Observed and expected serious adverse event rates in randomised clinical trials for hypertension: an observational study comparing trials that do and do not focus on older people

Lloyd-Jones, 2005, Hypertension in adults across the age spectrum: current outcomes and control in the community, JAMA, 294, 466, 10.1001/jama.294.4.466 Russo, 2018, Impact of SPRINT results on hypertension guidelines: implications for “frail” elderly patients, J Hum Hypertens, 32, 633, 10.1038/s41371-018-0086-6 Lewington, 2002, Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies, Lancet, 360, 1903, 10.1016/S0140-6736(02)11911-8 Todd, 2019, Is the association between blood pressure and mortality in older adults different with frailty? A systematic review and meta-analysis, Age Ageing, 48, 627, 10.1093/ageing/afz072 Fortin, 2006, Randomized controlled trials: do they have external validity for patients with multiple comorbidities?, Ann Fam Med, 4, 104, 10.1370/afm.516 He, 2020, Exclusion rates in randomized controlled trials of treatments for physical conditions: a systematic review, Trials, 21, 228, 10.1186/s13063-020-4139-0 Ross, 1999, Barriers to participation in randomised controlled trials: a systematic review, J Clin Epidemiol, 52, 1143, 10.1016/S0895-4356(99)00141-9 Beckett, 2008, Treatment of hypertension in patients 80 years of age or older, N Engl J Med, 358, 1887, 10.1056/NEJMoa0801369 Wright, 2016, A randomized trial of intensive versus standard blood-pressure control, N Engl J Med, 374 Sheppard, 2020, Generalizability of blood pressure lowering trials to older patients: cross–sectional analysis, J Am Geriatr Soc, 68, 2508, 10.1111/jgs.16749 Luo, 2016, Population analysis of adverse events in different age groups using big clinical trials data, JMIR Med Inform, 4, e30, 10.2196/medinform.6437 Hanlon, 2019, Representation of people with comorbidity and multimorbidity in clinical trials of novel drug therapies: an individual-level participant data analysis, BMC Med, 17, 201, 10.1186/s12916-019-1427-1 Hanlon, 2020, Identifying frailty in trials: an analysis of individual participant data from trials of novel pharmacological interventions, BMC Med, 18, 309, 10.1186/s12916-020-01752-1 Fliser, 1993, Renal functional reserve in healthy elderly subjects, J Am Soc Nephrol, 3, 1371, 10.1681/ASN.V371371 Davies, 2015, Adverse drug reactions in special populations—the elderly, Br J Clin Pharmacol, 80, 796, 10.1111/bcp.12596 Wynne, 1989, The effect of age upon liver volume and apparent liver blood flow in healthy man, Hepatology, 9, 297, 10.1002/hep.1840090222 Van Spall, 2007, Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review, JAMA, 297, 1233, 10.1001/jama.297.11.1233 2012 Ioannidis, 2004, Better reporting of harms in randomized trials: an extension of the CONSORT statement, Ann Intern Med, 141, 781, 10.7326/0003-4819-141-10-200411160-00009 Konrat, 2012, Underrepresentation of elderly people in randomised controlled trials. The example of trials of 4 widely prescribed drugs, PLoS One, 7, 10.1371/journal.pone.0033559 Albasri, 2021, Association between antihypertensive treatment and adverse events: systematic review and meta-analysis, BMJ, 372, n189, 10.1136/bmj.n189 Mahr, 2017, Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials, Pharmacoepidemiol Drug Saf, 26, 731, 10.1002/pds.4169 Phillips, 2019, Analysis and reporting of adverse events in randomised controlled trials: a review, BMJ Open, 9, 10.1136/bmjopen-2018-024537 Farooqi, 2020, Accumulation of deficits as a key risk factor for cardiovascular morbidity and mortality: a pooled analysis of 154 000 individuals, J Am Heart Assoc, 9, 10.1161/JAHA.119.014686 Dahabreh, 2016, Using group data to treat individuals: understanding heterogeneous treatment effects in the age of precision medicine and patient-centred evidence, Int J Epidemiol, 45, 2184 Welch, 1996, Estimating treatment benefits for the elderly: the effect of competing risks, Ann Intern Med, 124, 577, 10.7326/0003-4819-124-6-199603150-00007 Thomopoulos, 2016, Effects of blood-pressure-lowering treatment in hypertension: 9. Discontinuations for adverse events attributed to different classes of antihypertensive drugs: meta-analyses of randomized trials, J Hypertens, 34, 1921, 10.1097/HJH.0000000000001052 Hanlon, 2006, Incidence and predictors of all and preventable adverse drug reactions in frail elderly persons after hospital stay, J Gerontol A Biol Sci Med Sci, 61, 511, 10.1093/gerona/61.5.511