Results from expanded access programs: a review of academic literature 129 7♦ Subsequently, we analyzed the full text articles for pre-defined main outcomes: time of publication, research location (country, national/international, single-center/multi-center), number of patients, research methodology (retrospective/prospective), drug, disease, and disease area. To provide the reader with insights that cannot be generalized across disease areas, and since expanded access gained particular attention during the COVID-19 pandemic, we specifically provide more detailed information on all COVID-19 related expanded access articles, including systematic analysis of all end points used (see Supplementary Material). Our screening procedure was tested on 50 abstracts prior to the start of the review. The detailed protocol is provided in the Supplementary Material. To give the reader more insight into the content of expanded access publications, we describe ten randomly selected articles in detail in the Supplementary Material. We cover the expanded access research setup, patient numbers, intervention, outcomes, and author interpretation of the results, including comparison with formal clinical trial results. Data management and statistics A chart was created in Excel 2010 (Microsoft, Redmond, WA) to tabulate the main outcome characteristics. We subsequently analyzed the data in R version 4.0.1 (PBC, Boston, MA), and code was generated to detect implausible values that were subsequently examined by the reviewers. The code to replicate this study is available on the GitHub of the first author.12 We used descriptive statistics to summarize our findings. To detect trends across time in the number of publications, we used a Spearman rank correlation test with a two-sided significance level of 0.05. RESULTS We examined 3,820 publications. After removing duplicates (n=10) and articles without full text (n=32), we screened 3,778 records for eligibility. We excluded articles not written in English (n=184) and not concerning expanded access (n=1,333). Finally, errata, replies, and editorials (n=101), news articles (n=50), or meta-analyses, systematic reviews, and guidelines (n=478) were removed. This led us to a collection of primary research on expanded access. We further removed non-pharmacological therapeutic articles, e.g., research on devices and procedures (n=133), and research on the legal, ethical, or policy aspects of expanded access (n=150). A schematic overview can be found in Figure 7. 12 https://github.com/TobiasPolak/
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