A Pharmaceutical Care Program to Improve Adherence to Statin Therapy:A Randomized Controlled Trial

BACKGROUND: Despite the well-known beneficial effects of statins, many patients do not adhere to chronic medication regimens. OBJECTIVE: To implement and assess the effectiveness of a community pharmacy based pharmaceutical care program developed to improve patients' adherence to statin therapy. METHODS: An open-label, prospective, randomized controlled trial was conducted at 26 community pharmacies in the Netherlands. New users of statins who were aged 18 years or older were randomly assigned to receive either usual care or a pharmacist intervention. The intervention consisted of 5 individual counseling sessions by a pharmacist during a 1-year period. During these sessions, patients received structured education about the importance of medication adherence, lipid levels were measured, and the association between adherence and lipid levels was discussed. Adherence to statin therapy was assessed as discontinuation rates 6 and 12 months after statin initiation, and as the medication possession ratio (MPR), and compared between the pharmaceutical care and usual care groups. RESULTS: A total of 899 subjects (439 in the pharmaceutical care group and 460 in the usual care group) were evaluable for effectiveness analysis. The pharmaceutical care program resulted in a significantly lower rate of discontinuation within 6 months after initiating therapy versus usual care (HR 0.66, 95% Cl 0.46 to 0.96). No significant difference between groups was found in discontinuation at 12 months (HR 0.84, 95% Cl 0.65 to 1.10). Median MPR was very high (>99%) in both groups and did not differ between groups. CONCLUSIONS: These results demonstrate the feasibility and effectiveness of a community pharmacy based pharmaceutical care program to improve medication adherence in new users of statins. Frequent counseling sessions (every 3 months) are necessary to maintain the positive effects on discontinuation. Although improvements are modest, the program can be applied easily to a larger population and have a large impact, as the interventions are relatively inexpensive and easy to, implement in clinical practice

Pre-approval and post-approval availability of evidence and clinical benefit of conditionally approved cancer drugs in Europe: a comparison with standard approved cancer drugs

Aims: Cancer drugs are increasingly approved through expedited regulatory pathways including the European conditional marketing authorization (CMA). Whether, when taking CMA post-approval confirmatory trials into account, the level of evidence and clinical benefit between CMA and standard approved (SMA) drugs differs remains unknown. Methods: We identified all CMA cancer indications converted to SMA in 2006–2020 and compared these to similar SMA indications with regard to pivotal trial and CMA post-approval confirmatory trial design, outcomes and demonstrated clinical benefit (per the European Society for Medical Oncology Magnitude of Clinical Benefit Scale). We tested for differences in clinical benefit and whether substantial clinical benefit was demonstrated. To account for the clinical benefit of unconverted CMA indications, we performed sensitivity analyses. Results: We included 15 SMA and 15 converted CMA cancer indications (17 remained unconverted). Approval of 11 SMA (73%) and four CMA indications (27%) was supported by a controlled trial. Improved overall survival (OS) was demonstrated for four SMA indications (27%). Improved quality of life (QoL) was demonstrated for three SMA (20%) and one CMA indication(s) (7%). Of subsequent CMA post-approval confirmatory trials, 11 were controlled (79%), one demonstrated improved OS (7%) and five improved QoL (36%). After conversion, CMA indications were associated with similar clinical benefit (P =.31) and substantial clinical benefit as SMA indications (risk ratio 1.4, 95% confidence interval 0.57–3.4). Conclusion: While CMA cancer indications are initially associated with less comprehensive evidence than SMA indications, levels of evidence and clinical benefit are similar after conversion from CMA to SMA

Improving pharmacotherapy after myocardial infarction by group academic detailing using feedback data on a patient level

STUDY OBJECTIVE: To develop and evaluate a peer review group (PRG) meeting using feedback data on a patient level to improve the quality of drug therapy for prevention of recurrent myocardial infarction. DESIGN: Prospective follow-up study. DATA SOURCE: General practitioners' computerized patients records (intervention patients) and the PHARMO record linkage system (controls). PATIENTS: Forty patients in the intervention group and 1030 control patients; both groups had documented myocardial infarction. INTERVENTION: The intervention, which was based on the principles of group academic detailing, consisted of scoring current cardiovascular treatment on separate forms for each patient, presenting an overview of, and discussing, evidence-based treatment after myocardial infarction, defining the target population, formulating a binding consensus, and identifying patients who were eligible for improvement of pharmacotherapy. MEASUREMENTS AND MAIN RESULTS: Drug therapy and adherence to the newly formulated PRG consensus were assessed at baseline and 1 year after the intervention. Of the patients who received the intervention and were not treated according to the PRG consensus at baseline, 40% received treatment according to the consensus 12 months after the PRG meeting. In the control group, the proportion of patients was 9.5% (prevalence ratio 4.2, 95% confidence interval 1.8-9.7). CONCLUSION: Peer review group meetings can be a valuable tool for improving pharmacotherapy after myocardial infarction

Preventive drug use in patients with a history of nonfatal myocardial infarction during 12-year follow-up in The Netherlands : a retrospective analysis

BACKGROUND: Myocardial infarction (MI) is a common cause of death in developed countries. Long-term preventive pharmacotherapy has been shown to decrease mortality and morbidity after MI. Based on a literature search, studies of these therapies to date have estimated the use of monotherapy, whereas many patients are prescribed combination therapy. Thus, assessment of long-term combination drug use after MI is timely. OBJECTIVE: The aim of this study was to assess the use of oral antithrombotics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, hydroxymethyl-glutaryl coenzyme A reductase inhibitors ("statins"), and their combinations after MI at discharge and during 12-year follow-up. METHODS: This community-based, retrospective data analysis was conducted at Utrecht University, Utrecht, The Netherlands. Data from patients aged > or =18 years at hospital admission who experienced nonfatal acute MI between 1991 and 2000 and had a duration of follow-up > or =30 days were included in the analysis. Data were retrieved from the Pharmo Record Linkage System database, which links pharmacies' dispensation records to hospitals' discharge records on an individual patient level, allowing the investigator to observe individual patients' medication use over time. Primary outcome measures were the use of preventive medicines (oral antithrombotics, beta-blockers, ACE inhibitors, and statins) at discharge, overall use, and persistence during 12-year follow-up. RESULTS: Of 330,000 patients in the database, 4007 were included in the analysis (2828 men, 1179 women; mean [SD] age, 63.5 [12.5] years). Use at discharge and overall use of oral antithrombotics and statins increased significantly between 1991 and 2000, whereas use of beta-blockers and ACE inhibitors increased mainly in patients discharged in the latter years of the follow-up period. Therapy with any combination of drugs increased strikingly from 1991 to 2000, from 47% to 90%. At 1 year after discharge, 32% of patients had discontinued their first-prescribed combination treatments. At 5 years after discharge, this rate increased to 57%, suggesting a low rate of persistence CONCLUSIONS: Based on the results of this retrospective data analysis, the use of MI-preventive drug treatment at and after discharge increased significantly in this population in The Netherlands during the 1990s. Combination therapy increased strikingly. However, persistence with combination therapy was low

Effect of drug combinations on admission for recurrent myocardial infarction

OBJECTIVE: To determine the effect of the number of different drugs with adherence to medication of at least 70% on recurrent admission for myocardial infarction (MI) in patients with a history of MI. DESIGN: Nested case-control study in a dynamic cohort. SETTING: PHARMO database that contains pharmacy dispensing records and hospital discharge records of 350,000 Dutch citizens. SUBJECTS: All patients admitted to hospital for first MI (ICD-9 410) from 1991 to 2000 with at least a 30-day survival after admission. Cases were admitted for recurrent MI and were matched for age, sex, and year of admission with controls who did not have a recurrent MI. MAIN OUTCOME MEASURE(S): Odds ratio with 95% CI for admission for recurrent MI. Exposure was the number of preventive drugs (antiplatelet agents, statins and beta blockers or ACE inhibitors) used for at least 70% of the time. RESULTS: 389 cases were matched with 2344 controls. The use of one drug was associated with a 6% odds reduction (95% CI 30% reduction to 28% increase) for admission for recurrent MI. The use of two or three drugs was associated with reductions of 26% and 41% (47% reduction to 3% increase and 6% to 63% reduction, respectively). Addition of one drug caused a 16% reduction (4% to 26%). CONCLUSIONS: Multiple drug treatment decreases admissions for recurrent MI in patients with a history of MI. Every addition of a drug, regardless of drug class, reduces the risk even further. These results support the treatment strategies as applied in daily practice

Oral Antithrombotic Use Among Myocardial Infarction Patients

OBJECTIVE: To examine the use of oral antithrombotics (i.e., antiplatelet agents, oral anticoagulants) after myocardial infarction (MI) in the Netherlands from 1988 to 1998. METHODS: Retrospective follow-up of 3800 patients with MI, using data from the PHARMO Record Linkage System. RESULTS: From 1988 to 1998, oral antithrombotic treatment increased significantly from 54.0% to 88.9%. In 1998, only 75.8% of patients who experienced a MI in the late 1980s received oral antithrombotic treatment compared with 94.4% of those who experienced a recent MI. CONCLUSIONS: Oral antithrombotics were considerably underused in patients with a past history of MI. Therefore, these patients should be reviewed for antithrombotic therapy to assess whether their failure to use oral antithrombotics was right or wrong, and whether treatment should be initiated if possible

Comprehensive evaluation of post-approval regulatory actions during the drug lifecycle–a focus on benefits and risks

Background: Prior studies investigated regulatory actions that reflected a negative impact on drug risks. We aimed to evaluate occurrence of regulatory actions that reflected a negative or positive impact on benefits or risks, as well as relations between them. Research design and methods: We followed EMA-approved innovative drugs from approval (2009–2010) until July 2020 or withdrawal to identify regulatory actions. We assessed these for impact on benefits or risks and relations between actions. Additionally, we scrutinized drug lifecycles for time-variant characteristics that may contribute to specific patterns of regulatory actions. Results: We identified 14 letters and 361 label updates for 40 drugs. Of the label updates, 85 (24%) reflected a positive impact, mostly concerning indications, and 276 (76%) a negative impact, mostly adverse drug reactions. Many updates (54%) occurred simultaneously with other updates, also if these reflected a different impact. Furthermore, levels of patient exposure, innovativeness, needs for regulatory learning and unexpected risks may contribute to patterns of regulatory actions. Conclusions: Almost a quarter of regulatory actions reflected a positive impact on benefits and risks. Also, simultaneous learning about benefits and risks suggests an important role for drug development in risk characterization. These findings may impact regulatory analyses and decision-making

Improving pharmacotherapy after myocardial infarction by group academic detailing using feedback data on a patient level

STUDY OBJECTIVE: To develop and evaluate a peer review group (PRG) meeting using feedback data on a patient level to improve the quality of drug therapy for prevention of recurrent myocardial infarction. DESIGN: Prospective follow-up study. DATA SOURCE: General practitioners' computerized patients records (intervention patients) and the PHARMO record linkage system (controls). PATIENTS: Forty patients in the intervention group and 1030 control patients; both groups had documented myocardial infarction. INTERVENTION: The intervention, which was based on the principles of group academic detailing, consisted of scoring current cardiovascular treatment on separate forms for each patient, presenting an overview of, and discussing, evidence-based treatment after myocardial infarction, defining the target population, formulating a binding consensus, and identifying patients who were eligible for improvement of pharmacotherapy. MEASUREMENTS AND MAIN RESULTS: Drug therapy and adherence to the newly formulated PRG consensus were assessed at baseline and 1 year after the intervention. Of the patients who received the intervention and were not treated according to the PRG consensus at baseline, 40% received treatment according to the consensus 12 months after the PRG meeting. In the control group, the proportion of patients was 9.5% (prevalence ratio 4.2, 95% confidence interval 1.8-9.7). CONCLUSION: Peer review group meetings can be a valuable tool for improving pharmacotherapy after myocardial infarction

The Role of Regulator-Imposed Post-Approval Studies in Health Technology Assessments for Conditionally Approved Drugs

BACKGROUND: The European Medicines Agency (EMA) aims to resolve uncertainties associated with conditionally approved drugs by imposing post-approval studies. Results from these studies may be relevant for health technology assessment (HTA) organizations. This study investigated the role of regulator-imposed post-approval studies within HTA. METHODS: For all conditionally approved drugs up to December 2018, regulator-imposed post-approval studies were identified from EMA's public assessment reports. The availability for and inclusion of study results in relative effectiveness (re)assessments were analyzed for 4 European HTA organizations: NICE (National Institute for Health and Care Excellence, England/Wales), HAS (Haute Autorité de Santé, France), ZIN (Zorginstituut Nederland, the Netherlands) and the European Network for Health Technology Assessment (EUnetHTA, Europe). When study results became available between an HTA organization's initial assessment and reassessment, it was evaluated whether and how they affected the assessment and its outcome. RESULTS: For 36 conditionally approved drugs, 98 post-approval studies were imposed. In total, 81 initial relative effectiveness assessments (REAs) and 13 reassessments were available, with numbers of drugs (re)assessed varying greatly between jurisdictions. Study results were available for 16 initial REAs (20%) and included in 14 (88%), and available for 10 reassessments (77%) and included in all (100%). Five reassessments had an outcome different from the initial REA, with 4 (2 positive and 2 negative changes) relating directly to the new study results. Reassessments often cited the inability of post-approval studies to resolve the concerns reported in the initial REA. CONCLUSION: Results from regulator-imposed post-approval studies for conditionally approved drugs were not often used in REAs by HTA organizations, because they were often not yet available at the time of initial assessment and because reassessments were scarce. When available, results from post-approval studies were almost always used within HTA, and they have led to changes in conclusions about drugs' relative effectiveness. Post-approval studies can be relevant within HTA but the current lack of alignment between regulators and HTA organizations limits their potential