RCT Participants Research Articles

Baseline Racial Differences in ENABLE-CHF-PC Trial Participants

Background While recent evidence demonstrates providing early palliative care (EPC) with routine heart failure (HF) care can improve quality of life (QOL) and reduce symptom burden and healthcare use, there is limited evidence examining EPC in a racially diverse HF population in the Southeastern US. Aims To describe and explore patient (PT) and caregiver (CG) participants’ baseline sociodemographics and outcome measures focusing on racial differences. Methods We compared sociodemographics and baseline PT/CG-reported outcome measures (Kansas City Cardiomyopathy Questionnaire [KCCQ], Hospital Anxiety/Depression Scale [HADS], religious coping style, & CG burden (Montgomery Borgatta Caregiver Burden [MCBC] Scale). We then calculated racial differences in these measures using T-tests adjusted with a False Discovery Rate. Results Of 487 participants, there were 357 PTs (nWhite(W)= 157; nBlack(B)= 200) and 130 CGs (nW= 55; nB= 75). Relative to race, Black PTs were younger (nW= 65.12; nB= 62.72; d= 0.29; p= 0.037), less likely to be married (nW= 90; nB= 78; d=0. 42, p= 0.0024), less likely to have private insurance coverage (nW= 103; nB= 83; d= 0.42, p= 0.0024), less likely to have a rural residence (nw= 55, nB= 39; d=0.35; p= 0.0086). Clinically, Black PTs had a lower ejection fraction (Mw= 44.99, MB= 38.9; d= 0.38, p= 0.0047) and fewer had a DNR order (nW= 37; nB = 22; d= 0.36, p= 0.0101). Black PTs also reported more negative religious coping (Mw= 3.8; MB=3.65; d=0.32, p= 0.473). Relative to race, more Black CGs were Protestant (nw= 48, nB= 74; d= 0.39). Black CGs reported lower HADS-depression scores (Mw= 5.36, MB= 4.15; d= 0.38) and lower CG burden scores (MBCB (Mw= 45.05; MB= 42.59; d= 0.43)). Conclusion There were relevant differences in RCT participants’ demographic and clinical characteristics at baseline. It will be important to consider these differences in analyzing trial outcomes and in intervention impact. Ultimately, if racial differences are identified this presents opportunities for tailoring the cultural aspects of the intervention to improve both access to and acceptability of EPC in all HF populations. ClinicalTrials.gov Identifier: NCT02505425.

Association between sedation-analgesia and neurodevelopment outcomes in neonatal hypoxic-ischemic encephalopathy.

ObjectiveTo evaluate the association between sedation-analgesia (SA) during initial 72 hours and death/disability at 18 months of age in neonatal hypoxic-ischemic encephalopathy (HIE).DesignThis was a secondary analysis of the NICHD therapeutic hypothermia (TH) randomized controlled trial in moderate or severe HIE. Receipt of SA and anticonvulsant medications at 5 time points were considered: prior to and at baseline, 24, 48 and 72 hours of TH or normothermia. Disability was defined as mental developmental index <85, cerebral palsy, blindness, hearing impairment or Gross Motor Function Classification System 2-5.ResultsOf the 208 RCT participants, 38 (18%) infants had no exposure to SA or anticonvulsants at any of the 5 time points, 20 (10%) received SA agents only, 81 (39%) received anticonvulsants only and 69 (33%) received both SA and anticonvulsants. SA category drugs were not administered in 57% of infants while 18% received SA at ≥3 time points; 72% infants received anticonvulsants during 72 hours of intervention. At 18 months of age, disability among survivors and death/disability was more frequent in the groups receiving anticonvulsants, with (48 and 65%) or without (37 and 58%) SA, compared to groups with no exposure (14 and 34%) or SA (13 and 32%) alone. Severe HIE (aOR 3.60; 1.59-8.13), anticonvulsant receipt (aOR 2.48; 1.05-5.88) and mechanical ventilation (aOR 7.36; 3.15-17.20) were independently associated with 18-month death/disability whereas TH (aOR 0.28; 0.13-0.60) was protective. SA exposure showed no association with outcome.ConclusionsThe risk-benefits of SA in HIE needs further investigation.

Geographic Information Systems to Assess External Validity in Randomized Trials

To support claims that RCTs can reduce health disparities (i.e., are translational), it is imperative that methodologies exist to evaluate the tenability of external validity in RCTs when probabilistic sampling of participants is not employed. Typically, attempts at establishing post hoc external validity are limited to a few comparisons across convenience variables, which must be available in both sample and population. A Type 2 diabetes RCT was used as an example of a method that uses a geographic information system to assess external validity in the absence of a priori probabilistic community-wide diabetes risk sampling strategy. A geographic information system, 2009-2013 county death certificate records, and 2013-2014 electronic medical records were used to identify community-wide diabetes prevalence. Color-coded diabetes density maps provided visual representation of these densities. Chi-square goodness of fit statistic/analysis tested the degree to which distribution of RCT participants varied across density classes compared to what would be expected, given simple random sampling of the county population. Analyses were conducted in 2016. Diabetes prevalence areas as represented by death certificate and electronic medical records were distributed similarly. The simple random sample model was not a good fit for death certificate record (chi-square, 17.63; p=0.0001) and electronic medical record data (chi-square, 28.92; p<0.0001). Generally, RCT participants were oversampled in high-diabetes density areas. Location is a highly reliable "principal variable" associated with health disparities. It serves as a directly measurable proxy for high-risk underserved communities, thus offering an effective and practical approach for examining external validity of RCTs.

Real-Life and RCT Participants: Alendronate Users Versus FITs' Trial Eligibility Criterion.

We aimed to characterize incident users of alendronate from Denmark and Spain, and investigate their eligibility for participation in the pivotal Fracture Intervention Trial (FIT). This is an international cross-sectional study, where the data were obtained from the SIDIAP database (Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària) from Catalonia (Spain) and the Danish Health Registries (DHR). This study included patients who were incident users of alendronate, ≥40years old with no history of Paget's disease. Our measurements were the proportion of incident users of alendronate who were not eligible to participate in FIT. 14,316 and 21,221 subjects initiated alendronate in 2006-2007 (SIDIAP) and 2005-2006 (DHR), respectively. SIDIAP and DHR alendronate user cohorts had 2347 (16.4%) and 5275 (24.9%) subjects aged >80years old, reported 9 (0.1%) and 91 (0.4%) diagnoses of myocardial infarction, 423 (3%) and 368 (1.7%) of erosive gastro-intestinal disease, 200 (1.4%) and 1109 (5.2%) of dyspepsia, and 349 (2.4%) and 149 (0.7%) of metabolic bone disease, all of which were exclusion criteria in FIT. Men [3818 (26.7%) in SIDIAP and 3885 (18.3%) in DHR] and glucocorticoid users [1229 (8.6%) in SIDIAP and 4716 (22.2%) in DHR] were also excluded from the FIT trial. Overall, 3447 (35.4%) SIDIAP and 6228 (44.5%) (when not considering men and glucocorticoid users) DHR of incident alendronate users would have been excluded from FIT. One in two real-life users of alendronate exhibited one or more clinical characteristics that would have led to them being excluded from the FIT trial.

Clinician trialist rounds: 28. When RCT participants are lost to follow-up. Part 1: Why even a few can matter.

Clinician trialist rounds: 28. When RCT participants are lost to follow-up. Part 1: Why even a few can matter.

Recruiting RCT Participants: To Facebook or Not to Facebook?

Little is known about how best to capture the interest of potential study participants using Facebook (FB) ads. Thus, the effectiveness of 64 FB recruitment ads for HomeStyles, a nutrition interven...

Participation of elderly adults in randomized controlled trials addressing antibiotic treatment of pneumonia.

To examine how relevant current evidence on antibiotic treatment of pneumonia is for elderly adults. Systematic review. Randomized controlled trials (RCTs; N = 43) comparing different antibiotics and prospective observational studies (N = 182) published since 2005. Adults with community-acquired (CAP), healthcare-associated (HCAP), hospital-acquired (HAP), or ventilator-associated (VAP) pneumonia. Exclusion criteria that could preferentially limit participation of elderly adults were examined, subgroup or other adjusted analyses were searched for according to age, and treatment effects in participants younger than 65 in RCTs were compared with those in participants aged 65 and older. Mean participant ages in RCTs and observational studies were compared. Risk ratios (RRs) with 95% confidence intervals (CIs) for differences between older and younger adults were pooled using a fixed effect metaanalysis. No RCT reported exclusion based on an upper age limit; 100% of community CAP trials, 90% of hospitalized CAP trials, and 76% of HAP and VAP trials excluded individuals based on comorbidities. None of the RCTs reported a subgroup analysis for mortality according to age. The RR for the pooled difference in treatment failure rates between participants younger than 65 and those aged 65 and older was 1.25 (95% CI = 0.94-1.65, 12 RCTs) and between participants younger than 75 and aged 75 and older was 1.43 (95% CI = 0.98-2.09, 7 RCTs). RCT participants were significantly younger (54.0 ± 9.6) than those in observational studies of CAP (66.2 ± 8.1, P < .001). Age differences were not significant for HCAP, HAP, and VAP. Elderly adults are often excluded from RCTs of bacterial pneumonia. No data were found on the comparative efficacy of antibiotic treatment in elderly adults and the general population.

Effectiveness of the Austrian disease management programme “Therapie Aktiv” for type 2 diabetes regarding the improvement of metabolic control, risk profile and guideline adherence: 2 years of follow up

We evaluated the disease management programme (DMP) "Therapie Aktiv" for diabetes mellitus type 2 during the first year of implementation in a cluster-randomised controlled trial (RCT), which revealed an improvement of process quality, but only insignificant effects on HbA1c. To further analyse the effects of the DMP we followed up participants of the RCT for another year. After completion of the RCT, the study was continued as an open observational trial. By patient's choice, three groups were formed. Group 1 (DMP/DMP): interventions of the RCT (DMP), who remained in the DMP; group 2 (Control/DMP): controls of the RCT (usual care), who participated in the DMP during the second year; group 3 (Control/Control): controls of the RCT (usual care), who remained as controls. HbA1c. BMI, lipids, blood pressure and measures of process quality. Only 801 of 1,489 RCT participants completed the study (53.8 %). Group 1: n = 355; group 2: n = 335; group 3: n = 111. After 2 years, pre-post-analysis revealed a significant reduction of HbA1c (0.37 %, p < 0.001) in both DMP groups, and a reduction of only 0.03 % (p = 0.975) in the control group. However, the difference between the groups was not significant (p = 0.065). There was a significant improvement of process quality in the DMP groups compared with controls. The DMP clearly enhances process quality. Furthermore, the DMP yields a reduction of HbA1c within groups after 2 years, but significance is lost in between-group analysis. We conclude that the DMP has only a minor effect on metabolic control.

Scientific tools, fake treatments, or triggers for psychological healing: How clinical trial participants conceptualise placebos

Placebos are an essential tool in randomised clinical trials, where they are used to control for bias and contextual healing effects. Placebos and their effects are also studied from multiple diverse perspectives, but the perspectives of placebo recipients are seldom considered. Research shows that people form cognitive and affective representations of active treatments such as medicines, and that they use these representations to guide their behaviour; it seems reasonable to suggest that people might also think about and develop representations of placebos. We adopted a qualitative approach to examine in detail how participants in one RCT, conducted in the USA, conceptualised placebos. 12 people were interviewed 3 times each, at the start, middle, and end of a trial of placebo effects and acupuncture for Irritable Bowel Syndrome (IBS). The interview data were analysed inductively and we identified four ways in which the participants conceptualised placebos: placebos are necessary for research; placebo effects are fake; placebo acupuncture is not real acupuncture; placebos have real effects mediated by psychological mechanisms. Participants’ conceptualisations of placebos were dynamic and situated in a broader psychological and socio-cultural context. Seeing placebo effects as legitimate seemed to be facilitated by having more holistic models of healing, viewing IBS as psychological, and seeing treatment as multifactorial. However, some participants maintained a negative view of placebo effects (e.g. as illusions) that was apparently inconsistent with their other beliefs (e.g. in mind-body healing mechanisms). This may indicate a dominance of negative discourses around placebos at a socio-cultural level. Negative views of placebos are inconsistent with evidence that placebo treatments can have positive effects on symptoms. RCT participants should be informed about potential benefits of placebo treatments to avoid misunderstandings and unease. Future work should improve methods of providing participants with full accurate information about placebos and their effects.

Participant demographics reported in "Table 1" of randomised controlled trials: a case of "inverse evidence"?

IntroductionData supporting external validity of trial results allows clinicians to assess the applicability of a study's findings to their practice population. Socio-economic status (SES) of trial participants may be critical to external validity given the relationship between social and economic circumstances and health. We explored how this is documented in reports of RCTs in four major general medical journals.MethodsThe contents lists of four leading general medical journals were hand searched to identify 25 consecutive papers reporting RCT results in each journal (n = 100). Data on demographic characteristics were extracted from each paper's Table 1 only (or equivalent).ResultsAuthors infrequently reported key demographic characteristics relating to SES of RCT participants. Age and gender of participants were commonly reported. Less than 10% reported occupational group, employment status, income or area based measures of disadvantage.ConclusionsWithout adequate reporting of key indicators of SES in trial participants it is unclear if lower SES groups are under-represented. If such groups are systematically under-recruited into trials, this may limit the external validity and applicability of study findings to these groups. This is in spite of the higher health-care need in more disadvantaged populations. Under-representation of low SES groups could underestimate the reported effect of an intervention for those with a higher baseline risk. The marginal benefit identified in a trial with poor or no representation of lower SES participants could significantly underestimate the potential benefit to a low SES community. More transparency in this reporting and greater attention to the impact of SES on intervention outcomes in clinical trials is needed. This could be considered in the next revision of the CONSORT statement.

Acupuncture for osteoarthritis: A qualitative analysis to interpret the results of a randomised controlled trial

Objective To develop explanations for the quantitative findings of an RCT by systematically interrogating data from the nested qualitative study. Design Qualitative study (narrative interviews and framework analysis) nested within an RCT. Participants A total of 27 RCT participants were purposively selected to interview, to encompass all treatment conditions. Setting The single-blind RCT examined the efficacy of real acupuncture for pain relief in hip and knee osteoarthritis. Patients were randomised to 3 treatment conditions (real acupuncture vs 2 placebo treatments) and 2 consultation conditions (empathic vs non-empathic). The study involved 3 experienced acupuncturists who delivered all interventions. Findings Interviewees were active participants who sought to make meaning of their experiences in the trial. They wanted to try acupuncture and thought it might benefit them, thus subverting patient equipoise. Interviewees sought to determine whether they were receiving real treatment and drew on cues including perceived outcomes, treatment sensations, and practitioner behaviours. Evidence for a reciprocal process is outlined in which interviewees’ perceptions of treatment veracity and outcomes were mutually reinforcing. The most successful practitioner was seen as an authoritative doctor. Interviewees reported colluding with practitioners in non-empathic consultations, and inferred empathy from experiences associated with the trial but outside the protocol treatments. Conclusions This nested qualitative analysis offered novel insights into the RCT findings that would not have been possible from the quantitative data alone. Conceptualising and understanding RCT subjects as active participants has important implications for trial design particularly for interventions such as acupuncture when equipoise is unlikely.

A randomised controlled trial of lay-led self-management for people with multiple sclerosis

Objective To determine the impact of the Chronic Disease Self-Management Course (CDSMC) on people with multiple sclerosis (MS). Methods 2-group, randomised, controlled trial with Intervention Group (IG) and Waiting-List Control Group (WLCG). Additional data were collected from a Comparison Group (CG) who chose not to attend the CDSMC. Participants completed baseline questionnaires; IG participants attended the CDSMC immediately; all participants were assessed at 4-months and 12-months. Results 216 baseline questionnaires were returned; 73% were female, mean age 51.1 years, mean disease duration 12.0 years. Results showed that the CDSMC had an impact on self-management self-efficacy (ES 0.30, p = 0.009 for the IG) and MSIS physical status (ES 0.12 for the IG, p = 0.005). There were no other statistically significant changes. However, trends towards improvement on depression (ES 0.21 for the IG, p = 0.05) and MS self-efficacy (ES 0.16 for the IG, p = 0.04) were noted. All improvements were maintained at 12-months. At baseline, CG participants were older, had longer disease duration ( p < 0.01) and less anxiety ( p = 0.009) compared to RCT participants. Conclusion The CDSMC provides some small positive effects for people with MS. Motivation to attend may be linked to psychological distress and disease duration. Practice implications The CDSMC may be of value for those with mild anxiety/depression who need extra support. Attendance early in the disease course is recommended.