<p>Recruitment and inclusion procedures as “pain killers” in clinical trials?</p>

Abstract

Background Recruitment and inclusion procedures in clinical trials are time critical. This holds particularly true for studies investigating patients with fluctuating symptom patterns, like those with chronic neck pain. In a feasibility study on neck pain, we found a clinically relevant decrease in pain ratings within the recruitment period. This paper analyses the phenomenon and gives recommendations for recruitment procedures in clinical trials on pain. Methods Changes in pain intensity scores of 44 chronic neck pain patients (6 males and 36 females; mean age: 45.3±13.2 years) between the first telephone contact and baseline assessment were analyzed. Inclusion criterion was a mean pain intensity of ≥40 on a 0–100 numerical rating scale during the last three months. Statistical analyses were performed using ANOVA and parametric/non-parametric correlation coefficients. Results Average pain intensity score decreased significantly from 60.3±13.3 at telephone interview to 38.1±21.7 at baseline assessment. This represents a relative change of 36.8%. A weak but significant negative correlation was found between number of days between assessments and pain rating differences. There was a positive correlation between change of pain intensity and the pain level at the first contact, indicating that the decreased pain ratings over time were also dependent on the initial pain rating. Conclusions The clinically significant changes in pain intensity were weakly related to waiting time and moderately dependent on initial pain intensity, suggesting regression to the mean. The natural course of the disease and the Hawthorne effect are also discussed as contributing factors.

Recruitment and retention for chronic pain clinical trials: a narrative review

“…49,129 Lengthy delays from patient identification to recruitment to study initiation can cause dropout when an alleviation of pain symptoms (or simple regression to the mean) occurs during the waiting period or over the course of the trial because patients may no longer see the benefit in participating or continuing to participate. 91,101,101,129 To mitigate timing issues, researchers in 1 study used dedicated staff not only for study enrollment (including recruitment, screening, and consenting) but also for actively connecting with healthcare providers weekly or even daily to identify eligible patients and follow-up immediately with those expressing interest in the study. Staff also scheduled and placed reminder calls.…”

Defining and evaluating the Hawthorne effect in primary care, a systematic review and meta-analysis

“…Of the 15 purposely selected reports in primary care, outpatient clinics, or healthy subjects in the meta-analysis branch, the appraisal of the HE was based on a retrospective cohort pre–post intervention analysis in one study ( 72 ), in three studies on a post-hoc comparison of the RCT population to a non-RCT population ( 24 , 30 , 94 ), in three studies on the comparison of study parameters between enrollment and randomization in an RCT ( 28 , 43 , 51 ), in two studies on the comparison of persons consenting vs. not consenting to participate in a study ( 45 , 67 ), in two studies on the follow-up of study populations exposed to repeated measurements ( 77 , 95 ), and in four studies comparing a population being aware of exposure to observation or assessment to a population who were not aware ( 33 , 64 , 83 , 96 ). The main binary outcomes that were inputted in the tables of the review manager to compute an effect size and standard error were sleeping time ( 28 ), anti-malarial drug prescriptions ( 33 ), time up and go measure ( 51 ), self-reported alcohol consumption ( 96 ), pain intensity ( 43 ), and subjective shared decision-making ( 95 ) in the RCTs or RCT feasibility studies. It was an antibiotic selection in a quasi-experimental RCT ( 30 ).…”

“…According to the Cochrane tool ( 19 ), in the definition branch, six studies had a low risk of bias ( 27 – 29 , 31 , 32 , 39 ), 18 studies had a moderate risk of bias ( 24 , 26 , 30 , 33 – 36 , 38 , 43 – 46 , 48 , 50 , 52 , 58 , 69 , 79 ), 38 had an important risk of bias ( 21 , 22 , 37 , 40 – 42 , 49 , 51 , 54 , 56 , 57 , 59 – 68 , 70 – 72 , 74 – 78 , 80 – 88 ), and two studies had a very important risk of bias ( 23 , 73 ). Nine studies were not assessable with the tool (protocols or qualitative/mixed methods studies) ( 13 , 25 , 47 , 53 , 89 – 93 ).…”

“…Of the 74 selected reports in the definition branch, 15 were randomized controlled trials (RCTs) (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39), two were not randomized controlled trials (40,41), three were studies nested in RCTs (42)(43)(44), seven were retrospective reanalysis or discussions of RCTs (23,24,(45)(46)(47)(48)(49), three were pilot studies prior to an RCT (50)(51)(52), and one was an RCT protocol (53). Further, there were 18 observational studies (54-71), 18 pre-post intervention studies or audits (21,22,(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)…”

“…As noted, patients change their behavior by the start of the trial, and baseline values are prone to the RTM (24,28,43,51). For these reasons, it can be recommended to separate enrollment in trials and randomization by about 1 month and to repeat outcome measures at the randomization visit.…”