Individual- and regional-level determinants of human papillomavirus (HPV) vaccine refusal: the Ontario Grade 8 HPV vaccine cohort study.

BACKGROUND: Studies on the determinants of human papillomavirus (HPV) vaccine use have generally focused on individual-level characteristics, despite the potentially important influence of regional-level characteristics. Therefore, we undertook a population-based, retrospective cohort study to identify individual- and regional-level determinants of HPV vaccine refusal (non-receipt) in Ontario's (Canada) Grade 8 HPV Immunization Program. METHODS: Ontario's administrative health and immunization databases were used to identify girls eligible for free HPV vaccination in 2007-2011 and to ascertain individual-level characteristics of cohort members (socio-demographics, vaccination history, health care utilization, medical history). The social and material characteristics of the girl's region (health unit) were derived from the 2006 Canadian Census. Generalized estimating equations (binomial distribution, logit link) were used to estimate the population-average effects of individual- and regional-level characteristics on HPV vaccine refusal. RESULTS: Our cohort consisted of 144,047 girls, 49.3% of whom refused HPV vaccination. Factors associated with refusal included a previous diagnosis of Down's syndrome (OR = 1.37, 95% CI 1.16-1.63) or autism (OR = 1.60, 95% CI 1.34-1.90), few physician visits (OR = 1.45, 95% CI 1.35-1.55), and previous refusal of mandatory (OR = 2.23, 95% CI 2.07-2.40) and optional (OR = 3.96, 95% CI 3.87-4.05) vaccines. Refusal was highest among the lowest and highest income levels. Finally, a previous diagnosis of obesity and living in an area of high deprivation were associated with lower refusal (OR = 0.87, 95% CI 0.83-0.92 and OR = 0.82 95%, CI 0.79-0.86, respectively). CONCLUSIONS: Studies on HPV vaccine determinants should consider regional-level factors. Efforts to increase HPV vaccine acceptance should include vulnerable populations (such as girls of low income) and girls with limited contact with the healthcare system.

Using the incremental net benefit framework for quantitative benefit-risk analysis in regulatory decision-making--a case study of alosetron in irritable bowel syndrome.

OBJECTIVE: There is consensus that a more transparent, explicit, and rigorous approach to benefit-risk evaluation is required. The objective of this study is to evaluate the incremental net benefit (INB) framework for undertaking quantitative benefit-risk assessment by performing a quantitative benefit-risk analysis of alosetron for the treatment of irritable bowel syndrome from the patients' perspective. METHODS: A discrete event simulation model was developed to determine the INB of alosetron relative to placebo, calculated as "relative value-adjusted life-years (RVALYs)." RESULTS: In the base case analysis, alosetron resulted in a mean INB of 34.1 RVALYs per 1000 patients treated relative to placebo over 52 weeks of treatment. Incorporating parameter uncertainty into the model, probabilistic sensitivity analysis revealed a mean INB of 30.4 (95% confidence interval 15.9-45.4) RVALYs per 1000 patients treated relative to placebo over 52 weeks of treatment. Overall, there was >99% chance that both the incremental benefit and incremental risk associated with alosetron are greater than placebo. As hypothesized, the INB of alosetron was greatest in patients with the worst quality of life experienced at baseline. The mean INB associated with alosetron in patients with mild, moderate, and severe symptoms at baseline was 17.97 (-0.55 to 36.23), 29.98 (17.05-43.37), and 35.98 (23.49-48.77) RVALYs per 1000 patients treated, respectively. CONCLUSIONS: This study demonstrates the potential utility of applying the INB framework to real-life decision-making, and the ability to use simulation modeling incorporating outcomes data from different sources as a benefit-risk decision aid.

Pharmacists' preferences for providing patient-centered services: a discrete choice experiment to guide health policy.

BACKGROUND: In Canada, most pharmacists are not paid to provide patient-centered services. In other areas of the world these services have suffered from poor adoption by pharmacists. OBJECTIVE: To determine pharmacists' preferences for providing patient-centered services. METHODS: Senior pharmacy students and pharmacists in British Columbia and Alberta were recruited to complete a discrete choice experiment. In 18 different choice-sets, respondents were asked to choose 1 of 3 options that included 2 different hypothetical patient-centered services and a status quo option. For each hypothetical service, we described the following attributes: service type and setting, personal income and job satisfaction, professional fee, and educational requirements. Multinomial logit and latent class regression models determined respondents' relative preference weights for each attribute. RESULTS: Of 539 respondents who completed the questionnaire, 49% were dispensary pharmacists or managers, 12% were dispensary owners or regional managers, 21% were clinical pharmacists, and 16% were students. When choosing new services, respondents were very averse to having their personal income or job satisfaction decrease. They also preferred a higher professional fee for the service (to be paid to the pharmacy) and preferred a weeklong course or a preceptorship over no education before embarking on new services. Respondents also preferred medication or disease management services, were not interested in screening, and were averse to typical pharmacy services. Finally, respondents preferred the clinic setting over the dispensary. Preferences differed according to several factors including respondents' employment and time in practice. CONCLUSIONS: Pharmacists prefer to provide patient-centered services over typical pharmacy services. Most will need to be assured that their income and job satisfaction will be maintained or increased and that they will have access to suitable advanced education. Decision-makers should carefully consider these preferences to improve program success and sustainability.

A valuation of patients' willingness-to-pay for insulin delivery in diabetes.

OBJECTIVES: The aim of this study was to determine the insulin-delivery system and the attributes of insulin therapy that best meet patients' preferences, and to estimate patients' willingness-to-pay (WTP) for them. METHODS: This was a cross-sectional discrete choice experiment (DCE) study involving 378 Canadian patients with type 1 or type 2 diabetes. Patients were asked to choose between two hypothetical insulin treatment options made up of different combinations of the attribute levels. Regression coefficients derived using conditional logit models were used to calculate patients' WTP. Stratification of the sample was performed to evaluate WTP by predefined subgroups. RESULTS: A total of 274 patients successfully completed the survey. Overall, patients were willing to pay the most for better blood glucose control followed by weight gain. Surprisingly, route of insulin administration was the least important attribute overall. Segmented models indicated that insulin naïve diabetics were willing to pay significantly more for both oral and inhaled short-acting insulin compared with insulin users. Surprisingly, type 1 diabetics were willing to pay $C11.53 for subcutaneous short-acting insulin, while type 2 diabetics were willing to pay $C47.23 to avoid subcutaneous short-acting insulin (p < .05). These findings support the hypothesis of a psychological barrier to initiating insulin therapy, but once that this barrier has been overcome, they accommodate and accept injectable therapy as a treatment option. CONCLUSIONS: By understanding and addressing patients' preferences for insulin therapy, diabetes educators can use this information to find an optimal treatment approach for each individual patient, which may ultimately lead to improved control, through improved compliance, and better diabetes outcomes.

Health-related quality of life trajectories among adults with tuberculosis: differences between latent and active infection.

BACKGROUND: Tuberculosis (TB) remains a public health threat with significant annual impacts on morbidity and mortality. However, few studies have examined the impact of active and latent TB infection (LTBI) on health-related quality of life (HRQL). METHODS: Patients with recently diagnosed active TB or LTBI patients were administered the Short Form-36 (SF-36) and the Beck depression inventory (DI) at baseline, 3 months, and 6 months. Mixed-effect linear regression was used to compare the trajectory of HRQL over time in the two patient groups after adjusting for potential confounders. Ordinal logistic regression was used to determine the relationship between changes in HRQL of at least the minimal important difference. RESULTS: One hundred four active TB and 102 LTBI patients participated. At baseline, participants with active TB had significantly lower SF-36 mean domain and component scores (4 to 12 points lower, p < 0.03) and higher mean Beck DI scores (4 points higher, p < 0.0001) when compared to LBTI participants. In the responder analysis, those with active TB were associated with reporting improved scores at 6 months of at least the minimal important difference in vitality (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.3 to 5.6), role physical (OR, 3.1; 95% CI, 1.4 to 6.5), mental component score (OR, 3.2; 95% CI, 1.5 to 6.9), social functioning (OR, 11.1; 95% CI, 3.8 to 33), and role emotional (OR, 2.7; 95% CI, 1.2 to 6.0). CONCLUSIONS: Active TB patients had large improvements in most HRQL domains by 6 months. However, when compared to LTBI participants and US norms, HRQL was still low at completion of therapy.

Trends in nurse practitioners' prescribing to older adults in Ontario, 2000-2010: a retrospective cohort study.

BACKGROUND: Nurse prescribing is a practice that has evolved and will continue to evolve in response to emerging trends, particularly in primary care. The goal of this study was to describe the trends and patterns in medication prescription to adults 65 years of age or older in Ontario by nurse practitioners over a 10-year period. METHODS: We conducted a population-based descriptive retrospective cohort study. All nurse practitioners registered in the Corporate Provider Database between Jan. 1, 2000, and Dec. 31, 2010, were identified. We identified actively prescribing nurse practitioners through linkage of dispensed medications to people aged 65 years or older from the Ontario Drug Benefit database. For comparison, all prescription medications dispensed by family physicians to a similar group were identified. Geographic location was determined based on site of nurse practitioner practice. RESULTS: The number and proportion of actively prescribing nurse practitioners prescribing to older adults increased during the study period, from 44/340 (12.9%) to 888/1423 (62.4%). The number and proportion of medications dispensed for chronic conditions by nurse practitioners increased: in 2010, 9 of the 10 top medications dispensed were for chronic conditions. There was substantial variation in the proportion of nurse practitioners dispensing medication to older adults across provincial Local Health Integration Networks. INTERPRETATION: Prescribing by nurse practitioners to older adults, particularly of medications related to chronic conditions, increased between 2000 and 2010. The integration of nurse practitioners into primary care has not been consistent across the province and has not occurred in relation to population changes and perhaps population needs.

Risk of gastrointestinal events in patients with rheumatoid arthritis after withdrawal of rofecoxib.

OBJECTIVE: To examine the incidence of gastrointestinal (GI) events in patients with rheumatoid arthritis (RA) after the removal of rofecoxib from the market. METHODS: Residents of British Columbia with a diagnosis of RA who were chronic users of cyclooxygenase 2 (COX-2) inhibitors or nonselective nonsteroidal antiinflammatory drugs (nsNSAID) as of September 30, 2004, were included. We studied the risk of GI events using incidence rates and adjusted HR from Cox proportional hazards regression using time-dependent covariates. RESULTS: The cohort comprised 4266 patients with a mean age of 60 years and over 72% women, of which 2034 (48%) were classified as COX-2 inhibitor users and 2232 (52%) as chronic nsNSAID users as of September 30, 2004. The 2 groups were well balanced on baseline covariates except for comorbid conditions. In the year following rofecoxib withdrawal, 174 patients (5.5%) experienced 1 or more GI events, defined as a GI-related physician visit or hospitalization. There was no statistically significant increase in the risk of a GI event between those classified as a COX-2 inhibitor or nsNSAID user at the time of withdrawal (HR 1.03, 95% CI 0.69-1.54). Considering the drug exposure at the time of the event, there was no increased risk of GI events associated with the use of either COX-2 inhibitors or nsNSAID, or with the use of oral corticosteroids, low-dose aspirin, or clopidogrel, after adjustment for potential confounders. CONCLUSION: In this cohort, withdrawal of rofecoxib did not result in a significant increase in GI events among patients with RA.

Pharmacist-initiated intervention trial in osteoarthritis: a multidisciplinary intervention for knee osteoarthritis.

OBJECTIVE: Knee osteoarthritis (OA) is a commonly undiagnosed condition and care is often not provided. Pharmacists are uniquely placed for launching a multidisciplinary intervention for knee OA. METHODS: We performed a cluster randomized controlled trial with pharmacies providing either intervention care or usual care (14 and 18 pharmacies, respectively). The intervention included a validated knee OA screening questionnaire, education, pain medication management, physiotherapy-guided exercise, and communication with the primary care physician. Usual care consisted of an educational pamphlet. The primary outcome was the pass rate on the Arthritis Foundation's quality indicators for OA. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Lower Extremity Function Scale (LEFS), the Paper Adaptive Test-5D (PAT-5D), and the Health Utilities Index Mark 3 (HUI3). RESULTS: One hundred thirty-nine patients were assigned to the control (n = 66) and intervention (n = 73) groups. There were no differences between the groups in baseline measures. The overall quality indicator pass rate was significantly higher in the intervention arm compared to the control arm (difference of 45.2%; 95% confidence interval 34.5, 55.9). Significant improvements were observed for the intervention care group as compared to the usual care group in the WOMAC global, pain, and function scores at 3 and 6 months (all P < 0.01); the PAT-5D daily activity scores at 3 and 6 months (both P < 0.05); the PAT-5D pain scores at 6 months (P = 0.05); the HUI3 single-attribute pain scores at 3 and 6 months (all P < 0.05); and the LEFS scores at 6 months (P < 0.05). CONCLUSION: Pharmacists can launch a multidisciplinary intervention to identify knee OA cases, improve the utilization of treatments, and improve function, pain, and quality of life.

After patients are diagnosed with knee osteoarthritis, what do they do?

OBJECTIVE: To learn more about the health services and products that patients use after receiving a diagnosis of knee osteoarthritis (OA), as well as the trajectory of their health-related quality of life (HRQOL). METHODS: Using a simple screening survey, community pharmacists identified 194 participants with previously undiagnosed knee OA. Of these participants, 190 were confirmed to have OA on further investigation. At baseline and 1, 3, and 6 months after diagnosis, a survey was administered to assess health services, product use, and HRQOL, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Medical Outcomes Study Short Form 36 (SF-36) health survey, the Paper Adaptive Test (PAT-5D-QOL), and the Health Utilities Index Mark 3. RESULTS: With a mean age of 63 years, participants were mostly women, white, and overweight. By 6 months, more than 90% of the participants had visited their family physician to discuss their OA, and more than 50% of participants took either prescription or nonprescription analgesics. In addition, three-quarters of the participants started exercising, one-third initiated activity aids, and one-third had started natural medicine products. At 6 months compared with baseline, significant improvements were seen in the SF-36 physical component summary (P = 0.001) and bodily pain domain scores (P = 0.02), the PAT-5D-QOL overall, pain, and usual daily activities scores (P < 0.001 for all), and the WOMAC total, pain, and function scores (P < 0.001 for all). CONCLUSION: Within 6 months of receiving a diagnosis of knee OA, participants made several lifestyle interventions, often without the advice of a health professional, and saw improvements in their pain and function.

Inadequate statistical power to detect clinically significant differences in adverse event rates in randomized controlled trials.

OBJECTIVE: To determine the statistical power to detect potentially clinically significant differences in serious adverse events between drug therapies reported in a sample of randomized controlled trials (RCTs). STUDY DESIGN AND SETTING: Systematic review of RCTs with positive efficacy endpoint and at least a twofold difference in the proportion of patients with serious adverse events between treatment groups from six major journals. The power of each study to detect statistically significant differences in serious adverse events was calculated. RESULTS: Of the six included trials, all performed statistical analysis on adverse events without disclosure of the statistical power for detecting the reported differences between groups. The power of each study to detect the reported differences in adverse events was calculated and yielded values ranging from 0.07 to 0.37 among trials with non-statistically significant differences. CONCLUSION: Statistical testing for differences in the proportion of patients experiencing an adverse event is common in RCTs; non-statistically significant differences are associated with low statistical power. A high probability of type II error may lead to erroneous clinical inference resulting in harm. The statistical power for nonsignificant tests should be considered in the interpretation of results.

Socioeconomic differences in preferences and willingness-to-pay for insulin delivery systems in type 1 and type 2 diabetes.

BACKGROUND: An evaluation of patients' preferences is necessary to understand the demand for different insulin delivery systems. The aim of this study was to investigate the association between socioeconomic status (SES) and patients' preferences and willingness to pay (WTP) for various attributes of insulin administration for diabetes management. METHODS: We conducted a discrete choice experiment (DCE) to determine patients; preferences and their WTP for hypothetical insulin treatments. Both self-reported annual household income and education completed were used to explore differences in treatment preferences and WTP for different attributes of treatment across different levels of SES. RESULTS: The DCE questionnaire was successfully completed by 274 patients. Overall, glucose control was the most valued attribute by all socioeconomic groups, while route of insulin delivery was not as important. Patients with higher incomes were willing to pay significantly more for better glucose control and to avoid adverse events compared to lower income groups. In addition, they were willing to pay more for an oral short-acting insulin ($Can 71.65 [95% confidence interval, $40.68, $102.62]) compared to the low income group ($Can 9.85 [95% confidence interval, 14.86, 34.56; P < 0.01]). Conversely, there were no differences in preferences when the sample was stratified by level of education. CONCLUSIONS: This study revealed that preferences and WTP for insulin therapy are influenced by income but not by level of education. Specifically, the higher the income, the greater desire for an oral insulin delivery system, whereas an inhaled route becomes less important for patients.

Improving osteoarthritis detection in the community: pharmacist identification of new, diagnostically confirmed osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is the most common arthritis and a leading cause of disability. Many persons with knee OA are not diagnosed and not referred for treatment. Therefore, identification of patients with knee pain who have undiagnosed OA needs to be improved. Our objective was to determine if pharmacists, using a simple screening questionnaire, can identify individuals with previously undiagnosed knee OA. METHODS: Patients with knee pain and no previous diagnosis of knee OA were recruited by community pharmacists who used a simple questionnaire (<10 minutes to complete) to determine likelihood of knee OA. Patients who were likely to have knee OA were referred for a standardized knee examination and radiograph. RESULTS: Of the 411 patients screened by pharmacists, 274 were eligible. Of these, 44 declined, 35 were ineligible (18 had a previous OA diagnosis,16 had other inflammatory conditions, and 1 was excluded for other reasons), and 1 died. The remaining 194 were mostly female (62%) with a mean age of 62 years and were mostly white (86%). Body mass index (BMI) was classified as normal (18.5-24.9 kg/m(2)) in 29%, overweight (25.0-29.9 kg/m(2)) in 45%, and obese (>30.0 kg/m(2)) in 26%. Of those examined, 190 (98%) of 194 met the American College of Rheumatology clinical criteria for knee OA. The radiographic results revealed that most participants likely had mild OA. CONCLUSION: Pharmacists administering a simple screening questionnaire can identify >80% of patients with knee pain who have undiagnosed knee OA. Based on radiographs and BMI, much of this OA is early and may be amenable to intervention.