Chapter 11 230 REGULATORY AND ETHICAL ASPECTS The United States: treatment or research? Despite the frequent use of evidence from expanded access programs, opinions differ on the extent to which data can be collected in this setting and in what way such data should be relied on. Expanded access pathways were first formalized by the US FDA in 1987.1 The focus was primarily on providing treatment: in a meeting on January 14th, 1993, the National Institutes of Health discussed the ‘research’ status of patients in US compassionate use programs for gene therapies.12 An FDA staff member noted that: ‘The Office for Protection from Research Risk maintains that such patients cannot be considered research subjects. An investigator who receives a single patient compassionate use exemption cannot include the results of that patient data in any further reports of their research.’ However, the current US legislation does not imply such a strict dichotomy between ‘research’ and ‘treatment’– there even is no clarity to whether participants in expanded access programs should be considered patients or research subjects. In the US, the expanded access program occurs under an ‘investigational new drug application’ and the dispensing physician is considered an ‘investigator’.5 The main intent of expanded access programs — to provide treatment — is thus in tension with this regulatory framework, which generally views the purpose of an investigational new drug application to be the conduct of clinical trials, for which the primary intent is evidence generation. Over the years, expanded access has been increasingly viewed as an alternate means of collecting information on harms and benefits. In a 2020 conference, the FDA’s principal deputy commissioner Janet Woodcock explicitly confirmed the agency’s view: ‘greater acceptance of data from (expanded access) treatment use to enhance generalizability in clinical development.’37 Although the views stated above are 27 years apart, there still is no consensus among regulators, bio-ethicists and drug developers on the ability to collect and analyze data from compassionate use.38–42 The European Union’s perspective In the EU, individual member states regulate expanded access programs. Although the EMA governs marketing authorizations via a centralized procedure, the EMA has no formal authority over expanded access requests and plays only an advisory role. The regulatory reluctance to rely on data from expanded access programs stems from concern over data quality. In the Guideline on Compassionate Use of Medicinal Products from 2007, the EMA has dedicated a section titled 5 21 C.F.R. § 312.305
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