{"doi":"10.1002/ana.25892","title":"The New Normal in Clinical Trials: Decentralized Studies","abstract":"As with health care delivery, coronavirus disease 2019 (COVID-19) has exposed weaknesses in clinical trials. Around the world, nearly all clinical studies were disrupted, many paused enrollment, and new trials were left on hold.1 Consequently, COVID-19 has postponed the promise of new therapies and cost the life sciences industry millions in additional costs and billions in foregone or delayed revenue. With guidance from the US Food and Drug Administration (FDA)2 and the European Medicines Agency (EMA),3 sponsors have adopted countermeasures to enable trial continuity during the current pandemic. These include in-home visits (eg, for laboratory tests and infusions), direct shipment of study materials to the participant's home, evaluations by video (eg, for rater-dependent outcomes), telephone calls (eg, for safety screening), online assessments (eg, for patient-reported outcomes), and remote patient monitoring. These measures and others mitigate the risk of skipped doses, missing data, and early study termination and have been adopted in clinical trials across disease areas, from cancer to stroke.1, 4, 5 Whereas helpful, these steps are merely temporizing. Current clinical trials have fundamental shortcomings. The cost to develop an approved therapy is between US $1 and 3 billion,6 the industry's productivity continues its decades-long decline,7 and trials only reach a small portion of interested participants.8 The COVID-19 pandemic presents an opportunity to re-envision clinical trials (Table 1), a change that is long overdue.1 Like the clinical care of patients, clinical trials should be designed around the needs and preferences of participants rather than sponsors or site. Technological innovations, such as the internet, social media, video conferencing, and smartphones, which have been long-used in other industries, allow such change. Various terms, including decentralized, direct-to-participant, and virtual studies, are used to describe such a concept.9 In general, all reflect the notion that (1) the focal point of all study activities is no longer the research site, (2) technology has enabled research to migrate toward participants, and (3) participants should have a greater voice in how and where research assessments are conducted.10, 11 These models are not new. Pfizer conducted the first randomized controlled trial of an investigational drug with no in-person site visits in 2011.12 The study used the internet for recruitment, online questionnaires for screening, electronic diaries for outcomes, and home delivery for distribution of the investigational drug. The FDA and public-private partnerships (eg, Clinical Trials Transformation Initiative) have supported or provided guidance on such studies.9 Like telemedicine for patient care, the time for these trials has arrived, and the novel coronavirus may be the forcing mechanism. Such studies offer numerous advantages over current site-based studies. First, because they are not tied to sites, they allow for a much broader pool of potential participants who can be recruited and screened online. Such screening, which can be aided by electronic health records and assess understanding of a study's aims,13 can be more efficient, safer, and ensure that only the most appropriate participants are referred for enrollment. Second, broader geographic participation allows for greater diversity in participation, improves the generalizability of results, and reduces recruitment time. Electronic consent is now increasingly available through multiple modalities (eg, online, telephone, and video) and part of many clinical studies.14, 15 Third, the potential for fewer research sites leads to fewer institutional review boards, reduced regulatory costs, lower training and monitoring expenses, and increased flexibility to make protocol changes. Fourth, a small number of investigators or a centralized group of raters can perform remote assessments leading to reduced variability and smaller stud","journal":"Annals of Neurology","year":2020,"id":55466,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":93,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":286687,"name":"Benzi M. Kluger","orcid":"0000-0002-6259-329X","position":1,"is_corresponding":false},{"id":286688,"name":"Craig Lipset","orcid":"0000-0002-7766-6340","position":2,"is_corresponding":false},{"id":110089,"name":"E. Ray Dorsey","orcid":"0000-0002-5140-1248","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-18T21:04:59.506324Z","pmid":"32869367","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}