Elderly population clinical studies

Different drugs require different programs to develop sufficient evidence to gain marketing approval. Special population clinical study requirements are important (e.g., the elderly or children). Ultimately, the aim of this gargantuan clinical development program is to establish sufficient cause, safety, and efficacy to allow a new drug to be added to the physician s therapeutic armamentarium for the benefit of patients. 

With regard to its effects on cognitive performance in the target population, the SSRI sertraline appears to be the most thoroughly studied newer antidepressant. Lane and O Hanlon (1999) listed three controlled clinical studies with fluoxetine and three with sertraline however, all three trials with fluoxetine and one of the trials with sertraline were not sufficiently powered to demonstrate reliable differences between treatments. One of the two adequately powered studies, a comparison between nortriptyline and sertraline in elderly depressed patients (Bondareff et al., 2000 see Box 7.3), supports the notion that antidepressants with anticholinergic action (such as nortriptyline) are similarly... 

Population-based studies examining the causes, incidence and persistence of sleep disturbances in AD patients are lacking consequently, little is known about the risk factors for their development. Therefore, one must look to the literature concerning sleep disturbance in the non-demented elderly and factor this with clinical assessment of individual AD patients to make informed inferences about the AD population in order to arrive at effective treatment interventions for individual patients [4],... 

Since toxin induced chronic renal failure is theorized to occur after years of low-level toxin exposure, it stands to reason that the incidence would be clustered in elderly patients. The study of Chester et al. [172] provides indirect support that elderly patients may be at greater risk. Of the 79 patients with chronic renal failure who met age criteria of 70 year or more, 29% were classified as having chronic interstitial nephritis, a clinical diagnosis quite compatible with toxin induced renal failure and an incidence substantially higher than the 10.4% in accumulated series in which patients 50 year and older were included [173]. Furthermore, in the 2006 USRDS survey of causes of ESRD, the average age for patients with a diagnosis of interstitial nephropathy was 56 year compared to 58 years for the entire population reported [119]. In the recent analysis of the PICARD database, advanced age was associated with increased mortahty in AKI patients both at time of consultation and after initiation of dialysis treatment [38]. 

Toxicology studies conducted specifically to support juvenile or elderly populations are not evident in the published literature. The general practice is to support such populations with standard nonclinical safety studies (as discussed previously) and clinical data generated in adults. 

The very elderly population, those 80 years of age and older, has been underrepresented in clinical trials, including the SHEP and Syst-Eur studies. This population often is not treated to goal either because of a fear of lowering BP too much or because of limited data demonstrating benefit. The best available data in the very elderly come from meta-analyses. Although these data do not show reductions in mortality, they consistently show fewer strokes with active antihypertensive treatment. 

Please describe planned study population. Choice of participants should be appropriate for the indication proposed. Subjects should not have enrolled in a clinical trial during the preceding 12 weeks. Please describe how special populations such as women of childbearing age, children and the elderly will be handled in this study. Please comment on the special need for close monitoring due to safety considerations. 

R. B. Wallace, Drug utilization in the rural elderly Perspectives from a population study, in Geriatric Drug Use—Clinical and Social Perspectives (S. R. Moore and R. W. Teal, eds.), Permagon Press, New York, 1985, pp. 78-85. 

For a drug that is to be developed for a disease that occurs mainly in the elderly, it is often advisable to evaluate tolerability and pharmacokinetics in healthy elderly volunteers before clinical trials in the patient population. Dosage may need to be reduced and particular care taken when the kidney is the major organ of elimination, which should be established in the healthy young before administration to the elderly. It should be remembered that the GFR in the healthy elderly with normal plasma creatinine and urea is generally much lower than that in the young. One reason why healthy elderl/ studies have... 

Can some important questions concerning development and clinical use of this drug in the elderly be answered by a population screen approach or will specific elderly study subject trials be required ... 

Ramelteon is available in 8-mg tablets for oral administration. The current maximum dosage is 8 mg administered at night however, during trials, up to 16 mg was studied. Ramelteon should be used with caution in elderly patients because plasma levels were twice those in healthy adults in clinical trials. Ramelteon should not be used by patients with severe hepatic impairment. This medication has been evaluated in moderate sleep apnea and chronic obstructive pulmonary disease and appeared to be safe to administer in this population. Ramelteon was not studied in subjects with severe sleep... 

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