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Exclusion rates in randomized controlled trials of treatments for physical conditions: a systematic review
Open accessAbstract
Background: The generalisability of randomized controlled trials (RCTs) can be uncertain because the impact of exclusion criteria is rarely quantified. The aim of this study was to systematically review studies examining the percentage of clinical populations with a physical health condition who would be excluded by RCTs of treatments for that condition. Methods: Medline and Embase were searched from inception to Feb 11th 2018. Two reviewers independently completed screening, full-text review, data extraction and risk-of-bias assessment. The primary outcome was the percentage of patients in the clinical population who would have been excluded from each examined trial. Subgroup analyses examined exclusion by population setting, publication date and funding source. Results: Titles/abstracts (20,754) were screened, and 50 studies were included which reported exclusion rates from 305 trials of treatments in 31 physical conditions. Estimated rates of exclusion from trials varied from 0% to 100%, and the median exclusion rate was 77.1% of patients (interquartile range 55.5% to 89.0% exclusion). Median exclusion rates for trials in common chronic conditions were high, including hypertension 83.0%, type 2 diabetes 81.7%, chronic obstructive pulmonary disease 84.3%, and asthma 96.0%. The most commonly applied exclusion criteria related to age, co-morbidity and co-prescribing, whereas more implicit criteria relating to life expectancy or functional status were not typically examined. There was no evidence that exclusion varied by the nature of the clinical population in which exclusion was evaluated or trial funding source. There was no statistically significant change in exclusion rates in more recent compared with older trials. Conclusions: The majority of trials of treatments for physical conditions examined excluded the majority of patients with the condition being treated. Almost a quarter of the trials studied excluded over 90% of patients, more than half of trials excluded at least three quarters of patients, and four out of five trials excluded at least half of patients. A limitation is that most studies applied only a subset of eligibility criteria, so exclusion rates are likely under-estimated. Exclusion from trials of older people and people with co-morbidity and co-prescribing is increasingly untenable given population aging and increasing multimorbidity. Trial registration: PROSPERO registration CRD42016042282 .
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Barnett, K., Mercer, S. W., Norbury, M., Watt, G., Wyke, S., & Guthrie, B. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60240-2 · Cited by 6,972
Self-citationAging with multimorbidity: A systematic review of the literature
Marengoni, A., Angleman, S., Melis, R., Mangialasche, F., Karp, A., Garmen, A., Meinow, B., & Fratiglioni, L. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2011.03.003 · Cited by 3,092
Boyd, C. M., Darer, J., Boult, C., Fried, L. P., Boult, L., & Wu, A. W. (2005) · JAMA · doi:10.1001/jama.294.6.716 · Cited by 2,581
External validity of randomised controlled trials: “To whom do the results of this trial apply?”
Rothwell, P. M. (2005) · The Lancet · doi:10.1016/s0140-6736(04)17670-8 · Cited by 2,544
GRADE guidelines: 8. Rating the quality of evidence—indirectness
Guyatt, G. H., Oxman, A. D., Kunz, R., Woodcock, J., Brozek, J., Helfand, M., Alonso-Coello, P., Falck-Ytter, Y., Jaeschke, R., Vist, G., et al. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2011.04.014 · Cited by 1,843
Spall, H. G. C. V., Toren, A., Kiss, A., & Fowler, R. (2007) · JAMA · doi:10.1001/jama.297.11.1233 · Cited by 1,054
Lee, P. Y. (2001) · JAMA · doi:10.1001/jama.286.6.708 · Cited by 841
The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995–2010
Guthrie, B., Makubate, B., Santiago, V. H., & Dreischulte, T. (2015) · BMC Medicine · doi:10.1186/s12916-015-0322-7 · Cited by 839
Self-citationSystematic Review of Barriers to the Recruitment of Older Patients With Cancer Onto Clinical Trials
Townsley, C. A., Selby, R., & Siu, L. L. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.00.141 · Cited by 587
Hughes, L. D., McMurdo, M. E. T., & Guthrie, B. (2013) · Age and Ageing · doi:10.1093/ageing/afs100 · Cited by 506
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Rothwell, P. M. (2006) · PLoS Clinical Trials · doi:10.1371/journal.pctr.0010009 · Cited by 399
Li, L., Geraghty, O. C., Mehta, Z., & Rothwell, P. M. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30770-5 · Cited by 393
Fortin, M. (2006) · The Annals of Family Medicine · doi:10.1370/afm.516 · Cited by 341
Masoudi, F. A., Havranek, E. P., Wolfe, P., Gross, C. P., Rathore, S. S., Steiner, J. F., Ordin, D. L., & Krumholz, H. M. (2003) · American Heart Journal · doi:10.1016/s0002-8703(03)00189-3 · Cited by 335
Adverse drug events in the outpatient setting: an 11‐year national analysis
Bourgeois, F. T., Shannon, M. W., Valim, C., & Mandl, K. D. (2010) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1984 · Cited by 333
Allocco, D. J., Cannon, L. A., Britt, A., Heil, J. E., Nersesov, A., Wehrenberg, S., Dawkins, K. D., & Kereiakes, D. J. (2010) · Trials · doi:10.1186/1745-6215-11-1 · Cited by 159
Exclusion of Older Adults from Ongoing Clinical Trials About Type 2 Diabetes Mellitus
Cruz-Jentoft, A. J., Carpena‐Ruiz, M., Montero‐Errasquín, B., Sánchez-Castellano, C., & Sánchez, E. (2013) · Journal of the American Geriatrics Society · doi:10.1111/jgs.12215 · Cited by 143
du Vaure, C. B., Dechartres, A., Battin, C., Ravaud, P., & Boutron, I. (2016) · BMJ Open · doi:10.1136/bmjopen-2016-012265 · Cited by 129
Saunders, C., Byrne, C. D., Guthrie, B., Lindsay, R. S., McKnight, J. A., Philip, S., Sattar, N. A., Walker, J. J., & Wild, S. H. (2012) · Diabetic Medicine · doi:10.1111/dme.12047 · Cited by 124
Self-citationBeaver, J. A., Ison, G., & Pazdur, R. M. (2017) · New England Journal of Medicine · doi:10.1056/nejmp1615879 · Cited by 97
Atkins, D. C., Chang, S., Gartlehner, G., Buckley, D., Whitlock, E. P., Berliner, E., & Matchar, D. B. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2010.11.021 · Cited by 95
Rengerink, K. O., Kalkman, S., Collier, S., Ciaglia, A., Worsley, S. D., Lightbourne, A., Eckert, L., Groenwold, R. H. H., Grobbee, D. E., & Irving, E. A. (2017) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2016.12.021 · Cited by 88
Thake, M., & Lowry, A. F. (2017) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2017.05.017 · Cited by 78
Characteristics of Randomized Controlled Trials Designed for Elderly: A Systematic Review
Broekhuizen, K., Pothof, A., de Craen, A. J. M., & Mooijaart, S. P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126709 · Cited by 68
Interpreting Treatment Effects From Clinical Trials in the Context of Real-World Risk Information
O’Hare, A. M., Hotchkiss, J. R., Tamura, M. K., Larson, E. B., Hemmelgarn, B. R., Batten, A., Do, T. P., & Covinsky, K. E. (2014) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.13328 · Cited by 67
Generalizability of Patients With Rheumatoid Arthritis in Biologic Agent Clinical Trials
Vashisht, P., Sayles, H., Cannella, A. C., Mikuls, T., & Michaud, K. (2016) · Arthritis care & research · doi:10.1002/acr.22860 · Cited by 57
Ahmad, N., Boutron, I., Dechartres, A., Durieux, P., & Ravaud, P. (2010) · Trials · doi:10.1186/1745-6215-11-20 · Cited by 53
The external validity of published randomized controlled trials in primary care
Jones, R., Jones, R. O., McCowan, C., Montgomery, A. A., & Fahey, T. P. (2009) · BMC Family Practice · doi:10.1186/1471-2296-10-5 · Cited by 42
Aaltonen, K., Ylikylä, S., Joensuu, J., Isomäki, P., Pirilä, L., Kauppi, M. J., Rannio, T., Eklund, K. K., Blom, M., & Nordström, D. (2016) · Lara D. Veeken · doi:10.1093/rheumatology/kew467 · Cited by 42
Justification of exclusion criteria was underreported in a review of cardiovascular trials
Schmidt, A. F., Groenwold, R. H. H., van Delden, J. J. M., van der Does, Y., Klungel, O. H., Roes, K. C. B., Hoes, A. W., & van der Graaf, R. (2014) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2013.12.005 · Cited by 41
Guthrie, B., Thompson, A., Dumbreck, S., Flynn, A., Alderson, P., Nairn, M., Treweek, S. P., & Payne, K. (2017) · Health Services and Delivery Research · doi:10.3310/hsdr05160 · Cited by 36
Self-citationMiró, Ò., Gil, V., Mueller, C. E., Mebazaa, A., Bueno, H., Martín‐Sánchez, F. J., Herrero, P., Jacob, J., & Llorens, P. (2015) · Clinical Research in Cardiology · doi:10.1007/s00392-015-0854-z · Cited by 29
Radner, H., Dixon, W. G., Hyrich, K. L., & Askling, J. (2015) · Arthritis Care & Research · doi:10.1002/acr.22602 · Cited by 25
Zhang, S., Liang, F., Li, W., & Tannock, I. F. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw129 · Cited by 20
Carey, M. P., Senn, T. E., Vanable, P. A., Coury-Doniger, P. A., & Urban, M. A. (2008) · Sexually Transmitted Diseases · doi:10.1097/olq.0b013e318148b4ba · Cited by 20
Halpina, D. M. (2010) · Primary Care Respiratory Journal · doi:10.4104/pcrj.2010.00015 · Cited by 17
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Guthrie, B., & Boyd, C. M. (2018) · Public Policy & Aging Report · doi:10.1093/ppar/pry038 · Cited by 17
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MethodResultTan, Y. Y., Papež, V., Chang, W. H., Mueller, S. H., Denaxas, S., & Lai, A. G. (2022) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(22)00186-6 · Cited by 284
Doody, P., Lord, J. M., Greig, C. A., & Phillips, A. C. (2022) · Gerontology · doi:10.1159/000528561 · Cited by 212
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Allison, R., Guraka, A., Shawa, I. T., Tripathi, G., Moritz, W., & Kermanizadeh, A. (2023) · Journal of Toxicology and Environmental Health, Part B · doi:10.1080/10937404.2023.2261848 · Cited by 167
Metadata
- Authors
- He, J., Morales, D. R., & Guthrie, B.
- Affiliations
- University of Dundee (GB)
- University of Edinburgh (GB)
- Corresponding author
- Guthrie, Bruce
- Venue
- Trials
- Published
- 2020-02-26
- Volume
- 21
- Issue
- 1
- Pages
- 228-228
- ISSN
- 1745-6215 (ISSN-L)
- PMC
- PMC7045589
- OpenAlex
- W3009768886
- Cited by
- 147
- References
- 37
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 34 · 2023: 31 · 2022: 20 · 2021: 13 · 2020: 4
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Trials (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Medical Research Scotland (Vac-965-2016)
- Health Services and Delivery Research Programme (NIHR HS&DR 11/2003/27)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Keywords
- exclusion rates, exclusion criteria, eligibility criteria, generalizability of trial results, physical health conditions, multimorbidity, older adults, co-prescribing, chronic disease, hypertension, type 2 diabetes, chronic obstructive pulmonary disease, asthma, trial funding, population aging
- MeSH terms
- Humans, Morbidity, Bias, Randomized Controlled Trials as Topic, Patient Selection
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