Characteristics of Randomized Controlled Trials Designed for Elderly: A Systematic Review

<div><p>Objectives</p><p>To quantify the proportion of randomized controlled trials (RCTs) specifically designed for elderly, and to assess their characteristics, as compared to RCTs not specifically designed for elderly.</p><p>Design</p><p>Review and synthesis of published literature.</p><p>Measurements</p><p>We searched PubMed for articles published in the year 2012. We included RCTs. Articles were excluded if not conducted with human subjects or if findings of secondary analyses were reported. A random sample of 10% was drawn and of this selection the following trial characteristics were extracted: sample size, disease category, age of sample, and age-related inclusion criteria. Clinical trials were defined to be specifically designed for elderly if a lower age cut-off of ≥ 55 years was used, or when participants had an average age of ≥ 70 years.</p><p>Results</p><p>The search strategy yielded 26,740 articles, from which a random sample was drawn, resulting in 2375 articles. After exclusion, data was extracted from 1369 publications. Of these 1369 RCTs, 96 (7%) were specifically designed for elderly. In comparison with trials not designed for older adults, trials designed for elderly contained a significantly larger median number of participants (125 vs. 80, p = 0.008) significantly more trials designed for elderly fell into the disease categories eye (6% vs. 2%, p = 0.005), musculoskeletal (13% vs. 7%, p = 0.023) and circulatory system (16% vs. 9%, p = 0.039). No significant difference was observed with regard to the other disease categories.</p><p>Conclusion</p><p>There is a low proportion of RCTs specifically designed for elderly. As older patients will increasingly form the majority in medical practice, there is an urgent need for stronger evidence for the formulation of treatment guidelines specifically for older adults.</p></div

Disease categories of 1369 included RCTs.

<p>¹ Pearson’s Chi square test</p><p>Disease categories of 1369 included RCTs.</p

The representation of elderly in 1369 randomized controlled trials performed in 2012.

<p>Pie chart showing the amount and proportion of randomized controlled trials designed for elderly.</p

Main trials characteristics of 1369 included RCTs.

<p>* Data are based on 1240 (91%) trials</p><p>** Data are based on 787 (57%) trials</p><p>¹ If trial participants were aged ≥ 55 years, or with an average age of ≥ 70 years</p><p>² Interquartile range, difference between 25^th and 75^th percentile is reported</p><p>³ P for difference between trials specifically designed for elderly and trials not specifically designed for elderly, tested with an Independent-Samples Mann-Whitney U test</p><p>Main trials characteristics of 1369 included RCTs.</p

Flow chart for inclusion of studies.

<p>PRISMA flow chart of the results from the performed search strategy and selection process.</p

External validity of randomized controlled trials in older adults, a systematic review

<div><p>Background</p><p>To critically assess the external validity of randomized controlled trials (RCTs) it is important to know what older adults have been enrolled in the trials. The aim of this systematic review is to study what proportion of trials specifically designed for older patients report on somatic status, physical and mental functioning, social environment and frailty in the patient characteristics.</p><p>Methods</p><p>PubMed was searched for articles published in 2012 and only RCTs were included. Articles were further excluded if not conducted with humans or only secondary analyses were reported. A random sample of 10% was drawn. The current review analyzed this random sample and further selected trials when the reported mean age was ≥ 60 years. We extracted geriatric assessments from the population descriptives or the in- and exclusion criteria.</p><p>Results</p><p>In total 1396 trials were analyzed and 300 trials included. The median of the reported mean age was 66 (IQR 63–70) and the median percentage of men in the trials was 60 (IQR 45–72). In 34% of the RCTs specifically designed for older patients somatic status, physical and mental functioning, social environment or frailty were reported in the population descriptives or the in- and exclusion criteria. Physical and mental functioning was reported most frequently (22% and 14%). When selecting RCTs on a mean age of 70 or 80 years the report of geriatric assessments in the patient characteristics was 46% and 85% respectively but represent only 5% and 1% of the trials.</p><p>Conclusion</p><p>Somatic status, physical and mental functioning, social environment and frailty are underreported even in RCTs specifically designed for older patients published in 2012. Therefore, it is unclear for clinicians to which older patients the results can be applied. We recommend systematic to transparently report these relevant characteristics of older participants included in RCTs.</p></div

Proportion of RCT’s in older patients that report on different geriatric assessments*.

<p>Showing the distribution of different geriatric measurements and expressed as percentage of the total trials (n = 300). *Some articles reporting more than one domain: 14 articles reporting two geriatric domains, eight articles reporting three geriatric domains and only one article reports four geriatric domains.</p

Univariate all-cause mortality risks for sex-dependent quartiles of laboratory results included in the laboratory profile (n = 562).

<p>Data represent hazard ratios and 95% confidence intervals, calculated with the univariate Cox-proportional hazard model.</p><p>Laboratory results are divided into sex-dependent quartiles.</p><p>25th, 50th and 75th percentile limits of laboratory results stratified for sex:</p><p>Hemoglobin: male 12.5–13.4–14.2 g/dL; female 12.0–12.8–13.6 g/dL.</p><p>High-density lipoprotein cholesterol: male 35.5–42.5–51.7 mg/dL; female: 41.7–52.1–61.8 mg/dL.</p><p>Alanine transaminase: male 11–15–20 U/L; female: 11–14–17 U/L.</p><p>Albumin: male: 4.0–4.2–4.4 g/dL; female: 4.0–4.2–4.4 g/dL.</p><p>Creatinin clearance: male: 39.4–47.2–53.9 ml/min; female: 36.8–43.4–50.8 ml/min.</p><p>C-reactive protein: male: 2–4–8 mg/L; female: 1–4–8 mg/L.</p><p>Homocysteine: male: 1.47–19.8–25.6 mg/L; female: 15.0–17.9–22.8 mg/L.</p>*<p>highest to lowest quartile.</p

Nonfasting liver enzymes and triglycerides in offspring of long-lived siblings and control subjects.

<p>Results are from linear mixed models, correcting for age, gender, and correlation of sibling relationship (model 1) and additionally for smoking, body mass index, alcohol use in g/day and number of hepatotoxic medications (model 2). Models were fitted for natural log-transformed values of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), and LnTriglycerides. Geometric means (95% confidence interval) are reported for transformed variables.</p

Association between liver biochemical test parameters and serum glucose.

<p>Tertiles of plasma LnALT, LnAST, LnGGT and serum LnTriglyceride (TG) (mmol/L) in association with nonfasting serum levels (mmol/L) of glucose. Asterisks (*p<0.05, **p<0.01, ***p<0.001) represents significant difference between groups using linear regression analysis, correcting for relation to sibling relationship, age, gender, smoking, alcohol use in g/day, and number of hepatotoxic medication. NS: not significant.</p