Elderly people are now the most rapidly growing part of the patient population worldwide, thanks to more focus on primary prevention of diseases and improvements in healthcare for the younger ill patient. Aging is often accompanied by chronic (multiple) diseases, comorbidity, disability, frailty, and social isolation. As a consequence, elderly persons are more likely to receive a high number of drugs; this phenomenon is called “polypharmacy” and is a problem affecting advanced decades and may lead to an increased risk of inappropriate drug use, underuse of effective treatments, medication errors, poor adherence, drug–drug and drug–disease interactions, and, most importantly, adverse drug reactions [1]. Moreover, the lack of well-designed clinical studies recruiting elderly limits the availability of evidence-based information on the effect of drugs on clinically relevant outcomes such as functional and cognitive decline, quality of life, adverse events, and mortality. This is a real problem for the majority of chronic conditions, particularly for cardiac diseases, which are predominant in elderly persons.

In order to limit this problem, in 1989 the US Food and Drug Administration (FDA) published, referring to pharmaceutical industry, guidelines for studying the most used drugs in elderly [2]. These recommendations have been revised and strengthened in 1994, in a document compiled by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH; http://​www.​ich.​org), an organization that gathers drugs regulatory agencies of the United States (FDA), Europe (European Medicines Agency, EMA), and Japan, underlining the importance of including in randomized clinical trials (RCT) patients representative of the population in which the drug will be prescribed, in particular, including people over 75, without age limits and “unnecessary exclusion criteria for comorbidity” during recruitment [3].

Despite this, elderly are still usually excluded from RCT. A systematic review of RCT’s eligibility criteria in 2007 shows that comorbidities and predefined age limits were the main reasons for elderly exclusion [4]. Women, children, and elderly were the most frequently excluded categories in the majority of clinical studies [4].

The reasons for this attitude are quite easy to understand; in fact, the need of enrolling homogeneous study population, lowering the risk of dropout, and reducing compliance and pharmacological interactions are all important issues when designing a clinical trial.

There’s the perception that advanced age is a vulnerable condition per se and that enrolling elderly in RCTs could increase direct and indirect costs; moreover, the exclusion of this population from RCT is not perceived as a major problem, erroneously transferring results obtained in younger to older people individuals [5].

The European multicentric study PREDICT (Increasing the PaRticipation of the ElDerly In Clinical Trials), published in 2011 [6], involved eight European countries and Israel and was aimed to investigate attitudes in recruiting older persons in RCTs, in order to understand reasons of their systematic exclusion. The results of this project were not encouraging. In fact, despite the recommendations offered by the Helsinki Declaration of the World Medical Association and by several national and international regulatory agencies (e.g., US Food and Drug Administration, European Medicines Agency, and International Conference on Harmonization) and the best efforts of several opinion leaders in the field, the exclusion of older individuals in CTs continued to be widespread in pharmacologic and nonpharmacologic trials. This is particularly true for some chronic conditions, as for example, chronic heart failure [6].

Informations about RCT in chronic heart failure have been collected in a dedicated WHO’s register, the WHO International Clinical Trials Registry Platform (WHO-ICTRP) (www.who.int./trialsearch/AdvSearch.aspx), aimed at facilitating the public accessibility of all ongoing trials and their protocols. Interestingly, by searching this dataset, until December 1, 2008, there were 378 registered trials recruiting patients with heart failure. A total of 127 studies were excluded: 79 because of their observational design, 40 because HF was not the main target condition, 6 because they investigated the physiopathology of HF without proposing any treatment, 1 because it was registered twice, and 1 because it involved children. Among the remaining 251 CTs, 64 CTs (25.5 %) directly excluded patients by an upper age limit. In addition, in the majority of the remaining trials, high rates of other exclusion criteria, such as the presence of comorbidity, cognitive impairment, physical disabilities, polypharmacy, communication barriers, or visual or hearing deficits, indirectly limited the inclusion of older individuals. Moreover, 91 trials (36.3 % (n = 91) didn’t recruit patients with short life expectancy, while 32 (12.5 %) excluded patients with cognitive impairment (only in few cases justified by educational or behavioral purposes). Other exclusion criteria were physical disability (13.9 %) and general disability (2 %) [6]. In conclusion, the PREDICT study [6] clearly showed that available evidence-based information on the management of heart failure was based on RCT poorly representative of advanced decades; this is quite paradoxical, due to the fact that the incidence and prevalence of heart failure is particularly high in older subjects.