Critical Extrapolation of Guidelines and Study Results: Risk-Benefit Assessment for Patients with Reduced Life Expectancy and a New Classification of Drugs According to Their Fitness for the Aged

Abstract

It is hard to understand that the largest group of drug consumers—elderly patients—is underrepresented in clinical trials. To avoid unclear results from patients with multimorbidity, elderly patients aged 65 or more years are almost routinely excluded from clinical trials. They obscure effect detection by events from concomitant diseases not addressed by the drug intervention, thereby diluting the “true” events under question. Only very recently, few exceptions from this rule have surfaced, with a study on arterial hypertension in the very elderly and several studies on new anticoagulants in the treatment of atrial fibrillation as signs of hope. In addition, regulatory authorities increasingly demand studies on pharmacokinetics in the elderly, although such studies are generally small and not powered to detect endpoint effects or assess safety in the elderly. Still, in the typical case of a newly developed drug, its clinical development was mainly restricted to younger adults, but it will be used predominantly in the group of elderly patients in whom it had never or only insufficiently been tested. This points to a large evidence gap in this context; as evidence-based medicine (EBM, defined by Sackett; Sackett et al. 2007) critically depends on evidence and guidelines almost automatically claim evidence as their major source of reasoning, we witness the critical absence of genuinely EBM-based guidelines for the elderly (Wehling 2011). For example, in the 2007 European guideline on arterial hypertension (Mancia et al. 2007), less than one page is devoted to treatment of the elderly although arterial hypertension represents one of the few therapeutic areas for which data in the elderly are emerging (see section “Positive Assessment of Drugs for the Elderly”). In the reappraisal of the guideline in 2009 (Mancia et al. 2009), also one page seemed sufficient for this. In the U.S. JNC 7 guideline (Chobanian et al. 2003), hypertension in the elderly is presented on less than two pages. But, there is hope: Recently the first consensus statement on the treatment of hypertension in the elderly (Aronow et al. 2011) extensively and comprehensively described all major aspects of hypertension treatment in the elderly on 81 pages.