Study design factors influencing patients' willingness to participate in clinical research: a randomised vignette-based study.

BACKGROUND: High patient participation in clinical research reduces selection bias and ensures the generalizability of study findings. We explored study-related factors that may influence patients' willingness to participate in research. METHODS: We submitted by mail two vignettes that described clinical research studies - a drug trial and a diagnostic study - to patients recently discharged from hospital and assessed their willingness to participate. We used a factorial design to randomly allocate three study attributes per vignette: in the drug trial, presumed superiority of new drug versus equipoise, public versus industry funding, and random versus non-random treatment allocation; in the diagnostic study, common versus rare disease, genetic versus protein analysis, and automatic reporting of results versus reporting on request. RESULTS: Of 2600 patients contacted, 1140 (44%) participated. Globally, willingness to participate in a drug trial was lower than in a diagnostic study (44.8% vs. 76.2%; P < 0.001). In the drug trial, participation was significantly higher when the new drug was presented as presumably better than the old (vs. equipoise) and when the study was funded by public sources (vs. industry), but was not affected by the allocation method. None of the factors tested in the diagnostic study was associated with participation. CONCLUSIONS: Patients were more likely to participate in a hypothetical observational diagnostic study than in a hypothetical drug trial. Participation in the trial was lower when clinical equipoise was expressed and when the trial was funded by industry. These results suggest that some features of study design can influence participation.

Biobank attributes associated with higher patient participation: a randomized study.

The objectives of the study were to assess patients' intent to participate in a hospital-based biobank and to explore the factors associated with higher participation. A 23-item questionnaire was developed to survey a random sample of patients in a Swiss university hospital. Two vignettes describing hypothetical biobanks were incorporated in the survey and patients were asked whether they would agree to participate. Three factors were randomly manipulated in each vignette using a factorial design: cancer-oriented research vs general consent, one vs several reviews of the patient's chart, and genetic vs blood protein analyses (first vignette); blood sample vs oral swabbing, local vs international project, and a follow-up visit vs no visit (second vignette). Of the 1140 respondents, 73.6 and 69.6%, respectively, agreed to participate in the biobank. Biospecimen collection via oral swabbing, single chart review, and no follow-up were associated with higher participation. Participation was also higher among younger patients, Europeans, patients who had a positive opinion on research, and blood/organ donors. Biobanking was supported by a majority of patients, especially if biospecimens were collected through non-invasive techniques or if data collection was done once. The scope of consent, the scale of the project, or the tests performed on biospecimens did not influence participation.

How do researchers determine the difference to be detected in superiority trials? Results of a survey from a panel of researchers.

BACKGROUND: There is currently no guidance for selecting a specific difference to be detected in a superiority trial. We explored 3 factors that in our opinion should influence the difference to be detected (type of outcome, patient age group, and presence of treatment side-effects), and 3 that should not (baseline level of risk, logistical difficulties, and cost of treatment). METHODS: We conducted an experimental survey using a factorial design among 380 corresponding authors of randomized controlled trials indexed in Medline. Two hypothetical vignettes were submitted to participants: one described a trial of a new analgesic in mild trauma injuries, the other described a trial of a new chemotherapy among cancer patients. The first vignette tested the baseline level of risk, patient age-group, patient recruitment difficulties, and treatment side-effects. The second tested the baseline level of risk, patient age-group, type of outcome, and cost of treatment. The respondents were asked to select the smallest gain of effectiveness that should be detected by the trial. RESULTS: In vignette 1, respondents selected a median difference to be detected corresponding to an improvement of 7.0 % in pain control with the new treatment. In vignette 2, they selected a median difference to be detected corresponding to a reduction of 5.0 % in mortality or cancer recurrence with the new chemotherapy. In both vignettes, the difference to be detected decreased significantly with the baseline risk. The other factor influencing difference to be detected was the age group, but the impact of this factor was smaller. Cost, side-effects, outcome severity, or mention of logistical difficulties did not significantly impact the difference to be detected selected by participants. CONCLUSIONS: Three of the anticipated effects conformed to our expectations (the effect of patient age, and absence of effect of the cost of treatment and of patient recruitment difficulties) and the other three did not. These findings can guide future research in determining differences to be detected in trials that can translate to meaningful clinical decision-making.

Patient enrollment and logistical problems top the list of difficulties in clinical research: a cross-sectional survey.

BACKGROUND: Many medical research projects encounter difficulties. The objective of this study was to assess the self-reported frequency of difficulties encountered by medical researchers while conducting research and to identify factors associated with their occurrence. METHODS: The authors conducted a cross-sectional survey in 2010 among principal investigators of 996 study protocols approved by the Research Ethics Committee in Geneva, Switzerland, between 2001 and 2005. The authors asked principal investigators to rate the level of difficulty (1: none, to 5: very great) encountered across the research process. RESULTS: 588 questionnaires were sent back (participation rate 59.0 %). 391 (66.5 %) studies were completed at the time of the survey. Investigators reported that the most frequent difficulties were related to patient enrollment (44.3 %), data collection (26.7 %), data analysis and interpretation (21.5 %), collaboration with caregivers (21.0 %), study design (20.4 %), publication in peer-reviewed journal (20.2 %), hiring of competent study personnel (20.2 %), and getting funding (19.2 %). On average, investigators reported 2.8 difficulties per project (SD 2.8, range 0 to 12). In multivariable analysis, the number of difficulties was higher for studies initiated by public sponsors (vs. private), single center studies (vs. multicenter), and studies about treatment, diagnosis or prognosis (i.e., clinical vs. other studies). CONCLUSIONS: Medical researchers reported substantial logistical difficulties in conducting clinical research.

The choice of the noninferiority margin in clinical trials was driven by baseline risk, type of primary outcome, and benefits of new treatment.

OBJECTIVES: To explore characteristics of clinical trials that influence the choice of the noninferiority margin (NIM) when planning the trial. STUDY DESIGN AND SETTING: We conducted an experimental survey among corresponding authors of randomized controlled trials indexed in MEDLINE. We described two hypothetical studies and asked the respondents' opinion on the largest loss of effectiveness that is clinically negligible (or the smallest lost of effectiveness that is clinically important in the superiority scenario). We randomly manipulated four study attributes in each vignette, using a factorial design. RESULTS: A total of 364 researchers participated. The values for NIMs were significantly lower than the differences to be detected in a superiority trial. The NIM was smaller when the primary outcome was mortality compared with treatment failure, when baseline risk in the control arm was lower, and when the advantage of the new treatment was a lower cost compared with having fewer side effects. In contrast, the population age group under study and the difficulty to recruit patients showed no effect on the choice of the NIM. CONCLUSION: In our experimental study, the factors associated with lower NIMs were mortality as a primary outcome, low baseline risk, and a less costly new treatment.

Doctors' decisions when faced with contradictory patient advance directives and health care proxy opinion: a randomized vignette-based study.

CONTEXT: Sometimes a written advance directive contradicts the opinion of a health care proxy. How this affects doctors' decision making is unknown. OBJECTIVES: To quantify the influence of contradictory instructions on doctors' decisions. METHODS: All the generalists and internists in French-speaking Switzerland were mailed the questionnaire. Respondents (43.5%) evaluated three vignettes that described medical decisions for incapacitated patients. Each vignette was produced in four versions: one with an advance directive, one with a proxy opinion, one with both, and one with neither (control). In the first vignette, the directive and proxy agreed on the recommendation to forgo a medical intervention; in the second, the advance directive opposed, but the proxy favored the intervention; and in the third, the roles were reversed. Each doctor received one version of each vignette, attributed at random. The outcome variables were the doctor's decision to forgo the medical intervention and the rating of the decision as difficult. RESULTS: Written advance directives and proxy opinions significantly influenced doctors' decision making. When both were available and concordant, they reinforced each other (odds ratio [OR] of forgoing intervention 35.7, P < 0.001 compared with no instruction). When the directive and proxy disagreed, the resulting effect was to forgo the intervention (ORs 2.1 and 2.2 for the two discordant vignettes, both P < 0.001). Discordance between instructions was associated with increased odds of doctors rating the decision as difficult (both ORs 2.0, P ≤ 0.001). CONCLUSION: Contradictions between advance directives and proxy opinions result in a weak preference for abstention from treatment and increase the difficulty of the decision.

Effect of numbering of return envelopes on participation, explicit refusals, and bias: experiment and meta-analysis.

BACKGROUND: Tracing mail survey responses is useful for the management of reminders but may cause concerns about anonymity among prospective participants. We examined the impact of numbering return envelopes on the participation and the results of a survey on a sensitive topic among hospital staff. METHODS: In a survey about regrets associated with providing healthcare conducted among hospital-based doctors and nurses, two randomly drawn subsamples were provided numbered (N = 1100) and non-numbered (N = 500) envelopes for the return of completed questionnaires. Participation, explicit refusals, and item responses were compared. We also conducted a meta-analysis of the effect of questionnaire/envelope numbering on participation in health surveys. RESULTS: The participation rate was lower in the "numbered" group than in the "non-numbered" group (30.3% vs. 35.0%, p = 0.073), the proportion of explicit refusals was higher in the "numbered" group (23.1% vs 17.5%, p = 0.016), and the proportion of those who never returned the questionnaire was similar (46.6% vs 47.5%, p = 0.78). The means of responses differed significantly for 12 of 105 items (11.4%), which did not differ significantly from the expected frequency of type 1 errors, i.e., 5% (permutation test, p = 0.078). The meta-analysis of 7 experimental surveys (including this one) indicated that numbering is associated with a 2.4% decrease in the survey response rate (95% confidence interval 0.3% to 4.4%). CONCLUSIONS: Numbered return envelopes may reduce the response rate and increase explicit refusals to participate in a sensitive survey. Reduced participation was confirmed by a meta-analysis of randomized health surveys. There was no strong evidence of bias.

Impact of advance directives and a health care proxy on doctors' decisions: a randomized trial.

CONTEXT: Advance directives or proxy designations are widely recommended, but how they affect doctors' decision making is not well known. OBJECTIVES: The aim of this study was to quantify the influence of advance directives and proxy opinions on doctors' decisions. METHODS: We mailed to all the generalists and internists in French-speaking Switzerland (N = 1962) three vignettes describing difficult decisions involving incapacitated patients. In each case, the advance directive requested that further care be withheld. One vignette tested the impact of a written advance directive vs. a proxy. Another compared the impact of a handwritten directive vs. a formalized document. The third vignette compared the impact of a family member vs. a doctor as a proxy. Each vignette was prepared in three or four versions, including a control version in which no directive or proxy was present. Vignettes were randomly allocated to respondents. We used logistic regression to predict the decision to forgo a medical intervention. RESULTS: Compared with the control condition, the odds of forgoing a medical intervention were increased by the written advance directive (odds ratio [OR] 7.3; P < 0.001), the proxy (OR 7.9; P < 0.001), and the combination of the two (OR 35.7; P < 0.001). The handwritten directive had the same impact (OR 13.3) as the formalized directive (OR 13.8). The effect of proxy opinion was slightly stronger when provided by a doctor (OR 11.3) rather than by family (OR 7.8). CONCLUSION: Advance directives and proxy opinions are equally effective in influencing doctors' decisions, but having both has the strongest effect. The format of the advance directive and the identity of the proxy have little influence on decisions.