Hawthorne Effect with Transient Behavioral and Biochemical Changes in a Randomized Controlled Sleep Extension Trial of Chronically Short-Sleeping Obese Adults: Implications for the Design and Interpretation of Clinical Studies

Abstract

ObjectiveTo evaluate the effects of study participation per se at the beginning of a sleep extension trial between screening, randomization, and the run-in visit.DesignSubjects were screened, returned for randomization (Comparison vs. Intervention) after 81 days (median), and attended run-in visit 121 days later.SettingOutpatient.PatientsObese (N = 125; M/F, 30/95; Blacks/Whites/Other, N = 73/44/8), mean weight 107.6±19.7 kg, <6.5 h sleep/night.InterventionNon-pharmacological sleep extension.MeasurementsSleep duration (diaries and actigraphy watch), sleep quality (Pittsburgh Sleep Quality Index), daily sleepiness (Epworth Sleepiness Scale), fasting glucose, insulin and lipids.ResultsPrior to any intervention, marked improvements occurred between screening and randomization. Sleep duration increased (diaries: 357.4 ±51.2 vs. 388.1±48.6 min/night; mean±SD; P<0.001 screening vs. randomization; actigraphy: 344.3 ±41.9 vs. 358.6±48.2 min/night; P<0.001) sleep quality improved (9.1±3.2 vs. 8.2±3.0 PSQI score; P<0.001), sleepiness tended to improve (8.9±4.6 vs. 8.3±4.5 ESS score; P = 0.06), insulin resistance decreased (0.327±0.038 vs. 0.351±0.045; Quicki index; P<0.001), and lipids improved, except for HDL-C. Abnormal fasting glucose (25% vs. 11%; P = 0.007), and metabolic syndrome (42% vs. 29%; P = 0.007) both decreased. In absence of intervention, the earlier metabolic improvements disappeared at the run-in visit.LimitationsRelatively small sample size.ConclusionsImprovements in biochemical and behavioral parameters between screening and randomization changed the “true” study baseline, thereby potentially affecting outcome. While regression to the mean and placebo effect were considered, these findings are most consistent with the “Hawthorne effect”, according to which behavior measured in the setting of an experimental study changes in response to the attention received from study investigators. This is the first time that biochemical changes were documented with respect to the Hawthorne effect. The findings have implications for the design and conduct of clinical research.Trial RegistrationClinicalTrials.gov NCT00261898.

Improved sleep quality in older adults with insomnia reduces biomarkers of disease risk: Pilot results from a randomized controlled comparative efficacy trial

“…53 Similarly, there is growing interest in developing interventions to treat insomnia as a means to improve metabolic regulation and reduce type 2 diabetes, 54 including an ongoing trial for sleep extension in an obese sample. 55 In light of this work, and the present results, additional treatment trials are warranted.…”

The development of a clinically relevant sleep modification protocol for youth with Type 1 diabetes.

“…The benefit of different “doses” of additional sleep has not been tested. However, put in perspective, certain pharmacological treatments deemed to be clinically efficacious to target sleep problems produce a ~15 minute increase in TST (Cizza, Piaggi, Rother, & Csako, 2014; Roth, Hull, Lankford, Rosenberg, & Scharf, 2008). …”

“…As responses to our exit surveys indicated, one possible explanation for this finding is that these families were expecting to find out how their adolescents could get more sleep (even though we did not state this as the purpose). The impact of participants’ expectations entering a sleep extension study was illustrated in another recent trial in which adults with obesity experienced improvements in overall health even prior to randomization (Cizza, Piaggi, Rother, & Csako, 2014). One solution may be to not prime participants that the sole focus of the study is related to sleep or to do a full cross-over design in which all participants experience both experimental conditions.…”

Placebo Effects: From the Neurobiological Paradigm to Translational Implications

“…A recent study on obesity (Cizza et al, 2014) showed that improvements in biochemical (fasting glucose, insulin, lipids) and behavioral (sleep duration/quality) parameters occurred between screening and randomization of the patients. These findings are consistent with the Hawthorne effect, which implies that behavior measured in the setting of an experimental study changes in response to the attention received from study investigators (Last, 1983).…”

“…As becomes clear from these findings, both the social propagation of expectations and the Hawthorne effect (Cizza et al, 2014) may influence the baseline of biochemical and behavioral parameters before patients are randomized to either placebo or active treatment, thereby potentially affecting the outcome of a study. In addition to the control and assessment of learning and expectation discussed earlier, future clinical trials should therefore also consider these elements.…”