of patients, and regulators should, where reasonable, enforce the conduct of randomized trials. Even with such improvements, some patients will miss out on trial participation.7 For these patients, expanded access still has a vital role to play – and evidence to generate. In an ideal scenario, this thesis would never have been written. In such a world, patients would have unfettered access to registered medicine that are proven to be safe and effective, or could seamlessly participate in randomized trials to evaluate risks and benefits to register novel medicines. However, this ideal remains elusive. Barriers that impede patient access to treatment will likely always exist, stemming from factors such as geography, regulations, gender, economics, race, timing, or simply due to a lack of luck. Access to medicine is not (yet) equitable. Although expanded access in a sense treats the symptoms rather than the disease, it can serve as a valuable
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