Avoiding Therapeutic Nihilism from Complex Geriatric Intervention “Negative” Trials: STRIDE Lessons

“I t ain’t so much what you don’t know that gets you into trouble, as what you know that ain’t so! ,” Will Rogers 1930s (? ) In the early days of the Journal of the American Geriatrics Society, the multifaceted complexity of aging was recognized in conjunction with a hypothesis that “relatively radical, vigorous, usually expensive, extensive therapeutic intervention may result in noteworthy rehabilitation of markedly debilitated aging and aged subjects. ” Two years later, Dr Joseph Sheldon observed that scant research existed around the problem of falls, simplistically attributed to just four causes. Fast-forward 65 years and falls remain a monumental problem for many older adults, linked to 32,000 deaths and 950,000 hospitalizations or transfers as over 27% of the U.S. population aged 65 years and older falls every year. A multistakeholder panel that included the American Geriatrics Society in 2010 provided clinical practice guidelines to evaluate fall risk and initiate efforts to reduce associated injuries. The U.S. Preventive Services Task Force (USPSTF) recently recommended select use of multifactorial interventions to reduce falls in at-risk community-dwelling older adults. Despite these recommendations, falls prevention efforts often seemed inadequate across healthcare settings, possibly attributable to an imperfect fit between research settings and real-world clinical care. The Patient-Centered Outcomes Research Institute and the National Institute on Aging funded the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) in 2014 to begin overcoming some of these practical barriers between research settings and everyday clinical practice in reducing fall morbidity via risk-assessment guided individualized care plans informed by the Chronic Care Model to balance evidentiary rigor with local adaptability. STRIDE included 86 primary care practices from 10 healthcare systems recruiting community-living, cognitively intact individuals 70 years or older (lowered from the original design ≥75 years due to recruitment issues) identified as increased risk for falls if they had experienced a fallrelated injury in the last year or had two or more falls in the prior year or were afraid of falling. Unfortunately, this well-funded, multicenter, pragmatic, cluster-randomized trial did not demonstrate a reduction in first serious fall injury. So how do clinicians, researchers, and guideline developers proceed without slipping into a counterproductive mindset of therapeutic nihilism in aging research? Although randomized controlled trials are perceived as the optimal method to understand the potential benefits or harms of an intervention by theoretically distributing confounders equally across treatment arms, their focus is on quantifying efficacy so research designs favor ideal conditions often inconsistent with actual clinical practice, which require effectiveness studies outside the research setting. Understanding effectiveness in real-world settings necessitates minimizing exclusion criteria and application of interventions by nonresearch personnel amidst the chaos of daily schedules, competing clinical priorities, nonadherent patients, and personal financial constraints. The reward for effectiveness research is a more confident understanding of external validity outside the ivory tower, whereas the disadvantage is lesser ability to understand whether the intervention might have worked in an ideal setting. Pragmatic trials ideally seek to enroll every eligible patient by waiving informed consent when possible, recruiting investigators across rural and nonacademic hospital settings, and delivering the intervention in normal practice using routine staff and equipment. In contrast to the simplistic views of 1955, falls often represent a complex web of aging physiology effecting gait, balance, sensory perception, cognition, and reflexes overlying medication adverse effects and home hazards. This underlies the USPSTF recommendation for individualized multifactorial interventions rather than far more simple interventions, such as eyeglasses or medication deprescribing. STRIDE is hardly the first complex intervention in geriatrics to render unexpectedly negative results (Table 1). In conjunction with STRIDE, these “negative” studies provide important lessons for future geriatric researchers testing solutions to complex health issues with multicomponent interventions.