How representative are insomnia clinical trials?

Abstract

Study Objectives: To address the question of how representative subjects studied in hypnotic clinical trials are of the broader insomnia population, this study assessed initial contact rates and reasons for inclusion and exclusion during recruitment to an efficacy trial and to a safety trial of Food & Drug Administration (FDA) approved hypnotics. Methods: Otherwise heathy persons meeting Diagnostic Statistical Manual, Fourth Edition, Revised (DSM-IVR) criteria for insomnia were recruited. In one study, persons 32-65 yrs, were invited to a 12 month trial of nightly use of zolpidem or placebo. In the other persons 21-64 yrs with driver’s licenses were recruited to test the effects of a hypnotic on live on-the-road driving ability. In both studies screening was conducted through an initial telephone interview followed by a clinic visit. Results: In the United States (US) study 13% (n=410) of 3180 initial contacts and in the Netherlands (NL) study 67% (n=53) of the 79 initial contacts proceeded to the clinic visit. Of those at clinic 25% of US and 37% of NL participants failed to meet additional insomnia criteria. Mental health exclusions accounted for 24% of US and 23% of NL participants and medical problems accounted for 23% of US and 9% NL exclusions. Finally 20% of US and 26% of NL participants were excluded for drug use/abuse histories. After all screening 4% of the initial US contacts and 0% of the NL contacts entered the study. Conclusions: These data suggest persons entering insomnia hypnotic clinical trials are a highly selected sample that is unlikely to be representative of the broad insomnia population or the population of potential medication users.

Advantages and Limitations of Naturalistic Study Designs and Their Implementation in Alcohol Hangover Research

“…Unfortunately, applying a large number of eligibility criteria usually results in a considerable number of screening failures (i.e., participants not meeting all criteria for participation) or drop-outs and compliance failures (i.e., participants discontinuing or failing to adhere to the study protocol). This is commonly seen in RCTs [16][17][18]. In addition, a number of people may not participate in the first place when they are informed about the strict lifestyle rules and the hassle of screening procedures (e.g., blood drawings and medical examinations).…”

“…The extent to which RCT participants in drug development are representative for the patient population can therefore be questioned [17,18]. While some 'safety-related' eligibility criteria are obviously necessary, other eligibility criteria (e.g., cut off values for body weight ranges) are often not strongly justified by supporting scientific evidence [16].…”

Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit

“…Whatever weak evidence for benefits of hypnotics there has been came mainly from carefully selected groups of patients with diagnosed insomnia and few if any comorbidities or contraindications, and who generally did not use opiates or other sedatives or excess alcohol 181 . There are no clinical trials data demonstrating benefit among patients with multiple comorbidities and contraindications while lacking diagnosed insomnia, but such vulnerable patients are the majority of patients receiving hypnotics.…”

A pragmatic effectiveness randomized controlled trial of duration of psychiatric hospitalization in a trans-diagnostic sample of patients with acute mental illness admitted to a ward with either blue depleted evening lighting or normal lighting conditions

“…The observations noted have increased awareness of the need to stabilize sleep-wake cycles in individuals with major mental disorders and highlighted the importance of providing interventions targeted at circadian dysrhythmias as an adjunct to other treatments for acute illness episodes [14]. Psychological and pharmacological interventions are efficacious approaches for sleep-wake cycle disturbances in adults without comorbid mental disorders [15][16][17]. However, their use in individuals with an acute exacerbation of a major mental illness can be problematic, including attenuation of the benefit-to-risk ratio for therapies or contra-indications to the use of some medications [15][16][17].…”

“…Psychological and pharmacological interventions are efficacious approaches for sleep-wake cycle disturbances in adults without comorbid mental disorders [15][16][17]. However, their use in individuals with an acute exacerbation of a major mental illness can be problematic, including attenuation of the benefit-to-risk ratio for therapies or contra-indications to the use of some medications [15][16][17]. Partly as a response to these concerns, but also because of new research on circadian rhythms, attention has shifted to the potential role of interventions based on controlled exposures to environmental stimuli that act on biological rhythms [18].…”