Ethical aspects of clinical trials: the attitudes of participants in two non-cancer trials

OBJECTIVES: To investigate attitudes to clinical trials in non-cancer trial participants. DESIGN: Questionnaires at entry, during, and after participation in a clinical study. SETTING: Participants in: (i) ROC: a clinical study comparing systemic interferon-alpha-2A treatment vs. prednisolone enemas in ulcerative colitis; and (ii) MRCRUC: a clinical study investigating low-field magnetic resonance imaging as a new modality for the evaluation of patients with inflammatory bowel disease. SUBJECTS: Thirty-two patients in ROC and 47 patients in MRCRUC. OUTCOME MEASURES: Attitudes towards different aspects of clinical research. RESULTS: The majority found scientific testing of clinical methods necessary, having positive attitudes towards both participation by themselves and others. The creation of a personal moral problem by denying participation was rejected by a large majority, and still both personal and altruistic motives for participation were highly rated. An important motive for accepting inclusion was the expectation of being 'a special patient' during the trial. The presence of research ethics committees controlling clinical research had a significant positive impact on decisions to participate, and drawing lots and blinding were found problematic by only a minority. Patients valued their satisfaction with participation in the trials highly, and would almost all accept a request to participate in future trials. The most important reason for this was a feeling of receiving better care and information than expected outside a trial setting, primarily determined by the patients seeing only one physician during the trials. A pronounced wish to obtain follow-up information was expressed. CONCLUSION: Attitudes towards medical research are positive with both altruistic and nonaltruistic motives for participation. Expectations of being treated as 'a special patient' in the trial were important in accepting to participate. Seeing the same physician at control visits was an important factor for satisfaction with participation.     

Ethical aspects of clinical trials: the attitudes of the public and out-patients

OBJECTIVES: To investigate attitudes to clinical research amongst potential research participants. DESIGN: Questionnaire-survey. SETTING: Two medical out-patient clinics and the background population. SUBJECTS: A total of 508 randomly selected citizens in Copenhagen County (64% responded) and 200 consecutive patients attending the out-patient clinics (64% responded). OUTCOME MEASURES: Attitudes toward different aspects of clinical research. RESULTS: Positive attitudes toward medical research were disclosed. The majority found scientific testing necessary, although only a minority considered participation a moral obligation. Both personal benefits and altruistic motives for participation were highly rated, whereas former positive experiences from trial participation had only minor impact on decisions. Several respondents stated former trial participation had changed their attitudes negatively. Lack of feedback of results was of major importance for this change. Attitudes are significantly influenced by the presence of independent research ethics committees, whereas trial technicalities such as drawing lots and blinding was found problematic by only a few respondents. Altruistic motives of physicians to conduct trials were highly rated by a majority of respondents, but the motive of promoting doctors' careers was also judged important. Respondents rated nondiscomforting procedures as acceptable or having only a small impact or strain on their lives. CONCLUSION: Attitudes toward medical research are positive amongst out-patients and the general public. Altruistic and nonaltruistic motives both concerning trial participation and concerning the motives of physicians to conduct medical research were rated highly. Lack of feedback concerning results of trials to participants was important for a negative change in attitude toward participation.     

Japan's contribution to clinical research in gastroenterology and hepatology

Background. Although Japan's contributions to several biomedical fields have already been reported, little is known about Japan's contribution to gastroenterology and hepatology. Methods. Original articles published in 1991 through 2000 in highly reputed journals in the field of gastroenterology and hepatology were retrieved from the MEDLINE database. The number of articles having an affiliation with a Japanese institution was counted in total, and the number for each journal was also counted. Japan's share of articles regarding clinical trials and randomized controlled trials (RCTs) in this field was also determined, along with the trend over the past decade. Results. Japan's share of articles in this field was 10.6%, ranking third in the world, following the United States (35.1%) and the United Kingdom (11.5%). Japan's share of articles went up significantly as a whole (P = 0.01), while the share for RCTs showed no significant change (P = 0.57) during this period of time. Conclusions. Japan's contribution to the field of gastroenterology and hepatology is, in general, acceptable compared with that of other counties, but the contribution for RCTs not satisfactory.     

Enhancing the validity and utility of randomized clinical trials in addictions treatment research: II. Participant samples and assessment

PURPOSE: This paper is the second in a series that describes strategies for optimizing the validity and utility of randomized clinical trials (RCTs) in addictions treatment research. Whereas the first paper focused on treatment implementation and research design, here we address issues pertaining to participant samples and assessment methods. SCOPE: With respect to participant samples, sections focus on the definition of study populations; informed consent; sample size and statistical power; recruitment and enrollment; sample retention; and participant tracking systems. Assessment topics include eligibility screening and baseline assessment; treatment-related variables; outcome measures; the frequency of follow-up evaluation; and assessment process. A final section highlights the importance of pilot testing. CONCLUSIONS: Sample recruitment and retention strategies are needed that safeguard both internal and external validity. Daily estimation assessment procedures are recommended because of their versatility for creating a range of outcome measures. Assessment batteries should include measures that permit the investigation of treatment processes and mechanisms of action.     

Asthma research and randomized controlled trials: a remarkable phenomenon

Background. Time trends in the number of publications of randomized controlled trials (RCTs) in asthma research have never been evaluated. Methods. A PubMed database scan was made to identify publications in asthma research per year since 1990 until 1 January 2010, using the term ‘asthma’. The total number of publications was ascertained, as was the number when restricting the search strategy to RCTs only. Results. The total number of publications in asthma research increased from 2240 per year in 1990 to 5601 per year in 2009. The number of publications of RCTs in asthma research was 198 per year in 1990 and 233 per year in 2009. Discussion. The remarkable phenomenon of an almost unchanged number of publications of RCTs in asthma research per year in the period 1990-2009 may be explained by criticism to RCTs in asthma research. Conclusion. Despite an increase in total publications of asthma research, time trends in the number of publications of RCTs in asthma research per year show an almost unchanged number in the period 1990-2009. Evidence-based medicine within the field of asthma still faces many challenges.     

Effect of student involvement on patient perceptions of ambulatory care visits: a randomized controlled trial

OBJECTIVE: To determine if patient satisfaction with ambulatory care visits differs when medical students participate in the visit. DESIGN: Randomized controlled trial. SETTING: Academic general internal medicine practice. PARTICIPANTS: Outpatients randomly assigned to see an attending physician only (N = 66) or an attending physician plus medical student (N = 68). MEASUREMENTS AND MAIN RESULTS: Patient perceptions of the office visit were determined by telephone survey. Overall office visit satisfaction was higher for the "attending physician only" group (61% vs 48% excellent), although this was not statistically significant (P =.16). There was no difference between the study groups for patient ratings of their physician overall (80% vs 85% excellent; P =.44). In subsidiary analyses, patients who rated their attending physician as "excellent" rated the overall office visit significantly higher in the "attending physician only" group (74% vs 55%; P =.04). Among patients in the "attending physician plus medical student" group, 40% indicated that medical student involvement "probably" or "definitely" did not improve their care, and 30% responded that they "probably" or "definitely" did not want to see a student at subsequent office visits. CONCLUSIONS: Although our sample size was small, we found no significant decrement in patient ratings of office visit satisfaction from medical student involvement in a global satisfaction survey. However, a significant number of patients expressed discontent with student involvement in the visit when asked directly. Global assessment of patient satisfaction may lack sensitivity for detection of dissatisfaction. Future research in this area should employ more sensitive measures of patient satisfaction.     

Enhancing the validity and utility of randomized clinical trials in addictions treatment research: I. Treatment implementation and research design

PURPOSE: This paper is the first in a series that examines methods for improving the validity and utility of randomized clinical trials (RCTs) in addictions treatment research. The specific foci of this article are treatment implementation and research design. SCOPE: We begin by considering the conditions under which the RCT provides an appropriate design choice. Sections that follow discuss methodological issues with respect to RCT structure and collaborative arrangements; treatment specification, delivery and cost; experimental design; and randomization/blinding procedures. We emphasize the importance of advance planning; treatment integrity and discriminability; treatment standardization; staff training and supervision; client compliance; maintenance of between-group equivalence across study conditions; and inclusion of appropriate comparison groups in study designs. CONCLUSIONS: Investigators are encouraged to maximize the internal validity of RCTs, but also to consider methods for enhancing external validity. The utility of addictions RCTs for advancing theory and improving clinical practice can be enhanced by investigating underlying mechanisms of action.     

A Population‐Based Osteoporosis Screening Program: Who Does Not Participate,and What Are the Consequences?

OBJECTIVES: To describe differences in osteoporosis risk factors and rates of fracture and antiresorptive therapy use in women who did and did not participate in an osteoporosis screening program. SETTING: Group Health Cooperative, a health maintenance organization in western Washington state. PARTICIPANTS: A total of 9,268 women (aged 60-80) who were not using any antiresorptive therapy were invited to participate in an osteoporosis screening program. This study compares the 35% who participated with the 65% who did not. DESIGN: This observational cohort study of women invited to participate in a randomized, controlled trial of an osteoporosis screening program provided all participants with personalized feedback on their risk of osteoporosis. Some participants also received bone density testing. Automated administrative data were used to examine differences between participants and nonparticipants in fracture outcomes and medication initiation before and after invitation. RESULTS: Baseline fracture rates did not differ between participants and nonparticipants. After age adjustment, nonparticipants had a higher hip fracture rate (14.1 vs 8.3 per 1,000) and a lower rate of initiating any antiresorptive therapy (10.3 vs 17.9 per 100) than participants after an average of 28 to 29 months of follow-up. CONCLUSION: Participants had reduced hip fracture rates and increased initiation of antiresorptive therapy compared with nonparticipants. It was not possible to determine whether participating in the screening program, unmeasured confounding, or selection bias accounted for differences in hip fracture or therapy initiation rates. These results suggest that women who do not participate in osteoporosis screening should be pursued to identify individuals who could benefit from primary and secondary osteoporosis prevention.     

HIV-Infected African Americans are Willing to Participate in HIV Treatment Trials

Background Despite the high prevalence rates of HIV infection in the African-American community, African Americans remain underrepresented in HIV treatment trials. Objective (1) To develop a questionnaire that measures attitudes and concerns about HIV treatment trials among HIV-infected African Americans at a university-based clinic. (2) To determine actual participation rates and willingness to participate in future HIV treatment trials among HIV-infected African Americans at a university-based clinic. Design Questionnaire development and cross-sectional survey. Setting, Participants, and Measurements In a sample of 200 HIV-infected African-American adults receiving medical care at the Pittsburgh AIDS Center for Treatment (a university-based ambulatory clinic), we assessed research participation rates and willingness to participate in future HIV treatment trials, trust in the medical profession, sociodemographic characteristics, attitudes, and concerns about HIV treatment trials. Main Outcome Measures Research participation rates and willingness to participate in future HIV treatment trials. Results Only 57% of survey respondents had ever been asked to participate in an HIV treatment trial but 86% of those asked said yes. Prior research participation was significantly related to willingness to participate in future HIV treatment trials (P = .001). Contrary to previous studies, neither trust/distrust in the medical profession nor beliefs about the dishonesty of researchers was associated with research participation rates or willingness to participate in future HIV treatment trials. Conclusions Having never been asked to participate in research is a major barrier to the participation of HIV-infected African Americans in HIV treatment trials. African Americans who seek medical care for HIV infection should be asked to participate in HIV treatment trials.     

Training Residents to Employ Self-efficacy-enhancing Interviewing Techniques: Randomized Controlled Trial of a Standardized Patient Intervention

Background  Current interventions to enhance patient self-efficacy, a key mediator of health behavior, have limited primary care application. Objective  To explore the effectiveness of an office-based intervention for training resident physicians to use self-efficacy-enhancing interviewing techniques (SEE IT). Design  Randomized controlled trial. Participants  Family medicine and internal medicine resident physicians (N = 64) at an academic medical center. Measurements  Resident use of SEE IT (a count of ten possible behaviors) was coded from audio recordings of the physician-patient portion of two standardized patient (SP) instructor training visits and two unannounced post-training SP visits, all involving common physical and mental health conditions and behavior change issues. One post-training SP visit involved health conditions similar to those experienced in training, while the other involved new conditions. Results  Experimental group residents demonstrated significantly greater use of SEE IT than controls, starting after the first training visit and sustained through the final post-training visit. The mean effect of the intervention was significant [adjusted incidence rate ratio for increased use of SEE IT = 1.94 (95% confidence interval = 1.34, 2.79; p < 0.001)]. There were no significant effects of resident gender, race/ethnicity, specialty, training level, or SP health conditions. Conclusions  SP instructors can teach resident physicians to apply SEE IT during SP office visits, and the effects extend to health conditions beyond those used for training. Future studies should explore the effects of the intervention on practicing physicians, physician use of SEE IT during actual patient visits, and its influence on patient health behaviors and outcomes.     

Assessment by human research ethics committees of potential conflicts of interest arising from pharmaceutical sponsorship of clinical research

Background: Conflicts of interest arising from pharmaceutical industry sponsorship of clinical research have the potential to bias research outcomes and ultimately prejudice patient care. It is unknown how Australian Human Research Ethics Committees (HREC) assess and manage such conflicts of interest. We aimed to gain an understanding of how HREC approach the problem of potential conflicts of interest arising from pharmaceutical sponsorship of clinical research. Method: We conducted a survey of HREC chairpersons in New South Wales. Results: HREC vary widely in their approaches to conflicts of interest, including in their use of National Health and Medical Research Council guidelines, which were often misinterpreted or overlooked. Many committees rely primarily on researchers disclosing potential conflicts of interest, whereas a majority of HREC use disclosure to research participants as the primary tool for preventing and managing conflicts of interest. Almost no HREC place limitations on researcher relationships with pharmaceutical companies. Conclusion: These findings suggest reluctance on the part of HREC to regulate many potential conflicts of interest between researchers and pharmaceutical sponsors, which may arise from uncertainty regarding the meaning or significance of conflicts of interest in research, from ambiguity surrounding the role of HREC in assessing and managing conflicts of interest in research or from misinterpretation or ignorance of current National Health and Medical Research Council guidelines. Further review of policies and practices in this important area may prove beneficial in safeguarding clinical research and patient care while promoting continuing constructive engagement with the pharmaceutical industry.     

Comparison of registered and published primary outcomes in randomized controlled trials of gastroenterology and hepatology

Abstract

Objectives. The need for trial registration as well as the benefits it has brought for the transparency of medical research has been recognized for years. Trial registration has turned from an exception to a mandatory guideline in recent years. The present study aimed to examine the characteristics of registered randomized controlled trials (RCTs) in a sample of recently published gastroenterology RCTs, and to assess the consistency of registered and published primary outcome (PO) in RCTs. Methods. Articles published in the top five “general and internal journals” and top five “gastroenterology and hepatology journals” categories between 2009 and 2012 were searched in PubMed. Basic characteristics and the registration information were identified and extracted from the included RCTs. PO consistency analysis was conducted to compare between the registered and published format. Results. A total of 305 RCTs were included; among them 252 could be identified with a registration number. Nearly half of these RCTs were funded solely by industry (141/305, 46.3%). ClinicalTrials.gov was the most popular registry for these RCTs (214/252, 84.9%). A total of 155 RCTs were included in the PO consistency analysis. Among them, 22 (14.2%) RCTs had discrepancies between POs registered in the trial registry compared to the published article. Conclusions. Based on the results of the present study, selective outcome reporting of gastroenterology RCTs published in leading medical journals has been much improved over the past years. However, there might be a sampling bias to say that consistency of registered and published POs of gastroenterology RCTs has been better than before.     

Enhancing the validity and utility of randomized clinical trials in addictions treatment research: III. Data processing and statistical analysis

PURPOSE: This is the third paper in a series that reviews strategies for optimizing the validity and utility of randomized clinical trials (RCTs) in addictions treatment research. Whereas the two previous papers focused on design and implementation, here we address issues pertaining to data processing and statistical analysis. SCOPE: Recommendations for enhancing data quality and utility are offered in sections on data coding and entry; and data format, structure and management. We discuss the need for preliminary data analyses that examine statistical power; patterns of attrition; between-group equivalence; and treatment integrity and discriminability. We discuss tests of treatment efficacy, as well as ancillary analyses aimed at explicating treatment processes. CONCLUSIONS: Safeguards are necessary to protect data quality, and advance planning is needed to ensure that data formats are compatible with statistical objectives. In addition to treatment efficacy, statistical analyses should evaluate study internal and external validity, and investigate the change mechanisms that underlie treatment effects.     

Efficacy and safety of community-based moxibustion for primary hypertension: A randomized controlled trial with patient preference arms

Moxibustion has been shown to have a potential antihypertensive effect, but its applicability for the primary care of hypertension is unclear. The authors conducted a multicenter randomized controlled trial (RCT) with patient preference arms to investigate the effect, safety, cost-effectiveness, and compliance of moxibustion in community patients with hypertension. Patients with primary hypertension were enrolled from seven communities randomly or nonrandomly assigned to receive self-administered moxibustion + the original hypertensive regimen or the original hypertensive regimen alone for 6 months. The authors mainly evaluated the effects of moxibustion on hypertensive outcomes and adverse events. As a result, a total of 160 and 240 patients were recruited into the randomized and nonrandomized arms, respectively, with 87.5% completing the follow-up. At month 6, there was a significantly greater reduction in systolic blood pressure (SBP) (difference: −10.57 mmHg), a higher proportion of responders (82.2% vs. 53.7%; odds ratio 4.00), and better improvements in hypertensive symptoms and quality of life (QoL) in the moxibustion group than in the control group in the randomized population, but there was no significant between-group difference in diastolic blood pressure (DBP). The nonrandomized findings showed the same effect direction for all outcomes, except for DBP. All moxibustion-related adverse events were mild. In conclusion, moxibustion can reduce SBP and improve hypertensive symptoms and QoL in community patients with hypertension, with good safety and low cost, although its effect on DBP remains uncertain. The findings suggest that moxibustion may be an appropriate technique for community primary care of hypertension.     

A randomized trial of teaching clinical skills using virtual and live standardized patients

BACKGROUND: We developed computer-based virtual patient (VP) cases to complement an interactive continuing medical education (CME) course that emphasizes skills practice using standardized patients (SP). Virtual patient simulations have the significant advantages of requiring fewer personnel and resources, being accessible at any time, and being highly standardized. Little is known about the educational effectiveness of these new resources. We conducted a randomized trial to assess the educational effectiveness of VPs and SPs in teaching clinical skills. OBJECTIVE: To determine the effectiveness of VP cases when compared with live SP cases in improving clinical skills and knowledge. DESIGN: Randomized trial. PARTICIPANTS: Fifty-five health care providers (registered nurses 45%, physicians 15%, other provider types 40%) who attended a CME program. INTERVENTIONS: Participants were randomized to receive either 4 live cases (n=32) or 2 live and 2 virtual cases (n=23). Other aspects of the course were identical for both groups. RESULTS: Participants in both groups were equivalent with respect to pre-post workshop improvement in comfort level (P=.66) and preparedness to respond (P=.61), to screen (P=.79), and to care (P=.055) for patients using the skills taught. There was no difference in subjective ratings of effectiveness of the VPs and SPs by participants who experienced both (P=.79). Improvement in diagnostic abilities were equivalent in groups who experienced cases either live or virtually. CONCLUSIONS: Improvements in performance and diagnostic ability were equivalent between the groups and participants rated VP and SP cases equally. Including well-designed VPs has a potentially powerful and efficient place in clinical skills training for practicing health care workers.