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Invited Commentary |

The Gap Between Clinical Trials and the Real World Extrapolating Treatment Effects From Younger to Older Adults

Mary E. Tinetti, MD1,2
[+] Author Affiliations
1Section of Geriatrics, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
2Yale School of Public Health, New Haven, Connecticut
JAMA Intern Med. 2014;174(3):397-398. doi:10.1001/jamainternmed.2013.13283.
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The exclusion of older adults, particularly those with complex and multiple chronic conditions, from randomized clinical trials (RCTs) has been well chronicled.1,2 Less well studied is how the preventive benefits seen in participants in RCTs translate to older individuals with multiple chronic health problems.

Helping to fill this gap, O’Hare and coauthors3 investigate whether the benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in preventing progression to end-stage renal disease (ESRD) that are seen in younger populations would be similar for older adults. Using a simulation design, the authors provide evidence that the same relative benefit of ACEIs and ARBs seen in participants in RCTs do not provide the same absolute benefit in terms of less ESRD in older adults; this finding is important because the results from the participants in the RCTs inform current guidelines. For most of the older veterans in their study, more than 100 persons would need to be treated to prevent 1 case of ESRD. For many subgroups, the number needed to treat was greater than 1000, a sharp contrast to the range of 9 to 25 reported in the 4 trials highlighted in the article. These findings leave one wondering whether the poor translation of the effectiveness of ACEIs and ARBs from younger to older individuals is an isolated situation or whether we are unwittingly subjecting older adults to a wide array of preventive treatments that have no or marginal benefit or even impart unintended harm. The study by O’Hare et al supports the need to look at this question more systematically and calls into question the prevailing practice of assuming that results extrapolate from young to old and from healthier to sicker populations.

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