Review 32 http://infection.thelancet.com Vol 6 January 2006 Introduction HIV remains a threat to global health and economic stability. Approximately 3 million people succumbed to AIDS in the past year and a further 5 million were infected. 1 Shifts in the demographics of those infected have been marked by steadily increasing rates of infection among black people, heterosexuals, young people, and women; women now account for half of the world’s HIV/AIDS cases. 1 Although AIDS-associated deaths have decreased in regions where antiretroviral medicines are widely available, issues related to tolerance, viral drug resistance, long-term metabolic complications, and dosing schedules justify the need for continuing clinical research to identify effective and durable drug regimens. This clinical research is predicated on the ability to successfully enrol an adequate number of individuals in future antiretroviral studies. 2 Examination of the perceptions and attitudes of patients who are eligible for clinical trials is important for informing trial recruitment. Only qualitative studies that specifically inquire about barriers to trial participation can adequately inform us of important concerns for participants. However, many qualitative studies are done in specific settings or may have small sample sizes, so the findings from one study may not apply broadly to others. Systematic reviews of qualitative studies allow us to identify concerns that appear consistently in various settings. 3,4 We previously reported barriers to participating in HIV vaccine trials. 5 However, for HIV pharmacology trials, the limited body of research on recruitment issues 6 has largely focused on the under- representation of specific demographic populations including women, people of colour, and injecting drug users. 7 Few studies have examined specific barriers and anxieties that hinder an eligible individuals’ willingness to participate in HIV clinical trials. To better understand the obstacles to HIV clinical trial participation, we did a systematic review of the available qualitative and quantitative literature on this topic. Methods Search strategy We did a systematic, all-language literature search for all qualitative and quantitative studies that addressed the anxieties and barriers to HIV clinical trial participation. In duplicate, we searched the following databases: AMED (1985 to August, 2004), Campbell Collaboration (2001 to August, 2004), CINAHL (1982 to August, 2004), Cochrane Library (1998 to August, 2004), Embase (1990 to August, 2004), ERIC (1966 to August, 2004), Medline (1966 to August, 2004), and UK National Health Service Economic Evaluation Database (1975 to March, 2004). Unpublished studies were sought using the US National Library of Medicine’s ClinicalTrials.gov website (http://www.clinicaltrials.gov) and the UK National Research Register. Our search strategy combined terms that represented attitudes, barriers, and anxieties. Our search vocabulary included “HIV” or “AIDS”, “clinical trials”, “barriers”, “participat*” and “enrol*”. We supplemented this search by reviewing the bibliographies of key papers. Selection of abstracts Two members of the study team (BR and PW) independently reviewed the abstracts. Eligible studies met the following criteria: (1) reported an original research study; (2) contained content addressing barriers to participating in HIV clinical drug trials; and (3) were either a semi-structured interview, focus group study, or survey. We excluded studies that addressed only descriptions of participants or demographics, and vaccine trials. 5 Data abstraction and validity assessment Two reviewers (BR and PW) independently extracted data and appraised both validity and content. We characterised the content of the methods by use of a modified checklist designed to examine internal validity. 3,5,8 Qualitative studies were scored using this Lancet Infect Dis 2006; 6: 32–38 EM is Ontario HIV Treatment Network Fellow, LG is a statistician, and GG is professor of clinical epidemiology at the Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada; KW is associate professor of internal medicine at the Department of Medicine, University of Toronto, Toronto, Canada; BR is a graduate fellow at the BC Centre for Excellence in HIV/AIDS, Vancouver, Canada; PW is a graduate fellow at the London School of Hygiene and Tropical Medicine, London, UK; and CC is assistant professor of infectious disease at the Division of Infectious Diseases, University of Ottawa, Ottawa, Canada. Correspondence to: Dr Edward Mills, McMaster University, Faculty of Health Sciences, Clinical Epidemiology and Biostatistics, HSC-2C12, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. Tel +1 416 951 8530; fax +1 416 498 1643; millsej@mcmaster.ca Edward Mills, Kumanan Wilson, Beth Rachlis, Lauren Griffith, Ping Wu, Gordon Guyatt, Curtis Cooper The enrolling of adequate participants into HIV experimental drug trials presents an important challenge. We systematically reviewed the literature to identify barriers and concerns amongst HIV patients to participation in HIV clinical drug trials. We reviewed studies for validity and content, and generated pooled estimates of the frequency with which patients identified particular issues by pooling across studies that presented results as proportions. We included three semi-structured interview studies, two open-ended questionnaires, and nine quantitative studies. Major barriers to participation included fear of side-effects, distrust of researchers, general concerns about research design, interference in everyday life or changes in routine, and social discrimination. Results from the quantitative studies indicated that the most prevalent barriers were as follows: suspicions about the drug itself (53%, 95% CI 24–83%), patients were not informed or believed they were not eligible (38%, 25–50%), and travel or transport obstacles (39%, 21–57%). The findings of this study should aid drug trialists in developing strategies to maximise participation and cooperation in HIV clinical drug trials while adequately informing and protecting prospective participants. Barriers to participation in HIV drug trials: a systematic review