Multivariable risk prediction can greatly enhance the statistical power of clinical trial subgroup analysis

BACKGROUND: When subgroup analyses of a positive clinical trial are unrevealing, such findings are commonly used to argue that the treatment's benefits apply to the entire study population; however, such analyses are often limited by poor statistical power. Multivariable risk-stratified analysis has been proposed as an important advance in investigating heterogeneity in treatment benefits, yet no one has conducted a systematic statistical examination of circumstances influencing the relative merits of this approach vs. conventional subgroup analysis. METHODS: Using simulated clinical trials in which the probability of outcomes in individual patients was stochastically determined by the presence of risk factors and the effects of treatment, we examined the relative merits of a conventional vs. a "risk-stratified" subgroup analysis under a variety of circumstances in which there is a small amount of uniformly distributed treatment-related harm. The statistical power to detect treatment-effect heterogeneity was calculated for risk-stratified and conventional subgroup analysis while varying: 1) the number, prevalence and odds ratios of individual risk factors for risk in the absence of treatment, 2) the predictiveness of the multivariable risk model (including the accuracy of its weights), 3) the degree of treatment-related harm, and 5) the average untreated risk of the study population. RESULTS: Conventional subgroup analysis (in which single patient attributes are evaluated "one-at-a-time") had at best moderate statistical power (30% to 45%) to detect variation in a treatment's net relative risk reduction resulting from treatment-related harm, even under optimal circumstances (overall statistical power of the study was good and treatment-effect heterogeneity was evaluated across a major risk factor [OR = 3]). In some instances a multi-variable risk-stratified approach also had low to moderate statistical power (especially when the multivariable risk prediction tool had low discrimination). However, a multivariable risk-stratified approach can have excellent statistical power to detect heterogeneity in net treatment benefit under a wide variety of circumstances, instances under which conventional subgroup analysis has poor statistical power. CONCLUSION: These results suggest that under many likely scenarios, a multivariable risk-stratified approach will have substantially greater statistical power than conventional subgroup analysis for detecting heterogeneity in treatment benefits and safety related to previously unidentified treatment-related harm. Subgroup analyses must always be well-justified and interpreted with care, and conventional subgroup analyses can be useful under some circumstances; however, clinical trial reporting should include a multivariable risk-stratified analysis when an adequate externally-developed risk prediction tool is available

Documentation of preventive screening interventions by general practitioners: a retrospective chart audit

<p>Abstract</p> <p>Background</p> <p>Screening and early diagnosis has been shown to reduce the morbidity and mortality associated with certain conditions such as cervical cancer. The role of general practitioners in promoting primary prevention of diseases is particularly important given that they have frequent contact with a large proportion of the population. This study assessed the extent to which general practitioners documented recommended preventive screening interventions among eligible patients.</p> <p>Methods</p> <p>We used a retrospective chart audit to assess patient visits to primary care clinics in Calgary, Canada from 2002-2004. We included fee for service physicians who practiced ≥ 2 days per week at their current location and excluded those whose primary practice was at walk-in clinics, community health centers, hospitals or emergency rooms. We included charts of patients who during the study period were age 35 years or older and had at least 2 visits to a clinic. We randomly selected and reviewed charts (N = 600) from 12 primary care clinics and abstracted information on 6 conditions recommended for preventive screening. Opportunities for preventive screening were determined based on recommendations of the Canadian Task Force on Preventive Health Care, the American College of Physicians, and the Canadian Cancer Society. Our main outcome measures included cancer screening (mammography and pap smears), immunization (influenza and pneumococcal), and risk factor assessment (cholesterol measurement and smoking cessation consultation).</p> <p>Results</p> <p>Patient visits to GP clinics present opportunities for preventive screening. However, we found that documentation of interventions was low, ranging from 40.3% (cholesterol measurement) to 0.9% (pneumococcal vaccination) within 1 year, and from 67.4% to 1.8% within the prior 3 years.</p> <p>Conclusions</p> <p>Documentation of preventive screening interventions by general practitioners was relatively low compared to the number of patients eligible for preventive screening. Some physicians opt to screen for PSA and DRE which is not recommended by the Canadian Task Force on Preventive HealthCare.</p

Nurses' perceived barriers to the implementation of a Fall Prevention Clinical Practice Guideline in Singapore hospitals

BackgroundTheories of behavior change indicate that an analysis of barriers to change is helpful when trying to influence professional practice. The aim of this study was to assess the perceived barriers to practice change by eliciting nurses\u27 opinions with regard to barriers to, and facilitators of, implementation of a Fall Prevention clinical practice guideline in five acute care hospitals in Singapore.MethodsNurses were surveyed to identify their perceptions regarding barriers to implementation of clinical practice guidelines in their practice setting. The validated questionnaire, \u27Barriers and facilitators assessment instrument\u27, was administered to nurses (n = 1830) working in the medical, surgical, geriatric units, at five acute care hospitals in Singapore.ResultsAn 80.2% response rate was achieved. The greatest barriers to implementation of clinical practice guidelines reported included: knowledge and motivation, availability of support staff, access to facilities, health status of patients, and, education of staff and patients.ConclusionNumerous barriers to the use of the Fall Prevention Clinical Practice Guideline have been identified. This study has laid the foundation for further research into implementation of clinical practice guidelines in Singapore by identifying barriers to change in acute care settings.<br /

Evidence-Based Medicine and the Practicing Clinician

OBJECTIVE: To assess the attitudes of practicing general internists toward evidence-based medicine (EBM—defined as the process of systematically finding, appraising, and using contemporaneous research findings as the basis for clinical decisions) and their perceived barriers to its use. DESIGN: Cross-sectional, self-administered mail questionnaire conducted between June and October 1997. SETTING: Canada. PARTICIPANTS: Questionnaires were sent to all 521 physician members of the Canadian Society of Internal Medicine with Canadian mailing addresses; 296 (60%) of 495 eligible physicians responded. Exclusion of two incomplete surveys resulted in a final sample size of 294. MAIN RESULTS: Mean age of respondents was 46 years, 80% were male, and 52% worked in large urban medical centers. Participants reported using EBM in their clinical practice always (33, 11%), often (173, 59%), sometimes (80, 27%), or rarely/never (8, 3%). There were no significant differences in demographics, training, or practice types or locales on univariate or multivariate analyses between those who reported using EBM often or always and those who did not. Both groups reported high usage of traditional (non-EBM) information sources: clinical experience (93%), review articles (73%), the opinion of colleagues (61%), and textbooks (45%). Only a minority used EBM-related information sources such as primary research studies (45%), clinical practice guidelines (27%), or Cochrane Collaboration Reviews (5%) on a regular basis. Barriers to the use of EBM cited by respondents included lack of relevant evidence (26%), newness of the concept (25%), impracticality for use in day-to-day practice (14%), and negative impact on traditional medical skills and “the art of medicine” (11%). Less than half of respondents were confident in basic skills of EBM such as conducting a literature search (46%) or evaluating the methodology of published studies (34%). However, respondents demonstrated a high level of interest in further education about these tasks. CONCLUSIONS: The likelihood that physicians will incorporate EBM into their practice cannot be predicted by any demographic or practice-related factors. Even those physicians who are most enthusiastic about EBM rely more on traditional information sources than EBM-related sources. The most important barriers to increased use of EBM by practicing clinicians appear to be lack of knowledge and familiarity with the basic skills, rather than skepticism about the concept