Serious adverse events of older adults in nursing home and community intervention trials

Rupak Datta, Mark Trentalange, Peter H Van Ness, Joanne M McGloin, Jack M Guralnik, Michael E Miller, Michael P Walkup, Neelesh Nadkarni, Marco Pahor, Thomas M Gill, Vincent Quagliarello, Manisha Juthani-Mehta, LIFE Study Group, Rupak Datta, Mark Trentalange, Peter H Van Ness, Joanne M McGloin, Jack M Guralnik, Michael E Miller, Michael P Walkup, Neelesh Nadkarni, Marco Pahor, Thomas M Gill, Vincent Quagliarello, Manisha Juthani-Mehta, LIFE Study Group

Abstract

Background/aims: Clinical trials of older adults are increasingly common, but risks of serious adverse events (SAE) may vary. We describe the incidence of SAE in two randomized trials, one community-based and one nursing home-based.

Methods: We performed a secondary data analysis from two randomized clinical trials at one academic health center and 21 nursing homes involving 200 sedentary community dwellers aged 70-89 years and 185 female nursing home residents aged 65 years or older. Interventions included structured physical activity to reduce mobility disability in the Lifestyle Interventions and Independence for Elders (LIFE) study and oral cranberry capsules to reduce bacteriuria plus pyuria in nursing home residents (CRANNY) trial. We measured SAE incidence per 100 person-years and incidence of protocol-related unanticipated SAE per 100 person-years in LIFE and CRANNY trials.

Results: Mean age and proportion of patients with dementia in LIFE and CRANNY trials were 79.3 years and 86.4 years and 0% and 78%, respectively. There were 179 total SAE in LIFE including 8 (4%) deaths, and 116 total SAE in CRANNY including 33 (28%) deaths. SAE incidence was 33.7 (95% CI 27.2, 41.8) events per 100 person-years in LIFE and 69.4 (95% CI 49.1, 98.1) events per 100 person-years in CRANNY. No protocol-related unanticipated SAE occurred in either trial.

Conclusions: The frequency and severity of SAE vary in older adults. While SAE are common in nursing home residents, protocol-related, unanticipated SAE are rare in nursing home residents and community dwellers. This finding can inform trial monitoring protocols.

Trial registration: ClinicalTrials.gov identifiers: NCT01072500 and NCT01691430.

Keywords: Adverse events; Clinical trials; Older adults.

Figures

Fig. 1
Fig. 1
Adapted from current adverse event reporting guidelines under Department of Health and Human Services Code of Federal Regulations Title 45 Part 46.

References

    1. U.S. Department of Health & Human Services, Office for Human Research Protections . 2007. Unanticipated Problems Involving Risks & Adverse Events Guidance.
    1. National Institute on Aging . 2017. Data and Safety Monitoring.
    1. Kiel D.P., Magaziner J., Zimmerman S. Efficacy of a hip protector to prevent hip fracture in nursing home residents: the HIP PRO randomized controlled trial. J. Am. Med. Assoc. 2007;298:413–422.
    1. Fink H.A., Taylor B.C., Tacklind J.W. Treatment interventions in nursing home residents with urinary incontinence: a systematic review of randomized trials. Mayo Clin. Proc. 2008;83:1332–1343.
    1. De Deyn P.P., Katz I.R., Brodaty H. Management of agitation, aggression, and psychosis associated with dementia: a pooled analysis including three randomized, placebo-controlled double-blind trials in nursing home residents treated with risperidone. Clin. Neurol. Neurosurg. 2005;107:497–508.
    1. Pahor M., Guralnick J.M., Ambrosius W.T. Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE Study Randomized Clinical Trial. J. Am. Med. Assoc. 2014;311:2387–2396.
    1. Juthani-Mehta M., Van Ness P.H., Bianco L. Effect of cranberry capsules on bacteriuria plus pyuria among older women in nursing homes: a randomized clinical trial. J. Am. Med. Assoc. 2016;316:1879–1887.
    1. National Institute on Aging . 2017. Adverse Event and Serious Adverse Event Guidelines.
    1. Hanley J.A., Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. J. Am. Med. Assoc. 1989;249:1743–1745.
    1. Wallace S., Myles P.S., Zeps N. Serious adverse event monitoring in investigator-initiated clinical trials. Med. J. Aust. 2015;204:231–233.
    1. Rolland Y., Pillard F., Klapouszczak A. Exercise program for nursing home residents with Alzheimer's disease: a 1-year randomized controlled trial. J. Am. Geriatr. Soc. 2007;55:158–165.
    1. Mulrow C.D., Gerety M.B., Kanten D. A randomized trial of physical rehabilitation for very frail nursing home residents. J. Am. Med. Assoc. 1994;271:519–524.
    1. Broe K.E., Chen T.C., Weinberg J. A higher dose of vitamin D reduces the risk of falls in nursing home residents: a randomized, multiple dose study. J. Am. Geriatr. Soc. 2007;55:234–239.
    1. Riemersma-van der Lek R.F., Swaab D.F., Twisk J. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities. J. Am. Med. Assoc. 2008;299:2642–2655.
    1. Tariot P.N., Cummings J.L., Katz I.R. A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting. J. Am. Geriatr. Soc. 2001;49:1590–1599.
    1. Raskin J., Wiltse C.G., Siegal A. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial. Am. J. Psychiatr. 2007;164:900–909.
    1. Sivendran S., Latif A., McBride R.B. Adverse event reporting in cancer clinical trial publications. J. Clin. Oncol. 2014;32:83–89.
    1. Tang E., Ravaud P., Riveros C. Comparison of serious adverse events posted at and published in corresponding journal articles. BMC Med. 2015;13:189.
    1. Ionnidis J.A., Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. J. Am. Med. Assoc. 2001;285:437–443.
    1. Hartung D.M., Zarin D.A., Guise G.M. Reporting discrepancies between the results database and peer-reviewed publications. Ann. Intern. Med. 2014;160:477–483.
    1. Sivendran S., Galsky M.D. Adverse event reporting in oncology clinical trials – lost in translation? Expet Opin. Drug Saf. 2016;15:893–896.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir