Interpreting Treatment Effects From Clinical Trials in the Context of Real-World Risk Information

O’Hare, Ann M.; Hotchkiss, John R.; Tamura, Manjula Kurella; Larson, Eric B.; Hemmelgarn, Brenda R.; Batten, Adam; P., Thy; Covinsky, Kenneth E.

doi:10.1001/jamainternmed.2013.13328

Cited by 62 publications

(53 citation statements)

References 34 publications

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“…Indeed, renin-angiotensin system (RAS) inhibitors are undoubtedly the most effective therapies in nephrology to prevent ESRD. However, a recent simulation study with real-life data demonstrated that therapies with RAS inhibition would be considered totally ineffective if studies were performed in elderly patients with stage 3A CKD and no albuminuria (23). Our interpretation is that these elderly individuals with decreased GFR are actually not CKD patients.…”

mentioning

confidence: 76%

Lifetime Risk of CKD

Delanaye

Glassock

2015

Clinical Journal of the American Society of Nephrology

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confidence: 76%

Lifetime Risk of CKD

Delanaye

Glassock

2015

Clinical Journal of the American Society of Nephrology

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“…3 The rate of renal function loss over time is a predictor of mortality, and rapid loss correlates with an increased probability that dialysis will be required. There are few proven strategies to decrease renal disease progression.…”

Section: Managing Chronic Kidney Disease In Older Peoplementioning

confidence: 99%

“…These tools have not been designed to consider competitive risk of death and generally consider an eGFR of less than 15 mL/min/1.73 m 2 the point where a patient will require dialysis. 3 This eGFR cut point is inappropriate when considering the evidence that starting dialysis at eGFR levels greater than 10 mL/min/1.73 m 2 is not beneficial and may be harmful. 5 The most recent Canadian guideline for dialysis initiation considers the body of evidence and suggests "intent to defer" dialysis until an eGFR of less than 6 mL/min/1.73 m 2 is reached.…”

Section: Managing Chronic Kidney Disease In Older Peoplementioning

confidence: 99%

“…The Kidney Failure Risk Equation, initially developed in Canada, 3 predicts risk within 2 and 5 years for patients with an eGFR less than 60 mL/min/1.73 m 2 , using age, sex, current eGFR, and urine ACR. Sensitivity analyses using competing risk models did not reveal substantive differences in predictions.…”

Section: Managing Chronic Kidney Disease In Older Peoplementioning

confidence: 99%

“…Such persons uncommonly display signs of a progressive form of kidney disease, other than the usually slow, agerelated decline in eGFR (most commonly <1 mL/min/1.73 m 2 per year), 2 and seldom develop a requirement for treatment of end-stage renal disease, 3,4 thus rendering the "diagnosis" of CKD doubtful.…”

Section: Conflict Of Interest Disclosuresmentioning

confidence: 99%

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Managing Chronic Kidney Disease in Older People—Reply

Glassock

Delanaye

El‐Nahas

2016

JAMA

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In Reply Because our study was a phase 2B trial with the purpose of finding the optimal dosage with which to conduct a phase 3 outcome trial, strong conclusions should not be drawn from the results. Although Dr Feng and colleagues are correct that change in UACR at day 90 was the primary end point, we understand this is not consistent with any valid renal outcome and is a marker of inflammation and cardiovascular risk rather than renal injury. 1 We are fully aware of the variable relationship of high albuminuria and both kidney disease and cardiovascular outcomes from powered trials.We did not provide data on blood pressure variability because this was not a prespecified primary or secondary end point, although we are aware of the increased cardiovascular risk associated with increased blood pressure variability. We did perform ambulatory blood pressure monitoring in a subgroup of patients, and these data will be analyzed in the future.Hypotension was reported as an adverse event in less than 1% of patients; all events were of mild intensity, and none resulted in modification of drug therapy or any action with study drug.We appreciate the comment about dosing of ACE inhibitors and angiotensin receptor blockers contributing to greater effects on UACR; however, the study did not allow for titration of ACE inhibitors or angiotensin receptor blockers unless blood pressure was significantly elevated. In our trial, there was no significant uptitration of ACE inhibitors or angiotensin receptor blockers. Thus, the data are not confounded by increased dosing of other renin-angiotensin system-blocking therapies.We agree that outcome studies are needed and we have started studies involving 3 outcomes of diabetic kidney disease: kidney failure, cardiovascular outcomes, and heart failure. The first 2 trials are now recruiting patients and the heart failure trial will start within the next few months.

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Expanding Evidence for Clinical Care of Older Adults

Steinman

Boyd

Schmader

2021

JAMA

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For many years, clinicians who care for older adults have raised concern about the underrepresentation, and often exclusion, of older adults from clinical trials. However, in 2019, the National Institutes of Health (NIH) implemented a new requirement, the Inclusion Across the Lifespan policy, that all NIH-funded clinical trials must not set an upper age limit on eligibility unless there is strong scientific rationale to do so and must describe plans for enrolling individuals across the life span. 1 Moreover, the NIH has been at the forefront of efforts to ensure that trials not only enroll older adults but also do so in a manner that includes those from historically underserved groups and with multimorbidity, polypharmacy, frailty, and other geriatric conditions.These efforts are long overdue. Yet, as NIH and others have noted, simply enhancing the scope and diversity of older adult representation in traditional clinical trials will be insufficient to deliver the evidence needed to inform care for older adults. This Viewpoint highlights why complementary approaches, which often have received less attention, are necessary to achieve this goal.The problem arises from the tremendous heterogeneity in the health status of older adults. Overall fitness, burden of multimorbidity, cognitive and functional capacity, and life expectancy vary widely across this population. Moreover, these elements of health are

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Interpreting Treatment Effects From Clinical Trials in the Context of Real-World Risk Information

Cited by 62 publications

References 34 publications

Lifetime Risk of CKD

Lifetime Risk of CKD

Managing Chronic Kidney Disease in Older People—Reply

Expanding Evidence for Clinical Care of Older Adults

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