Andrea M. Burden

Interrupted time series analysis in drug utilization research is increasing: systematic review and recommendations

OBJECTIVES To describe the use and reporting of interrupted time series methods in drug utilization research. STUDY DESIGN AND SETTING We completed a systematic search of MEDLINE, Web of Science, and reference lists to identify English language articles through to December 2013 that used interrupted time series methods in drug utilization research. We tabulated the number of studies by publication year and summarized methodological detail. RESULTS We identified 220 eligible empirical applications since 1984. Only 17 (8%) were published before 2000, and 90 (41%) were published since 2010. Segmented regression was the most commonly applied interrupted time series method (67%). Most studies assessed drug policy changes (51%, n = 112); 22% (n = 48) examined the impact of new evidence, 18% (n = 39) examined safety advisories, and 16% (n = 35) examined quality improvement interventions. Autocorrelation was considered in 66% of studies, 31% reported adjusting for seasonality, and 15% accounted for nonstationarity. CONCLUSION Use of interrupted time series methods in drug utilization research has increased, particularly in recent years. Despite methodological recommendations, there is large variation in reporting of analytic methods. Developing methodological and reporting standards for interrupted time series analysis is important to improve its application in drug utilization research, and we provide recommendations for consideration.

Measuring and improving adherence to osteoporosis pharmacotherapy.

Purpose of reviewOsteoporosis is a major public health issue resulting in considerable fracture-related morbidity. Although effective treatment exists, adherence to osteoporosis pharmacotherapy is suboptimal and linked to reduced drug effectiveness. In this paper, we review methods of measuring and improving adherence to osteoporosis pharmacotherapy. Recent findingsMost patients will stop osteoporosis pharmacotherapy, yet the majority who discontinue will reinitiate treatment after an extended gap. The key to improving adherence to osteoporosis pharmacotherapy is to reduce the number and length of gaps in treatment. Multifaceted and individualized interventions may help to improve adherence. New strategies aimed at identifying patients likely to stop therapy may also facilitate the development of targeted interventions. SummaryAdherence to osteoporosis pharmacotherapy is suboptimal with short periods of persistence and lengthy gaps in therapy. Regular communication regarding the importance of continued therapy is critical. More research to help identify risk profiles of patients likely to become nonadherent, targeted multifaceted interventions to maximize adherence to therapy, and data to support when patients may safely consider a physician directed drug holiday is needed.

The impact of pharmacist interventions on osteoporosis management: a systematic review

SummaryWe completed a systematic review of the literature to examine the impact of pharmacist interventions in improving osteoporosis management. Results from randomized controlled trials suggest that pharmacist interventions may improve bone mineral density testing and calcium intake among patients at high risk for osteoporosis.IntroductionPharmacists play a key role in many healthcare systems by helping patients manage chronic diseases. We completed a systematic review of the literature to identify randomized controlled trials (RCTs) that have examined the impact of pharmacy interventions in narrowing two gaps in osteoporosis management: identifying at-risk individuals and improving adherence to therapy.MethodsWe searched the electronic databases of EMBASE, HealthStar, International Pharmaceutical Abstracts, MEDLINE, and PubMed from database development to April 2010, examined grey literature, and completed manual searches of reference lists to identify English-language research that examined osteoporosis management interventions within pharmacy practice. Results from RCTs were abstracted and assessed for bias.ResultsWe identified 25 studies that examined pharmacist interventions in osteoporosis management: 16 cohort, 5 cross-sectional, 1 historical/ecological control, and 3 RCTs. RCT interventions included osteoporosis educational and counseling programs, screening by pharmacists based on risk factor assessment or bone mineral density testing, and physician contact or recommendations for patients to follow-up with a general practitioner. Results from the three RCTs suggest that pharmacist interventions may improve bone mineral density testing (targeted screening) and calcium intake among patients at high risk for osteoporosis. However, two of the three RCTs had high risk of bias, and no study examined the impact of pharmacist intervention on osteoporosis treatment adherence.ConclusionsData support the potential role for pharmacists to help reduce gaps in osteoporosis management through improved identification of high-risk patients. More research is needed to examine pharmacist interventions on osteoporosis treatment adherence.

Case‐crossover study design in pharmacoepidemiology: systematic review and recommendations

The purpose of this study is to systematically identify and review articles that use the case‐crossover study design in the area of pharmacoepidemiology.

An Eight Component Decision-Making Model for Problem Gambling:A Systems Approach to Stimulate Integrative Research

Problem Gambling (PG) represents a serious problem for affected individuals, their families and society in general. Previous approaches to understanding PG have been confined to only a subset of the psychobiological factors influencing PG. We present a model that attempts to integrate potential causal factors across levels of organization, providing empirical evidence from the vast literature on PG and complimentary literatures in decision-making and addiction. The model posits that components are arranged systematically to bias decisions in favor of either immediately approaching or avoiding targets affording the opportunity for immediate reward. Dopamine, Testosterone and Endogenous Opioids favor immediate approach, while Serotonin and Cortisol favor inhibition. Glutamate is involved in associative learning between stimuli and promotes the approach response through its link to the DA reward system. GABA functions to monitor performance and curb impulsive decision-making. Finally, while very high levels of Norepinephrine can induce arousal to an extent that is detrimental to sound decision-making, the reactivity of the Norepinephrine system and its effects of Cortisol levels can shift the focus towards long-term consequences, thereby inhibiting impulsive decisions. Empirical evidence is provided showing the effects of each component on PG and decision-making across behavioural, neuropsychological, functional neuroimaging and genetic levels. Last, an effect size analysis of the growing pharmacotherapy literature is presented. It is hoped that this model will stimulate multi-level research to solidify our comprehension of biased decision-making in PG and suggest pharmacological and psychological approaches to treatment.

Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study

Objective To determine the association between use of sulphonylureas and risk of hypoglycaemia in relation to renal function and sulphonylurea metabolic group compared with use of metformin. Design Population based cohort study using routinely collected data from general practices in England. Setting Clinical Practice Research Datalink (CPRD) database, 2004-12. Participants 120 803 new users of a non-insulin antidiabetic agent with at least one prescription and aged 18 years or more. The first prescription defined start of follow-up. Patients were followed until the end of data collection, a record for hypoglycaemia, or a blood glucose level of less than 3.0 mmol/L. Main outcome measures Associations between sulphonylurea dose, renal impairment, type of sulphonylurea used, and risk of hypoglycaemia, were determined using Cox proportional hazard models. Adjustments were made for age, sex, lifestyle, comorbidity, and drug use. Results The risk of hypoglycaemia in current users of sulphonylureas only was significantly increased compared with current users of metformin only (adjusted hazard ratio 2.50, 95% confidence interval 2.23 to 2.82). The higher risk in current users of sulphonylureas only was further increased in patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 (4.96, 3.76 to 6.55). The risk of hypoglycaemia was also significantly higher in patients with a high sulphonylurea dose (3.12, 2.68 to 3.62) and in current users of glibenclamide (7.48, 4.89 to 11.44). Gliclazide, the sulphonylurea of first choice, showed a similar risk of hypoglycaemia compared with other sulphonylureas. Conclusions Sulphonylurea treatment in patients with a renal function of less than 30 mL/min/1.73 m2 should be considered with caution. Moreover, an increased risk of hypoglycaemic events was observed among all users of sulphonylureas. This contrasts with several guidelines that recommend gliclazide as first choice sulphonylurea, and therefore requires further investigation.

Use of dipeptidyl peptidase 4 inhibitors and fracture risk compared to use of other anti-hyperglycemic drugs

Dipeptidyl peptidase‐4 inhibitors (DPP4‐Is) are a new class of anti‐hyperglycemic drugs which might have a potential beneficial effect on bone metabolism. Data on the effect of DPP4‐I use and fracture risk is limited and conflicting. The aim of the present study was to investigate the association between use of DPP4‐Is and fracture risk.

Adherence to osteoporosis pharmacotherapy is underestimated using days supply values in electronic pharmacy claims data

Days supply (prescription duration) values are commonly used to estimate drug exposure and quantify adherence to therapy, yet accuracy is not routinely assessed, and potential inaccurate reporting has been previously identified. We examined the impact of cleaning days supply values on the measurement of adherence to oral bisphosphonates.

Initial uptake of the Ontario Pharmacy Smoking Cessation Program Descriptive analysis over 2 years

Background: Smoking is a significant public health concern. The Ontario Pharmacy Smoking Cessation Program was launched in September 2011 to leverage community pharmacists and expand access to smoking cessation services for public drug plan beneficiaries. Methods: We examined health care utilization data in Ontario to describe public drug plan beneficiaries receiving, and pharmacies providing, smoking cessation services between September 2011 and September 2013. Patient characteristics were summarized, stratified by drug plan group: seniors (age ≥65 years) or social assistance. Trends over time were examined by plotting the number of services, unique patients and unique pharmacies by month. We then examined use of follow-up services and prescription smoking cessation medications. Results: We identified 7767 residents receiving pharmacy smoking cessation services: 28% seniors (mean age = 69.9, SD = 4.8; 53% male) and 72% social assistance (mean age = 44.4 years, SD = 11.8; 48% male). Cumulative patient enrollment increased over time with an average of 311 (SD = 61) new patients per month, and one-third (n = 1253) of pharmacies participated by the end of September 2013. Regions with the highest number of patients were Erie St. Clair (n = 1328) and Hamilton Niagara Haldimand Brant (n = 1312). Sixteen percent of all patients received another pharmacy service (e.g., MedsCheck) on the same day as smoking cessation program enrollment. Among patients with follow-up data, 56% received follow-up smoking cessation services (60% seniors, 55% social assistance) and 74% received a prescription smoking cessation medication. One-year quit status was reported for 12%, with a 29% success rate. Conclusions: Program enrollment has increased steadily since its launch, yet only a third of pharmacies participated and 56% of patients received follow-up services.

Patterns of use for brand-name versus generic oral bisphosphonate drugs in Ontario over a 13-year period: a descriptive study

BACKGROUND Bisphosphonates are the first-line therapy for the treatment of osteoporosis. In the province of Ontario, the Ontario Drug Benefit Program funds medications for patients aged 65 years and older. The Ontario Drug Benefit Program has a generic substitution policy that requires lower-cost generic drugs to be dispensed when they are available. However, there is controversy surrounding the efficacy and tolerability of generic bisphosphonates. The objective of this study was to describe patterns in the use of brand-name versus generic formulations when dispensing oral bisphosphonate over a 13-year period. METHODS We identified all osteoporotic preparations for alendronate and risedronate that were dispensed through the Ontario Drug Benefit Program from 2001 to 2014. We stratified our sample into community-dwelling residents and residents in long-term care facilities. The number of prescriptions dispensed per month were plotted to illustrate trends over time. RESULTS We found a rapid switch from brand-name to generic bisphosphonate equivalents immediately after the generic became available on the Ontario Drug Benefit formulary, with generics accounting for > 88% of dispensed drug within 2 months. We also observed a reduction in the number of generic drugs dispensed each time a new brand-name alternative (e.g., monthly risedronate, weekly alendronate plus vitamin D) was introduced to the formulary. The dispensing trends were similar in the community and long-term care settings. INTERPRETATION The Ontario Drug Benefit Program generic substitution policy resulted in rapid uptake of generic oral bisphosphonates among seniors in Ontario. However, there was a switch away from generic medications to new brand-name alternatives whenever they were introduced to the formulary. Therefore, some patients continued to use brand-name bisphosphonate despite the availability of generic options.