Randomized Controlled Trials Participants Research Articles

Abstract A33: Engaging Linguistically and Ethnically Diverse Low Income Women in Health Research

Abstract Underserved breast cancer patients and survivors are typically offered fewer opportunities to participate in cancer research. To address this disparity, a community based navigator program, Shanti's Margot Murphy Breast Cancer Program (Shanti) initiated a collaboration with UCSF researchers and BreastCancerTrials.org (BCT), a nonprofit clinical trials matching service to explore the potential role of a trusted community-based organization as a source of culturally appropriate education and access to clinical trial information. The pilot study identified guiding principles for development of our Health Research Engagement Intervention (HREI): a) within the context of a trusted relationship, navigators provide education about health research and increase access to information about ongoing breast cancer studies, emphasizing the range of treatment and non-treatment quality-of-life and observational studies; b) provide education and information at a time when the patient is not in the initial crisis of diagnosis; and c) address systems barriers to health research information and participation. This mixed method study includes: 1) capacity-building for the CBO partner (Shanti) and the health research access point (BCT) to reduce system barriers and to conduct evaluations of enhancements to both; 2) a prospective randomized controlled trial (RCT) of the HREI with pre and post surveys; and 3) qualitative evaluation of the trial implementation. The trial's primary outcome is health research information-seeking behavior. Secondary outcomes include health research knowledge, attitudes towards research participation, and health empowerment. To enhance capacity and address system barriers, we added a multilingual (English, Cantonese, Spanish) voicemail system to BCT's helpline, trained staff to use professional healthcare interpreters and enhanced the design of the BCT website for easier navigation by lower health literacy patients. At Shanti, we trained care navigators on health research and the HREI and implemented a Client Tracking Calendar to improve identification of and projections for eligible clients. All Shanti clients who speak English, Cantonese or Spanish and have “low care navigation needs” are eligible (i.e. client may or may not still be undergoing treatment but is no longer in the crisis of initial diagnosis or burdened by treatment protocols). Eighty-six of 150 RCT participants have been enrolled to date and 74 have completed the trial. Interim analyses indicate that participants in the intervention group were more likely than those in the control group to seek health research information. Through sustainable and synergistic capacity building enhancements to two breast cancer organizations, this study is working to increase equity in access to health research information and research participation opportunities for diverse underserved breast cancer patients and survivors. The HREI, if proven effective after completion of the trial, has the long-range potential to reduce disparities in access to health research information and participation opportunities, and thereby to impact progress of breast cancer research. Furthermore, the HREI is a dissemination-ready navigator protocol with the potential for replication in underserved communities nationally. Note: This abstract was not presented at the conference. Citation Format: Alyssa Nickell, Elly Cohen, Susan Stewart, Janice Ka Yan Cheng, Katie Lawlor, Susan Colen, Nancy Burke, Claudia Guerra, Galen Joseph. Engaging Linguistically and Ethnically Diverse Low Income Women in Health Research. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A33.

A community-based primary prevention programme for type 2 diabetes mellitus integrating identification and lifestyle intervention for prevention: a cluster randomised controlled trial

BackgroundPrevention of type 2 diabetes mellitus (T2DM) is a global priority; however, there is a lack of evidence investigating how to effectively translate prevention research into a primary care setting.Objectives(1) To develop and validate a risk score to identify individuals at high risk of T2DM in the UK; and (2) to establish whether or not a structured education programme targeting lifestyle and behaviour change was clinically effective and cost-effective at preventing progression to T2DM in people with prediabetes mellitus (PDM), identified through a risk score screening programme in primary care.DesignA targeted screening study followed by a cluster randomised controlled trial (RCT), with randomisation at practice level. Participants were followed up for 3 years.SettingA total of 44 general practices across Leicestershire, UK. The intervention took place in the community.ParticipantsA total of 17,972 individuals from 44 practices identified through the risk score as being at high risk of T2DM were invited for screening; of these, 3449 (19.2%) individuals attended. All received an oral glucose tolerance test. PDM was detected in 880 (25.5%) of those screened. Those with PDM were included in the trial; of these, 36% were female, the average age was 64 years and 16% were from an ethnic minority group.InterventionPractices were randomised to receive either standard care or the intervention. The intervention consisted of a 6-hour group structured education programme, with an annual refresher and regular telephone contact.Main outcome measuresThe primary outcome was progression to T2DM. The main secondary outcomes were changes in glycated haemoglobin concentrations, blood glucose levels, cardiovascular risk, the presence of metabolic syndrome, step count and the cost-effectiveness of the intervention.ResultsA total of 22.6% of the intervention group did not attend the education and 29.1% attended all sessions. A total of 131 participants developed T2DM (standard care,n = 67; intervention,n = 64). There was a 26% reduced risk of T2DM in the intervention arm compared with standard care, but this did not reach statistical significance (hazard ratio 0.74, 95% confidence interval 0.48 to 1.14;p = 0.18). There were statistically significant improvements in glycated haemoglobin concentrations, low-density lipoprotein cholesterol levels, psychosocial well-being, sedentary time and step count in the intervention group. The intervention was found to result in a net gain of 0.046 quality-adjusted life-years over 3 years at a cost of £168 per patient, with an incremental cost-effectiveness ratio of £3643 and a probability of 0.86 of being cost-effective at a willingness-to-pay threshold of £20,000.ConclusionsWe developed and validated a risk score for detecting those at high risk of undiagnosed PDM/T2DM. We screened > 3400 people using a two-stage screening programme. The RCT showed that a relatively low-resource pragmatic programme may lead to a reduction in T2DM and improved biomedical and psychosocial outcomes, and is cost-effective.LimitationsOnly 19% of those invited to screening attended, which may limit generalisability. The variation in cluster size in the RCT may have limited the power of the study.Future workFuture work should focus on increasing attendance to both screening and prevention programmes and offering the programme in different modalities, such as web-based modalities. A longer-term follow-up of the RCT participants would be valuable.Trial registrationCurrent Controlled Trials ISRCTN80605705.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

External validity of a contemporaneous primary percutaneous coronary intervention trial in patients with acute ST-elevation myocardial infarction: insights from a single-centre investigation

Randomised controlled trials (RCTs) represent the most robust source of evidence-based medicine. However, the generalisability of RCTs is limited by the inclusion of selected populations. We sought to assess the external validity of a contemporary trial including patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Patients presenting to Bern University Hospital during the inclusion period of the COMFORTABLE AMI trial were divided into three groups: RCT participants (41%), eligible not included (17.5%), and excluded patients (41.5%). Major adverse cardiac events (MACE) were defined as one-year death and myocardial infarction. RCT participants compared with RCT-eligible patients had comparable baseline characteristics and outcomes; however, excluded patients differed in risk and had higher rates of MACE (HR 3.63, 95% CI: 2.03-6.48, p<0.001), death (HR 6.23, 95% CI: 2.93-13.24, p<0,001) and definite/probable stent thrombosis (HR 3.63, 95% CI: 1.79-7.36, p<0.001). Inability to provide consent was the most frequent exclusion criterion and was independently associated with an increased risk for MACE (HR 6.85, 95% CI: 3.97-11.81, p<0.001). In this single-centre investigation, results from the COMFORTABLE AMI trial appeared applicable to a broad representation of RCT-eligible patients. However, patients excluded from the trial represented a higher-risk population with impaired clinical outcomes and a lower adherence to cardiovascular medication.

Eligibility of real-life patients with COPD for inclusion in trials of inhaled long-acting bronchodilator therapy.

BackgroundManagement guidelines of chronic obstructive pulmonary disease (COPD) are mainly based on results of randomised controlled trials (RCTs), but some authors have suggested limited representativeness of patients included in these trials. No previous studies have applied the full range of selection criteria to a broad COPD patient population in a real-life setting.MethodsWe identified all RCTs of inhaled long-acting bronchodilator therapy, during 1999–2013, at ClinicalTrials.gov and translated trial selection criteria into definitions compatible with electronic medical records. Eligibility was calculated for each RCT by applying these criteria to a uniquely representative, well-characterised population of patients with COPD from the Optimum Patient Care Research Database (OPCRD).ResultsMedian eligibility of 36 893 patients with COPD for participation in 31 RCTs was 23 % (interquartile range 12–38). Two studies of olodaterol showed the highest eligibility of 55 and 58 %. Conversely, the lowest eligibility was observed in two studies that required a history of exacerbations in the past year (3.5 and 3.9 %). For the patient subgroup with modified Medical Research Council score ≥2, the overall median eligibility was 27 %.ConclusionsBy applying an extensive range of RCT selection criteria to a large, representative COPD patient population, this study highlights that the interpretation of results from RCTs must take into account that RCT participants are variably, but generally more representative of patients in the community than previously believed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0433-5) contains supplementary material, which is available to authorized users.

Generalizability of Patients With Rheumatoid Arthritis in Biologic Agent Clinical Trials.

Randomized controlled trials (RCTs) have consistently demonstrated the efficacy of biologic agents in treating patients with rheumatoid arthritis (RA) who satisfy strict eligibility criteria, yet studies report that a majority of RA patients in the US have had biologic treatment exposure. We identified the proportion of RA patients in clinical practice satisfying entry criteria for biologic agent RCTs. Eligibility criteria of 30 RCTs of 10 Food and Drug Administration-approved biologic agents to treat RA were reviewed, summarized, and applied to 2 observational clinical cohorts: the Veterans Affairs Rheumatoid Arthritis registry (VARA; n = 1,523) and the Rheumatology and Arthritis Investigational Network Database (RAIN-DB; n = 1,548). Patients at a single clinical encounter were assessed for overall trial eligibility as well as eligibility across 3 domains: demographics, disease activity, and medication exposure. The mean percentage of patients that satisfied eligibility criteria was 3.7% (interquartile range [IQR] 1.5-3.1) in VARA and 7.1% (IQR 4.4-7.7) in RAIN-DB. Ineligibility was most often due to low disease activity, specifically low joint counts. The mean Disease Activity Score in 28 joints at enrollment was 6.59 (range 6.1-7.1) across RCTs versus 3.87 (0.07-8.69) in VARA and 3.65 (0.49-7.21) in RAIN-DB. RCTs for non-tumor necrosis factor (TNF) inhibitor biologic agents were more restrictive than RCTs for TNF inhibitors. There was no trend in eligibility by RCT study publication or drug approval date. The vast majority of RA patients from our clinical cohorts did not satisfy criteria for participation in biologic agent RCTs. These findings underscore the need for caution in extrapolating trial results to day-to-day management of RA patients and may provide insight into the differential responses to biologic agents reported in prior observational studies.

Towards onset prevention of cognition decline in adults with Down syndrome (The TOP-COG study): A pilot randomised controlled trial.

BackgroundDementia is very common in Down syndrome (trisomy 21) adults. Statins may slow brain amyloid β (Aβ, coded on chromosome 21) deposition and, therefore, delay Alzheimer disease onset. One prospective cohort study with Down syndrome adults found participants on statins had reduced risk of incident dementia, but there are no randomised controlled trials (RCTs) on this issue. Evidence is sparse on the best instruments to detect longitudinal cognitive decline in older Down syndrome adults.MethodsTOP-COG was a feasibility/pilot, double-blind RCT of 12 months simvastatin 40 mg versus placebo for the primary prevention of dementia in Alzheimer disease in Down syndrome adults aged 50 years or older. Group allocation was stratified by age, apolipoprotein E (APOE) ε4 allele status, and cholesterol level. Recruitment was from multiple general community sources over 12 months. Adults with dementia, or simvastatin contraindications, were excluded. Main outcomes were recruitment and retention rates. Cognitive decline was measured with a battery of tests; secondary measures were adaptive behaviour skills, general health, and quality of life. Assessments were conducted pre randomisation and at 12 months post randomisation. Blood Aβ40/Aβ42 levels were investigated as a putative biomarker. Results were analysed on an intention-to-treat basis. A qualitative sub-study was conducted and analysed using the Framework Approach to determine recruitment motivators/barriers, and participation experience.ResultsWe identified 181 (78 %) of the likely eligible Down syndrome population, and recruited 21 (11.6 %), from an area with a general population size of 3,135,974. Recruitment was highly labour-intensive. Thirteen (62 %) participants completed the full year. Results favoured the simvastatin group. The most appropriate cognitive instrument (regarding ease of completion and detecting change over time) was the Memory for Objects test from the Neuropsychological Assessment of Dementia in Individuals with Intellectual Disabilities battery. Cognitive testing appeared more sensitive than proxy-rated adaptive behaviour, quality of life, or general health scores. Aβ40 levels changed less for the simvastatin group (not statistically significant). People mostly declined to participate because of not wanting to take medication, and not knowing if they would receive simvastatin or placebo. Participants reported enjoying taking part.ConclusionA full-scale RCT is feasible. It will need 37 % UK population coverage to recruit the required 160 participants. Information/education about the importance of RCT participation is needed for this population.Trial registrationISRCTN67338640.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1370-9) contains supplementary material, which is available to authorized users.

Identifying the participant characteristics that predict recruitment and retention of participants to randomised controlled trials involving children: a systematic review.

BackgroundRandomised controlled trials (RCTs) are recommended as the ‘gold standard’ in evaluating health care interventions. The conduct of RCTs is often impacted by difficulties surrounding recruitment and retention of participants in both adult and child populations. Factors influencing recruitment and retention of children to RCTs can be more complex than in adults. There is little synthesised evidence of what influences participation in research involving parents and children.AimTo identify predictors of recruitment and retention in RCTs involving children.MethodsA systematic review of RCTs was conducted to synthesise the available evidence. An electronic search strategy was applied to four databases and restricted to English language publications. Quantitative studies reporting participant predictors of recruitment and retention in RCTs involving children aged 0–12 were identified. Data was extracted and synthesised narratively. Quality assessment of articles was conducted using a structured tool developed from two existing quality evaluation checklists.ResultsTwenty-eight studies were included in the review. Of the 154 participant factors reported, 66 were found to be significant predictors of recruitment and retention in at least one study. These were classified as parent, child, family and neighbourhood characteristics. Parent characteristics (e.g. ethnicity, age, education, socioeconomic status (SES)) were the most commonly reported predictors of participation for both recruitment and retention. Being young, less educated, of an ethnic minority and having low SES appear to be barriers to participation in RCTs although there was little agreement between studies. When analysed according to setting and severity of the child’s illness there appeared to be little variation between groups. The quality of the studies varied. Articles adhered well to reporting guidelines around provision of a scientific rationale for the study and background information as well as displaying good internal consistency of results. However, few studies discussed the external validity of the results or provided recommendations for future research.ConclusionParent characteristics may predict participation of children and their families to RCTs; however, there was a lack of consensus. Whilst sociodemographic variables may be useful in identifying which groups are least likely to participate they do not provide insight into the processes and barriers to participation for children and families. Further studies that explore variables that can be influenced are warranted. Reporting of studies in this field need greater clarity as well as agreed definitions of what is meant by retention.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1415-0) contains supplementary material, which is available to authorized users.

72. Addressing barriers for conducting/participating in clinical trials among cardiologists

Well conducted randomized controlled trials (RCT) provide answers to relevant clinical question with the highest level of evidence. However, cardiologist’s participation in RCTs remains disappointing low in Saudi Arabia despite the perception of its benefits for patients and clinical practice. The purpose of this study is to identify the challenges and barriers for cardiologists participation in RCTs as perceived by cardiologist’s working in King Abdul-Aziz Cardiac center, Saudi Arabia. A self-administered questionnaire was completed by cardiologists from different subspecialties working at King Abdul-Aziz Cardiac Center, Riyadh. All cardiologists working in this center were invited to participate. The questionnaire used was validated before in a previous multicenter study conducted in the United States. A total of 61 cardiologists (consultants, Associates and Assistant consultants) participated in the study with a response rate of 91%. The mean duration of clinical practice was 7.5 ± 7.9 years. Half of the cardiologists reported that they did not participate in any RCT before. Among those who participated, only 21.3% were principal investigator (PI) or co-investigator, while others only assisted in enrolling patients. Most cardiologists (90%) agreed that RCTs improve patient care and an overwhelming majority (98.4%) reported that they would like to be involved in RCTs in the future (86.9% as PI). In addition, 77.0% of the participating physicians believe that their organization is encouraging them to participate in RCTs. However, many cardiologists cited barriers to participating in RCT including lack of time (70.5%), lack of training/experience (74.5%) and lack of ancillary support staff (70.5%). This study identified a group of barriers that should be tackled in order to promote the active involvement of cardiologists in future RCTs. Most cardiologist are very enthusiastic about RCT, but they lack the skills and support staff to initiate RCTs. Future efforts should tackle these identified barriers to increase participation in multicenter and investigator initiated clinical trials.

Optimising recruitment and informed consent in randomised controlled trials: the development and implementation of the Quintet Recruitment Intervention (QRI).

BackgroundPragmatic randomised controlled trials (RCTs) are considered essential to determine effective interventions for routine clinical practice, but many fail to recruit participants efficiently, and some really important RCTs are not undertaken because recruitment is thought to be too difficult. The ‘QuinteT Recruitment Intervention’ (QRI) aims to facilitate informed decision making by patients about RCT participation and to increase recruitment. This paper presents the development and implementation of the QRI.MethodsThe QRI developed iteratively as a complex intervention. It emerged from the National Institute for Health Research (NIHR) ProtecT trial and has been developed further in 13 RCTs. The final version of the QRI uses a combination of standard and innovative qualitative research methods with some simple quantification to understand recruitment and identify sources of difficulties.ResultsThe QRI has two major phases: understanding recruitment as it happens and then developing a plan of action to address identified difficulties and optimise informed consent in collaboration with the RCT chief investigator (CI) and the Clinical Trials Unit (CTU). The plan of action usually includes RCT-specific, as well as generic, aspects. The QRI can be used in two ways: it can be integrated into the feasibility/pilot or main phase of an RCT to prevent difficulties developing and optimise recruitment from the start, or it can be applied to an ongoing RCT experiencing recruitment shortfalls, with a view to rapidly improving recruitment and informed consent or gathering evidence to justify RCT closure.ConclusionsThe QRI provides a flexible way of understanding recruitment difficulties and producing a plan to address them while ensuring engaged and well-informed decision making by patients. It can facilitate recruitment to the most controversial and important RCTs. QRIs are likely to be of interest to the CIs and CTUs developing proposals for ‘difficult’ RCTs or for RCTs with lower than expected recruitment and to the funding bodies wishing to promote efficient recruitment in pragmatic RCTs.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1391-4) contains supplementary material, which is available to authorized users.

Critical Appraisal of Evidence for Improving Gait Speed in People with Multiple Sclerosis: Dalfampridine Versus Gait Training.

Research has not yet compared the treatment effects of dalfampridine with traditional rehabilitation of gait impairments in multiple sclerosis (MS). The purpose of this review was to critically appraise the evidence for dalfampridine and gait training for increasing gait speed in people with MS. A systematic search of the research literature was conducted. Consideration was given to only randomized controlled trials (RCTs), systematic reviews, and meta-analyses. For selection of gait training studies, only studies involving task-specific gait training interventions and measuring treatment effects on gait speed were considered. Treatment effects on gait speed were extracted from four studies examining the efficacy of dalfampridine and six gait training RCTs. Overall mean increase in gait speed with dalfampridine was 0.07 m/s (95% confidence interval [CI], 0.04-0.09 m/s) compared to 0.06 m/s (95% CI, 0.02-0.10 m/s) for gait training. Among dalfampridine responders (38% of participants in RCTs), the mean increase in gait speed was 0.16 m/s (95% CI, 0.13-0.18 m/s). Mean increases for individual gait training interventions ranged from 0.01 to 0.39 m/s; however, CIs were wide due to small sample sizes. Current evidence is insufficient to conclude whether dalfampridine or gait training is superior for improving gait speed in people with MS. These findings should be viewed cautiously due to differences in study populations and small sample sizes in gait training studies. Both treatment approaches provide only short-lived improvements. Head-to-head comparison trials and studies combining both treatment modalities are needed.

Guanfacine extended release for children and adolescents with attention-deficit/hyperactivity disorder: efficacy following prior methylphenidate treatment.

Guanfacine extended release (GXR) and atomoxetine (ATX) are nonstimulant treatments for attention-deficit/hyperactivity disorder (ADHD). As nonstimulant treatments are often used after stimulants in ADHD, GXR was assessed relative to prior stimulant treatment in a randomized controlled trial (RCT), in which ATX was included as a reference arm, and in the open-label phase of a randomized-withdrawal study (RWS). Participants were 6–17 years old with ADHD Rating Scale version IV (ADHD-RS-IV) scores ≥32 and Clinical Global Impressions – Severity scores ≥4. RCT participants received dose-optimized GXR (1–7 mg/day), ATX (10–100 mg/day), or placebo for 10–13 weeks. RWS participants received dose-optimized GXR (1–7 mg/day) for 13 weeks. Participants’ last stimulant medication prior to enrolment, and reasons for stopping this medication, were collected at baseline. Change from baseline ADHD-RS-IV score and the proportion of responders were assessed by prior stimulant exposure. Of 163 RCT and 296 RWS participants who had previously received stimulant treatment, 142 and 224, respectively, had received methylphenidate (MPH); due to the low number of participants and the heterogeneity of non-MPH treatments, we only report data for prior MPH treatment. The most frequent reasons for stopping MPH were lack of effectiveness or side effects. Placebo-adjusted ADHD-RS-IV changes from baseline were significant in participants receiving GXR (prior MPH, −9.8, P<0.001, effect size [ES] 0.85; stimulant-naïve, −7.6, P<0.001, ES 0.65). In ATX-treated participants, significant placebo-adjusted differences were seen in stimulant-naïve (−5.0, P=0.022, ES 0.43) but not prior MPH-treated (−1.8, P>0.05, ES 0.15) participants. More participants met responder criteria with GXR versus placebo, regardless of prior treatment. GXR response was unaffected by prior stimulant treatment; ATX produced improvement only in stimulant-naïve participants relative to placebo. These findings may be relevant to clinical decision-making regarding sequencing of ADHD treatments.

Evaluating cognitive effort in a randomized controlled trial.

Many randomized controlled trials (RCTs) of neuropsychiatric conditions involve cognitive outcome measures; however, validity of cognitive data relies on adequate effort during testing, and such screening is seldom performed. Given well-established rates of 10 to 30% poor effort in clinical settings, this is not a trivial concern. This preliminary study evaluated effort during cognitive testing in an RCT of omega-3 supplementation to reduce suicidality in a high-risk psychiatric population. An interim analysis of sustained attentions measures from the Connors Performance Test (CPT-2) at baseline for the first 60 participants was conducted. Previously validated cut points to detect insufficient effort on the CPT-2 were applied. At baseline, 12% (7) were identified as giving poor effort. Follow-up analyses indicated less psychiatric distress and suicidality among those who gave poor effort. Results suggest comparable likelihood of a poor effort on cognitive testing in clinical and RCT participation. Reduced psychiatric distress in the poor effort group raises concern regarding interpretation of other measures. The importance of screening cognitive data for effort in RCTs is highlighted. Future studies will examine effort at follow-up visits, and explore relationships to attrition, adherence, and response to treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Assessing sample representativeness in randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network.

To compare the characteristics of individuals participating in randomized controlled trials (RCTs) of treatments of substance use disorder (SUD) with individuals receiving treatment in usual care settings, and to provide a summary quantitative measure of differences between characteristics of these two groups of individuals using propensity score methods. Design Analyses using data from RCT samples from the National Institute of Drug Abuse Clinical Trials Network (CTN) and target populations of patients drawn from the Treatment Episodes Data Set-Admissions (TEDS-A). Settings Multiple clinical trial sites and nation-wide usual SUD treatment settings in the United States. A total of 3592 individuals from 10 CTN samples and 1602226 individuals selected from TEDS-A between 2001 and 2009. Measurements The propensity scores for enrolling in the RCTs were computed based on the following nine observable characteristics: sex, race/ethnicity, age, education, employment status, marital status, admission to treatment through criminal justice, intravenous drug use and the number of prior treatments. Findings The proportion of those with ≥12years of education and the proportion of those who had full-time jobs were significantly higher among RCT samples than among target populations (in seven and nine trials, respectively, at P<0.001). The pooled difference in the mean propensity scores between the RCTs and the target population was 1.54 standard deviations and was statistically significant at P<0.001. In the United States, individuals recruited into randomized controlled trials of substance use disorder treatments appear to be very different from individuals receiving treatment in usual care settings. Notably, RCT participants tend to have more years of education and a greater likelihood of full-time work compared with people receiving care in usual care settings.

Abstract P4-11-09: A randomized controlled trial of postoperative adjuvant therapy for elderly breast cancer patients: Comparison of health-related quality of life between clinical trial participants and decliners

Abstract Background: Health-related quality of life (HRQoL) is one of the important outcomes in cancer control trials and has increasingly become the one of the primary foci. Obtaining informed consent from participants is essential for participation in randomized controlled trials (RCTs), but the participation in these RCTs may directly influence HRQoL, because treatment options are determined according to the allocation schedule. To date, only a few studies have compared HRQoL between clinical trial participants and decliners. Patients and Method: The National Surgical Adjuvant Study of Breast Cancer 07 (N-SAS BC 07) is a randomized controlled trial in women with HER2-positive primary breast cancer who are over 70 years of age. The primary aim was to investigate the benefit of trastuzumab monotherapy compared with combination therapy using trastuzumab and chemotherapy. The study concept and design were published in concept paper (Sawaki M. et al., Jpn J Clin Oncol. 2011). In this study, patients were randomized to receive either trastuzumab plus chemotherapy or trastuzumab monotherapy. The primary endpoint was disease-free survival, and the secondary endpoints were overall survival, relapse-free survival, safety, HRQoL, comprehensive geriatric assessment (CGA) and cost effectiveness (protocol ID; NCT01104935). HRQoL and CGA were assessed at registration (baseline), 2 month, 1 year, and 3 years after the start of protocol treatments using the Functional Assessment of Cancer Therapy-General (FACT-G), Hospital Anxiety and Depression Scale (HADS), EuroQol 5 Dimension (EQ-5D), Tokyo Metropolitan Institute of Gerontology (TMIG) index of competence, and the Philadelphia Geriatric Center (PGC) Morale Scale. The patients who declined to participate in N-SAS BC 07 were registered in a cohort study to prospectively evaluate the subsequent treatment options and prognosis (07-Cohort). The same questionnaire that was used in N-SAS BC 07 was used in 07-Cohort to evaluate HRQoL and CGA at entry. Results: Patients were enrolled from October 2012 to October 2016. During this period, 275 and 123 patients were registered in N-SAS BC 07 and 07-Cohort, respectively. The mean age at entry of the patients in the N-SAS BC 07 and 07-Cohort groups was 73.9 and 74.6 years, respectively. The questionnaire response rates at baseline in the patients in N-SAS BC 07 and 07-Cohort groups were 89% and 82%, respectively. There were no significant differences in FACT-G, HADS, EQ-5D, or TMIG index of competence at baseline between the groups, but the mean (standard deviation) scores of PGC Morale Scale in N-SAS BC 07 and 07-Cohort groups were 10.8 (3.3) and 9.9 (3.7), respectively, with the scores being significantly greater in the N-SAS BC 07 group (p=0.020, t-test). Conclusion: The PGC Morale Scale provides a multidimensional approach to assess the psychological state of older people. This study indicated that participation in the RCT did not affect the baseline QoL of elderly patients but suggested that the baseline QoL of the RCT participants was better than decliners. Citation Format: Saito T, Sawaki M, Hozumi Y, Sagawa N, Iwata H, Kashiwaba M, Kawashima H, Kobayashi K, Taira N, Takashima T, Takahashi M, Tsuneizumi M, Nakayama T, Baba S, Bando H, Mizuno T, Yamaguchi M, Yamamoto Y, Uemura Y, Ohashi Y, Mukai H. A randomized controlled trial of postoperative adjuvant therapy for elderly breast cancer patients: Comparison of health-related quality of life between clinical trial participants and decliners. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-09.

The value of surrogate endpoints for predicting real-world survival across five cancer types

Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints – progression-free survival (PFS) and time to progression (TTP) – to predict real-world OS across five cancers.Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan–Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991–2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R2 from linear regressions.Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P = 0.026). Among all real-world patients using sample treatments (N = 309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P = 0.194). Results were qualitatively similar using median absolute prediction error and R2 metrics.Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone.

The feasibility and acceptability of using the Mother-Generated Index (MGI) as a Patient Reported Outcome Measure in a randomised controlled trial of maternity care.

BackgroundUsing patient-reported outcome measures (PROMs) to assess Quality of Life (QoL) is well established, but commonly-used PROM item-sets do not necessarily capture what all respondents consider important. Measuring complex constructs is particularly difficult in randomised controlled trials (RCTs). The Mother-Generated Index (MGI) is a validated antenatal and postnatal QoL instrument in which the variables and scores are completely respondent-driven. This paper reports on the feasibility and acceptability of the MGI in an RCT, and compares the resulting variables and QoL scores with more commonly used instruments.MethodsThe single-page MGI was included at the end of a ten page questionnaire pack and posted to the RCT participants at baseline (28–32 weeks’ gestation) and follow-up (six weeks postnatal). Feasibility and acceptability were assessed by ease of administration, data entry and completion rates. Variables cited by women were analysed thematically. MGI QoL scores were compared with outcomes from the EQ-5D-3 L; Edinburgh Postnatal Depression Scale; Satisfaction With Life Scale; and State Trait Anxiety Inventory.ResultsSix hundred and seventy eight pregnant women returned the pack at baseline; 668 completed the MGI (98.5 %); 383/400 returns at follow up included a completed MGI (95.7 %). Quantitative data were scanned into SPSS using a standard data scanning system, and were largely error-free; qualitative data were entered manually. The variables recorded by participants on the MGI forms incorporated many of those in the comparison instruments, and other outcomes commonly used in intrapartum trials, but they also revealed a wider range of issues affecting their quality of life. These included financial and work-related worries; moving house; and concerns over family illness and pets. The MGI scores demonstrated low-to-moderate correlation with other tools (all r values p < .01).ConclusionsWithout face-to-face explanation and at the end of a long questionnaire, the MGI was feasible to use, and acceptable to RCT participants. It allowed individual participants to include issues that were important to them, but which are not well captured by existing tools. The MGI unites the explanatory power of qualitative research with the comparative power of quantitative designs, is inexpensive to administer, and requires minimal linguistic and conceptual translation.Trial registrationISRCTN27575146 (date assigned 23 March 2011)

Do Patients at Sites With High RCT Enrollment Propensity Have Better Outcomes?

Concerns about randomized controlled trial (RCT) generalizability typically center on characteristics of RCT patient participants. Possibly there are RCT site characteristics that distinguish RCT outcomes from those that can be expected in non-RCT settings. To examine whether site propensity toward RCT enrollment is associated with recovery outcomes for patients and whether the association differs between patients who participate in a RCT compared with those who remain in an observational (OBS) treatment environment. Study participants with acute bipolar depression from The Systematic Treatment Enhancing Program for Bipolar Disorder acute depression pharmacotherapy RCT (N=337) and OBS treatment arm (N=1581). A longitudinal OBS study comparing the likelihood of recovery in the RCT to the OBS arm, allowing effect modification by site high RCT enrollment propensity (defined as >the median) and other predictors over a 6-month follow-up period. Non-RCT participants who received care in sites with high RCT enrollment propensity had a higher probability of recovering from their bipolar-depression episode compared with participants from low propensity sites [odds ratio (95% confidence interval)=2.13 (1.28-3.55)]. RCT enrollment propensity was not associated with recovery outcomes for RCT participants [1.03 (0.35-3.03)]. Sites with high propensity to enroll patients in RCTs appear to have unobserved characteristics, which play a significant role in outcomes for non-RCT patients. For RCT participants in low-enrollment sites, possibly RCT protocols, which proscribe care delivery and monitoring, attenuate this effect. These results have implications for future research to improve outcomes in nonresearch care settings.

Linezolid for Treating Tuberculosis: A Delicate Balancing Act

Linezolid for Treating Tuberculosis: A Delicate Balancing Act

Barriers to participation in surgical randomized controlled trials in pediatric urology: A qualitative study of key stakeholder perspectives

Randomized controlled trials (RCTs) are considered the gold standard for assessing treatment efficacy. However, pediatric surgical RCTs have been limited in their ability to recruit patients. The purpose of this study was to identify barriers and motivators to pediatric participation in surgical RCTs. We conducted a series of two focus groups with parents and one focus group with urology providers for children aged <2 years of age with a diagnosis of Society for Fetal Urology grade 3 or 4 hydronephrosis. We then administered a survey to referring pediatricians based on the initial analysis of focus group findings. Theme analysis was used for all qualitative transcribed text data obtained from focus groups and open-ended survey questions using team-based inductive approaches. Descriptive statistics were obtained for the remainder of the provider survey. Using qualitative text from stakeholders (n=38) we identified four key themes across the data: responsibility to my child; responsibility to my patient; responsibility to the field; and irreversibility of surgery. Participants felt there was an obligation to be informed of relevant scientific research within a clinic research culture. However, there remains a disconnect for parents between randomized research studies that may ultimately benefit their child, depending on their age and concern their child is being treated as a 'guinea pig'. Some parents were willing to participate in RCTs but all were more open to participate in an observational study where the treatment decisions were felt to be under their control even when there was no "right answer" or multiple equivalent options for treatment. There was mixed opinion across the parents and providers whether research trial education and enrollment should be provided by the pediatrician or urologist. Active physician decisions were seen as critical within the context of a long term clinical relationship and provision of information of risks and benefits without pressure were considered essential for ethical research by both parents and providers. While some parents are open to participation in surgical RCTs, providers and parents of children with hydronephrosis feel discomfort with the element of chance in surgical randomized trials. Parents and providers are more likely to participate in observational studies where treatment decisions may be made jointly by the physician and the parent. These findings suggest that pragmatic trial strategies with the option for participation in an observational cohort may improve recruitment of pediatric patients into surgical clinical trials.

Recruitment strategies and patient selection in clinical trials for Parkinson's disease: Going viral and keeping science and ethics at the highest standards.

Enrollment of an adequate number of suitable candidates is a critical component of good quality randomized controlled trials (RCTs). Parkinson's disease (PD) is a highly heterogeneous disease and recruiting a large and homogeneous sample of patients is often challenging. Further, PD patients are often elderly, cognitively impaired and disabled, thus requiring the assistance from their caregivers for participation in RCTs. Only a limited number of studies have explored the effectiveness of recruitment strategies and PD patient selection in clinical trials. We aim to review the four crucial recruitment components of RCTs (i.e. infrastructure, nature of the research, recruiter characteristics and participant characteristics) with particular implications in PD, and to explore strategies to improve recruitment and patient selection in RCTs in PD. Movement disorders centers have a key role in managing recruitment and patient selection in RCTs in PD. Key recommendations within the infrastructure component are to improve trust and communication between patient and participant, and to consider the diversity, perceived disadvantages, and health care accessibility of the participants. Further, study designs that involve participant's opinions and considers placebo and lessebo effects are highly recommended for the nature of the research component of RCTs. Finally, a team-based approach with recruiters and participants that establishes relationships between researchers and the community and addresses ethical considerations are encouraged as part of the recruiters and participants components. Finally, we envisage a greater usage of internet-based strategies for clinical trials recruitment in PD with the goal of 'going viral' with the recruitment.