Improving medication prescribing-related outcomes for vulnerable elderly in transitions on high-risk medications (IMPROVE-IT HRM): a pilot randomized trial protocol.

BACKGROUND: Seniors with recurrent hospitalizations who are taking multiple medications including high-risk medications are at particular risk for serious adverse medication events. We will assess whether an expert Clinical Pharmacology and Toxicology (CPT) medication management intervention during hospitalization with follow-up post-discharge and communication with circle of care is feasible and can decrease drug therapy problems amongst this group. METHODS: The design is a pragmatic pilot randomized trial with 1:1 patient-level concealed randomization with blinded outcome assessment and data analysis. Participants will be adults 65 years and older admitted to internal medicine services for more than 2 days, who have had at least one other hospitalization in the prior year, taking five or more chronic medications including at least one high-risk medication. The CPT intervention identifies medication targets; completes consult, including priorities for improving prescribing negotiated with the patient; starts the care plan; ensures a detailed discharge medication reconciliation and circle-of-care communication; and sees the patient at least twice after hospital discharge via virtual visits to consolidate the care plan in the community. Control group receives usual care. Primary outcomes are feasibility - recruitment, retention, costs, and clinical - number of drug therapy problems improved, with secondary outcomes examining coordination of transitions in care, quality of life, and healthcare utilization and costs. Follow-up is to 3-month posthospital discharge. DISCUSSION: If results support feasibility of ramp-up and promising clinical outcomes, a follow-up definitive trial will be organized using a developing national platform and medication appropriateness network. Since the intervention allows a very scarce medical specialty expertise to be offered via virtual care, there is potential to improve the safety, outcomes, and cost of care widely. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04077281.

Onwards and Upwards: A Systematic Survey of Economic Evaluation Methods in Oncology.

INTRODUCTION: The type of methods used in economic evaluations of health technology can lead to results that may influence decisions. Despite the potential impact on decision making, there is very little documentation of methods used in economic evaluation in oncology pertaining to key assumptions and extrapolation methods of survival benefits, especially in terms of survival analysis techniques and methods for extrapolation. OBJECTIVES: The primary objectives of this study were to identify, examine, and describe the methods used in economic evaluations in oncology over a 10-year period, while secondary objectives included examining the use of identified methods across different geographic regions. METHODS: A systematic search of the published oncology literature was conducted to identify economic evaluations of advanced or metastatic cancers published between 2010 and 2019 using the PUBMED, Ovid MEDLINE, and EMBASE databases. A random sample was taken, and information on type of study, data source, modeling techniques, and survival analysis methods were abstracted and descriptively summarized. RESULTS: A total of 8481 abstracts were identified and 76 economic evaluations were abstracted and assessed. Most identified studies were from North America (38%), East Asia (21%), continental Europe (18%), or the UK (16%), and most commonly focused on lung cancer (18%), colorectal cancer (16%), or breast cancer (13%). A large majority of studies were based on data from randomized controlled trials (82%), utilized a cost-utility approach (82%), and took a public healthcare system perspective (83%). Common model structures included Markov (49%) and partitioned survival (17%). Fitted parametric curves were the most commonly used extrapolation method (89%) for overall survival and most often utilized the Weibull distribution (64%). Secondary assessments showed modest regional variation in the use of identified methods, including the use of fitted parametric curves, testing of the proportional hazards assumption, and validation of results. CONCLUSION: A majority of papers in the study sample reported basic characteristics of study type, data source used, modeling techniques, and utilization of survival analysis methods. However, greater detail in reporting extrapolation methods, statistical analyses, and validation of results could be potential improvements, especially across regions, in order to support greater consistency in decision making. Future research could document the diffusion of novel modeling techniques into economic evaluation.

A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

BACKGROUND: In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. METHODS: Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. FINDINGS: Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. INTERPRETATION: Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

Emergency Department and Walk-in Clinic Use in Models of Primary Care Practice with Different After-Hours Accessibility in Ontario.

INTRODUCTION: New models of primary healthcare delivery recently implemented in Ontario are designed to improve after-hours accessibility. This study examined whether the six-month prevalence of emergency department and walk-in clinic use differed among patients of eight Family Health Network (FHN), 16 Family Health Group (FHG) and 12 fee-for-service (FFS) physicians in one city. METHODS: Patients over one year of age who had visited their family doctor in the previous 12 months (n=9,373) were randomly selected from computerized records. A mailed survey asked about urgent health problems in the previous six months and use of health services for those problems. A generalized estimating equation approach was used to compare the proportions of patients using the emergency department and walk-in clinic in the FHN versus other practice types, adjusting for clustering of patients within practices. Multiple imputation was used to impute data for non-respondents and missing items on the surveys. RESULTS: The response rate was 62.3% (5,884/9,373). Six-month prevalence of emergency department use was 11.4% (199/1,753) among the FHN practices, 15.7% (347/2,236) among the FHG practices (odds ratio [OR] = 1.47; 95% confidence interval [CI] = 1.21-1.80) and 14.3% (252/1,779) among the FFS practices (OR=1.33; 95% CI=1.12-1.59). Six-month prevalence of walk-in clinic use was 1.7% (30/1,723) among the FHN practices versus 1.9% (41/2,236) in the FHG practices (OR=1.07; 95% CI=0.68-1.68) and 3.4% (59/1,779) among the FFS practices (OR=2.08; 95% CI=1.41-3.08). The statistical significance of results was unchanged using multiple imputation. CONCLUSIONS: Patients' use of the emergency department and walk-in clinics differs across primary care practice models with different after-hours accessibility arrangements and incentives.

Temporal trends in antihypertensive drug prescriptions in Canada before and after introduction of the Canadian Hypertension Education Program.

OBJECTIVE: Poor control of hypertension is a world-wide health issue. In 1999, the Canadian Hypertension Education Program (CHEP) was launched to annually develop and implement evidence-based hypertension guidelines in an effort to improve hypertension control rates. This study was designed to examine temporal trends in antihypertensive drug prescribing and to explore whether drug prescriptions changed after initiation of the new CHEP guideline process. DESIGN AND METHODS: We used longitudinal Canadian dispensing data (from the IMS CompuScript database; IMS Health, Pointe-Claire, Quebec) to examine antihypertensive prescriptions in the 3 years prior to and the 3 years following introduction of the new CHEP process. To control for temporal changes in the incidence of other cardiovascular conditions for which antihypertensive agents may be prescribed for their non-blood pressure-lowering effects (for example, angiotensin-converting enzyme (ACE) inhibitors for heart failure or coronary artery disease), prescription rates for digoxin, loop diuretics, and nitrates were also examined. RESULTS: Prescriptions for all antihypertensive agents increased significantly between 1996 and 2001 [11% for thiazides, 45% for beta-blockers, 68% for ACE inhibitors, 19% for calcium channel blockers, and 4332% for angiotensin receptor blockers (ARBs)]. Loop diuretic prescriptions increased 27%, but prescriptions for digoxin (-19%) and nitrates (-8%) declined over this time frame. Time series analyses demonstrated increases in the prescription growth rate for all four antihypertensive drug classes recommended in CHEP for the period 1999-2001 compared with 1996-1998, which were statistically significantly and of substantial magnitude (absolute annual increase in prescription growth rate of 4.6% (95% confidence interval 3.5-5.9%) for thiazides, 3.0% (1.8-4.2%) for beta-blockers, 8.2% (6.7-9.7%) for ACE inhibitors, and 6.1% (4.4-7.8%) for calcium channel blockers). The growth rate in nitrate prescriptions did not significantly change [1.1% (-0.6 to +3.0%)] and, although the changes in growth rate for loop diuretics [4.7% (3.2-6.3%)] and digoxin [2.1% (0.6-3.5%)] were statistically significant, they were of smaller magnitude than the changes in the four recommended antihypertensive agents. Similar results were observed when analysis was restricted to new prescriptions only. CONCLUSIONS: Prescriptions for all antihypertensive drugs increased substantially in Canada between 1996 and 2001; the rate of increase was significantly greater after 1999 for all four drugs recommended as first-line therapy in the annual CHEP guidelines. This preliminary data is encouraging, but a national survey of blood pressure control is needed to fully evaluate the impact of the new Canadian guideline process.

Providing evidence-based information to patients in general practice and pharmacies: what is the acceptability, usefulness and impact on drug use?

BACKGROUND: A common and often integral method of delivering patient information is the use of patient guides. However, the acceptability, utility and impact of evidence-based therapeutic guides on physicians, pharmacists and patients have not been well evaluated. METHODS: This study was a prospective evaluation of 53 general practitioners' offices and 30 community pharmacies from three locations in Canada. Evidence-based guides were provided to 1176 patients who presented to either a general practitioner or a community pharmacist and were interested in receiving information about sore throat, heartburn, or osteoporosis (http://www.ti.ubc.ca/canadadrugguide). The acceptability, utility and impact of the guides were assessed via structured patient telephone interviews, structured health professional interviews, and patient chart audits. RESULTS: Eighty to 90% of patients reported that the guides were 'very easy' to understand. Fifty six per cent/47%/38% (sore throat/heartburn/osteoporosis) of patients rated the guides as 'very' or 'extremely' useful. Seventy-two per cent/67%/58% of respondents reported that the information helped them make decisions about their treatment. Ninety eight per cent of physicians and 92% of pharmacists reported that the guides helped their patients understand the issues involved in their treatment. None of the analyses showed any significant differences in prescribing of medications between the intervention and control groups. INTERPRETATIONS: Patients found these evidence-based guides to be useful, easy to understand, and that they helped them in their understanding of treatment options and the decision-making process. Physicians and pharmacists reported that the guides helped their patients understand the issues involved in their treatment. Further research is required to determine the degree to which providing evidence-based guides to patients can impact on prescribing and patient outcomes.

What patients want to know about their medications. Focus group study of patient and clinician perspectives.

OBJECTIVE: To describe what patients want to know about their medications and how they currently access information. To describe how physicians and pharmacists respond to patients' information needs. To use patients', physicians', and pharmacists' feedback to develop evidence-based treatment information sheets. DESIGN: Qualitative study using focus groups and a grounded-theory approach. SETTING: Three regions of Canada (British Columbia, Nova Scotia, and Ontario). PARTICIPANTS: Eighty-eight patients, 27 physicians, and 35 pharmacists each took part in one of 19 focus groups. METHOD: Purposeful and convenience sampling was used. A trained facilitator used a semistructured interview guide to conduct the focus groups. Analysis was completed by at least two research-team members. MAIN FINDINGS: Patients wanted both general and specific information when considering medication treatments. They wanted basic information about the medical condition being treated and specific information about side effects, duration of treatment, and range of available treatment options. Physicians and pharmacists questioned the amount of side-effect and safety information patients wanted and thought that too much information might deter patients from taking their medications. Patients, physicians, and pharmacists supported the use of evidence-based treatment information sheets. CONCLUSION: Patients and clinicians each appear to have a different understanding of what and how much information patients should receive about medications. Feedback from patients can be used to develop patient-oriented treatment information.