Richard Birtwhistle

Pragmatic controlled clinical trials in primary care: the struggle between external and internal validity

BackgroundControlled clinical trials of health care interventions are either explanatory or pragmatic. Explanatory trials test whether an intervention is efficacious; that is, whether it can have a beneficial effect in an ideal situation. Pragmatic trials measure effectiveness; they measure the degree of beneficial effect in real clinical practice. In pragmatic trials, a balance between external validity (generalizability of the results) and internal validity (reliability or accuracy of the results) needs to be achieved. The explanatory trial seeks to maximize the internal validity by assuring rigorous control of all variables other than the intervention. The pragmatic trial seeks to maximize external validity to ensure that the results can be generalized. However the danger of pragmatic trials is that internal validity may be overly compromised in the effort to ensure generalizability. We are conducting two pragmatic randomized controlled trials on interventions in the management of hypertension in primary care. We describe the design of the trials and the steps taken to deal with the competing demands of external and internal validity.DiscussionExternal validity is maximized by having few exclusion criteria and by allowing flexibility in the interpretation of the intervention and in management decisions. Internal validity is maximized by decreasing contamination bias through cluster randomization, and decreasing observer and assessment bias, in these non-blinded trials, through baseline data collection prior to randomization, automating the outcomes assessment with 24 hour ambulatory blood pressure monitors, and blinding the data analysis.SummaryClinical trials conducted in community practices present investigators with difficult methodological choices related to maintaining a balance between internal validity (reliability of the results) and external validity (generalizability). The attempt to achieve methodological purity can result in clinically meaningless results, while attempting to achieve full generalizability can result in invalid and unreliable results. Achieving a creative tension between the two is crucial.

Anti-diabetic and hypoglycaemic effects of Momordica charantia (bitter melon): a mini review.

It has been estimated that up to one-third of patients with diabetes mellitus use some form of complementary and alternative medicine. Momordica charantia (bitter melon) is a popular fruit used for the treatment of diabetes and related conditions amongst the indigenous populations of Asia, South America, India and East Africa. Abundant pre-clinical studies have documented the anti-diabetic and hypoglycaemic effects of M. charantia through various postulated mechanisms. However, clinical trial data with human subjects are limited and flawed by poor study design and low statistical power. The present article reviews the clinical data regarding the anti-diabetic potentials of M. charantia and calls for better-designed clinical trials to further elucidate its possible therapeutic effects.

Recommendations on screening for cervical cancer

cervical cancer were diagnosed in Canada, with about 350 deaths. The number of cases of diagnosed cervical cancer in creases among women aged 25 years and older, peaking during the fifth decade of life (Figure 1). The incidence of and mortality due to cervical cancer in Canada have decreased substantially in the past 50 years, and long-term survival rates after treatment are high. Lifetime incidence was 1.5% in 1972, and is now 0.7%; risk of death from cervical cancer is now 0.2%. Most advanced cervical cancer (and associated mortality) occurs among women who have never undergone screening or who have had a long interval between Papanicolaou (Pap) tests. Screening for cervival cancer using the Pap test detects precursor lesions, thereby allowing earlier and potentially less invasive treatment than is re quired for disease that causes symptoms. The benefits of such screening on the incidence of invasive disease and death due to cervical cancer have been consistently shown in cohort and case–control studies. It is likely that much of the change seen in the incidence of cervical cancer in Canada is due to screening, but early and frequent (often annual) cervical screening is unnecessary: other countries have achieved similar outcomes with less frequent testing and starting screening at older ages. The similar levels of success with different approaches highlights uncertainties regarding the best ages at which to start and stop screening, screening intervals and screening methods. Furthermore, the benefits of screening must be balanced against its potential harms, such as additional follow-up tests for abnormal results and unnecessary treatment (e.g., owing to false -positives and overdiagnosis). The likelihood of abnormal Pap test results is highest for young women, and decreases with increasing age. Because the prevalence of highgrade abnormalities declines steadily with age, al though the incidence of cancer is higher, the proportion of abnormal results that represent serious abnormalities is greater among older women. Women whose initial Pap test result is abnormal may be asked to undergo a repeat test or have a colposcopy. The colposcopist may then biopsy the cervix. If the biopsy shows cervical intra epithelial neoplasia, the colposcopist may then treat the cervix by excising the transformation zone using various methods. These procedures cause short-term pain, bleeding and discharge, and may cause early loss of future pregnancies or premature labour. It is likely that many of these procedures can be considered overtreatment, because fewer than one-third of even high-grade abnormalities progress to cancer. This guideline provides updated recommendations for screening for cervical cancer in Canada based on new information about the epidemiology and diagnosis of cervical cancer and a new systematic search of the literature. This guideline updates the recommendations of the Canadian Task Force on Preventive Health Care that were last revised in 1994. Recommendations are presented for the use of Pap tests for women with no symptoms of cervical cancer who are or who have been sexually active, regardless of sexual orientation. Separate recommendations are provided for screening in women in the following age categories: younger than 20 years, 20–24 years, 25–29 years, 30– 69 years and 70 years or older. Re com mend ations Recommendations on screening for cervical cancer

Building a Pan-Canadian Primary Care Sentinel Surveillance Network: Initial Development and Moving Forward

The development of a pan-Canadian network of primary care research networks for studying issues in primary care has been the vision of Canadian primary care researchers for many years. With the opportunity for funding from the Public Health Agency of Canada and the support of the College of Family Physicians of Canada, we have planned and developed a project to assess the feasibility of a network of networks of family medicine practices that exclusively use electronic medical records. The Canadian Primary Care Sentinel Surveillance Network will collect longitudinal data from practices across Canada to assess the primary care epidemiology and management of 5 chronic diseases: hypertension, diabetes, depression, chronic obstructive lung disease, and osteoarthritis. This article reports on the 7-month first phase of the feasibility project of 7 regional networks in Canada to develop a business plan, including governance, mission, and vision; develop memorandum of agreements with the regional networks and their respective universities; develop and obtain approval of research ethics board applications; develop methods for data extraction, a Canadian Primary Care Sentinel Surveillance Network database, and initial assessment of the types of data that can be extracted; and recruitment of 10 practices at each network that use electronic medical records. The project will continue in phase 2 of the feasibility testing until April 2010.

Validating the 8 CPCSSN Case Definitions for Chronic Disease Surveillance in a Primary Care Database of Electronic Health Records

PURPOSE The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) is Canada’s first national chronic disease surveillance system based on electronic health record (EHR) data. The purpose of this study was to develop and validate case definitions and case-finding algorithms used to identify 8 common chronic conditions in primary care: chronic obstructive pulmonary disease (COPD), dementia, depression, diabetes, hypertension, osteoarthritis, parkinsonism, and epilepsy. METHODS Using a cross-sectional data validation study design, regional and local CPCSSN networks from British Columbia, Alberta (2), Ontario, Nova Scotia, and Newfoundland participated in validating EHR case-finding algorithms. A random sample of EHR charts were reviewed, oversampling for patients older than 60 years and for those with epilepsy or parkinsonism. Charts were reviewed by trained research assistants and residents who were blinded to the algorithmic diagnosis. Sensitivity, specificity, and positive and negative predictive values (PPVs, NPVs) were calculated. RESULTS We obtained data from 1,920 charts from 4 different EHR systems (Wolf, Med Access, Nightingale, and PS Suite). For the total sample, sensitivity ranged from 78% (osteoarthritis) to more than 95% (diabetes, epilepsy, and parkinsonism); specificity was greater than 94% for all diseases; PPV ranged from 72% (dementia) to 93% (hypertension); NPV ranged from 86% (hypertension) to greater than 99% (diabetes, dementia, epilepsy, and parkinsonism). CONCLUSIONS The CPCSSN diagnostic algorithms showed excellent sensitivity and specificity for hypertension, diabetes, epilepsy, and parkinsonism and acceptable values for the other conditions. CPCSSN data are appropriate for use in public health surveillance, primary care, and health services research, as well as to inform policy for these diseases.

Recommendations on screening for colorectal cancer in primary care

340 CMAJ, March 15, 2016, 188(5) ©2016 8872147 Canada Inc. or its licensors Colorectal cancer is the second most common cause of cancer-related death in men and the third most common in women;1 the lifetime probabilities of dying from colorectal cancer among men and women are 3.5% and 3.1%, respectively.2 Although the burden of colorectal cancer varies across Canada,3 it is estimated that 25 000 Canadians received a diagnosis of colorectal cancer in 2015 (incidence 49 per 100 000 population) and that 9300 will die from the disease (mortality 17 per 100 000).1 The incidence and mortality of colorectal cancer are low until middle age and rise rapidly thereafter (Figure 1).1,4 Most colorectal cancers appear to arise from colonic polyps that develop slowly and sometimes transform to cancers.5 This is the ration ale for screening programs that aim to reduce deaths due to colorectal cancer by detecting and removing polyps and/or early-stage colorectal cancers. Implementation of organized screening programs in some Canadian provinces has been associated with an increase in the number of individuals screened,6 and other provinces are in the process of implementing such programs (Appendix 1, available at www.cmaj.ca/lookup/ suppl/doi:10.1503/cmaj.151125/-/DC1). Currently, all Canadian programs recommend screening with guaiac fecal occult blood testing (gFOBT) or fecal immunochemical testing (FIT). This guideline presents recommendations for screening for colorectal cancer in asymptomatic adults aged 50 years and older who are not at high risk for colorectal cancer, and it updates previous Canadian Task Force on Preventive Health Care recommendations from 2001.7 The 2001 guideline recommended annual or biennial FOBT (grade A recommendation) and flexible sigmoidoscopy every five years (grade B recommendation) in asymptomatic people older than 50 years. The guideline did not recommend whether these screening modalities should be used alone or in combination (grade C),7,8 or whether to include or exclude colonoscopy as an initial screening test for colorectal cancer. Given the major changes in technology and practice since 2001, the guideline has been updated based on the most recent data available to provide guidance for primary care practitioners on different screening tests, screening intervals and recommended ages to start and stop screening.

Manual and automated office measurements in relation to awake ambulatory blood pressure monitoring

BACKGROUND Automated blood pressure (BP) devices are commonly used in doctors offices. How BP measured on these devices relates to ambulatory BP monitoring is not clear. OBJECTIVE To assess how well office-based manual and automated BP predicts ambulatory BP. METHODS Using data on 654 patients, we assessed how well sphygmomanometer measurements and measurements taken with an automated device (BpTRU) predicted results on ambulatory BP monitoring. We assess positive and negative predictive values and overall accuracy. We look at different cut-points for systolic (130, 135 and 140 mmHg) and diastolic (80, 85 and 90 mmHg) BP. RESULTS A single automated office BP (AOBP) assessment provides superior predictive values and overall accuracy compared to three manual office BP assessments. For systolic BP, the predictive values are ≤69% for any of the cut-points while the positive predictive values for the single automated measurement is between 80.0% and 86.9% and the overall accuracy gets as high as 74% for the 130 mmHg cut-point. For diastolic BP, the automated readings are also more predictive but in this case, it is the negative predictive values that are better, as well as the overall accuracy. CONCLUSIONS Based on the results, we suggest that 135/85 mmHg continue to be used as the cut-point defining high BP with the BpTRU device. However, future research might suggests that values in a grey zone between 130-139 mmHg systolic and 80-89 mmHg diastolic be confirmed using ambulatory BP monitoring. As well, three AOBP assessments might produce much greater accuracy than the single AOBP assessment used in the study.

Assessing methods for measurement of clinical outcomes and quality of care in primary care practices.

PurposeTo evaluate the appropriateness of potential data sources for the population of performance indicators for primary care (PC) practices.MethodsThis project was a cross sectional study of 7 multidisciplinary primary care teams in Ontario, Canada. Practices were recruited and 5-7 physicians per practice agreed to participate in the study. Patients of participating physicians (20-30) were recruited sequentially as they presented to attend a visit. Data collection included patient, provider and practice surveys, chart abstraction and linkage to administrative data sets. Matched pairs analysis was used to examine the differences in the observed results for each indicator obtained using multiple data sources.ResultsSeven teams, 41 physicians, 94 associated staff and 998 patients were recruited. The survey response rate was 81% for patients, 93% for physicians and 83% for associated staff. Chart audits were successfully completed on all but 1 patient and linkage to administrative data was successful for all subjects. There were significant differences noted between the data collection methods for many measures. No single method of data collection was best for all outcomes. For most measures of technical quality of care chart audit was the most accurate method of data collection. Patient surveys were more accurate for immunizations, chronic disease advice/information dispensed, some general health promotion items and possibly for medication use. Administrative data appears useful for indicators including chronic disease diagnosis and osteoporosis/ breast screening.ConclusionsMultiple data collection methods are required for a comprehensive assessment of performance in primary care practices. The choice of which methods are best for any one particular study or quality improvement initiative requires careful consideration of the biases that each method might introduce into the results. In this study, both patients and providers were willing to participate in and consent to, the collection and linkage of information from multiple sources that would be required for such assessments.

A primary care pragmatic cluster randomized trial of the use of home blood pressure monitoring on blood pressure levels in hypertensive patients with above target blood pressure

BACKGROUND The measurement of blood pressure (BP) at home by patients with hypertension is increasingly used to assess and monitor BP. Evidence for its effectiveness in improving BP control is mixed. METHODS To determine if home BP monitoring improves BP a pragmatic cluster randomized contolled trial was carried out in family practices in southeastern Ontario, Canada. Family practice patients with uncontrolled hypertension were recruited to the trail. Patients were divided into two groups: one with at least weekly measurements of BP at home, recording those measurements and showing those to the family physician during office visits for hypertension and the control group were given usual care. The primary outcome was mean awake BP on ambulatory monitoring at 6- and 12-month follow-up and the secondary outcomes were mean BP on full 24-hour ambulatory blood pressure monitoring (ABPM), mean sleep BP on ABPM and BP on the BpTRU device, all at 6- and 12-month follow-up. RESULTS Home BP monitoring did not improve BP compared to usual care at 12-month follow-up: mean awake systolic BP on ABPM [141.1 versus 142.8 mmHg, mean difference 1.7 mmHg; 95% confidence interval (CI) -0.6 to 4.0, P = 0.314] and mean awake diastolic BP on ABPM (78.7 versus 79.4 mmHg, mean difference 0.7 mmHg; 95% CI -7.7 to 9.1, P = 0.398). Similar negative results were obtained for men and women separately. However, outcomes using the full 24-hour ABPM and the BpTRU device showed a significantly lower diastolic BP at 12 months. When analysis was done by sex, this effect was shown to be only in men. CONCLUSION Home BP monitoring may improve BP control in men with hypertension.

Development Of The Approaches To Work And Workplace Climate Questionnaires For Physicians

Two questionnaires were developed to investigate the workplace learning of physicians. The Approaches to Work Questionnaire for Physicians and the Workplace Climate Questionnaire for Physicians were adapted from general measures developed by Kirby, Knapper, Evans, Carty, and Gadula. These questionnaires were administered to a random sample of Ontario physicians. Consistent with the results of Kirby et al., three dimensions of approaches to work were observed: Deep, Surface-Rational, and Surface-Disorganized. Three dimensions of workplace climate were also found, Supportive-Receptive, Choice-Independence, and Workload. Results indicate that physicians adopt primarily a Deep approach to work, but that there is a smaller tendency toward Surface-Disorganized learning, one that is strongly correlated with perceptions of heavy workload. The Deep approach was associated with work environments perceived to be Supportive-Receptive and offer Choice-Independence. The use of these questionnaires in research and practice is discussed.