Evaluation of a multicomponent intervention consisting of education and feedback to reduce benzodiazepine prescriptions by general practitioners: The BENZORED hybrid type 1 cluster randomized controlled trial.

BACKGROUND: Current benzodiazepine (BZD) prescription guidelines recommend short-term use to minimize the risk of dependence, cognitive impairment, and falls and fractures. However, many clinicians overprescribe BZDs and chronic use by patients is common. There is limited evidence on the effectiveness of interventions delivered by general practitioners (GPs) on reducing prescriptions and long-term use of BZDs. We aimed to evaluate the effectiveness of a multicomponent intervention for GPs that seeks to reduce BZD prescriptions and the prevalence of long-term users. METHODS AND FINDINGS: We conducted a multicenter two-arm, cluster randomized controlled trial in 3 health districts in Spain (primary health centers [PHCs] in Balearic Islands, Catalonia, and Valencian Community) from September 2016 to May 2018. The 81 PHCs were randomly allocated to the intervention group (n = 41; 372 GPs) or the control group (n = 40; 377 GPs). GPs were not blinded to the allocation; however, pharmacists, researchers, and trial statisticians were blinded to the allocation arm. The intervention consisted of a workshop about the appropriate prescribing of BZDs and tapering-off long-term BZD use using a tailored stepped dose reduction with monthly BZD prescription feedback and access to a support web page. The primary outcome, based on 700 GPs (351 in the control group and 349 in the intervention group), compared changes in BZD prescriptions in defined daily doses (DDDs) per 1,000 inhabitants per day after 12 months. The 2 secondary outcomes were the proportion of long-term users (≥6 months) and the proportion of long-term users over age 65 years. Intention-to-treat (ITT) analysis was used to assess all clinical outcomes. Forty-nine GPs (21 intervention group and 28 control group) were lost to follow-up. However, all GPs were included in the ITT analysis. After 12 months, there were a statistically significant decline in total BZD prescription in the intervention group compared to the control group (mean difference: -3.24 DDDs per 1,000 inhabitants per day, 95% confidence interval (CI): -4.96, -1.53, p < 0.001). The intervention group also had a smaller number of long-term users. The adjusted absolute difference overall was -0.36 (95% CI: -0.55, -0.16, p > 0.001), and the adjusted absolute difference in long-term users over age 65 years was -0.87 (95% CI: -1.44, -0.30, p = 0.003). A key limitation of this clustered design clinical trial is the imbalance of some baseline characteristics. The control groups have a higher rate of baseline BZD prescription, and more GPs in the intervention group were women, GPs with a doctorate degree, and trainers of GP residents. CONCLUSIONS: A multicomponent intervention that targeted GPs and included educational meeting, feedback about BZD prescriptions, and a support web page led to a statistically significant reduction of BZD prescriptions and fewer long-term users. Although the effect size was small, the high prevalence of BZD use in the general population suggests that large-scale implementation of this intervention could have positive effects on the health of many patients. TRIAL REGISTRATION: ISRCTN ISRCTN28272199.

Evaluating the Implementation of a Multicomponent Intervention Consisting of Education and Feedback on Reducing Benzodiazepine Prescriptions by General Practitioners: BENZORED Hybrid Type I Cluster Randomized Controlled Trial.

BACKGROUND: General practitioners (GPs) in developed countries widely prescribe benzodiazepines (BZDs) for their anxiolytic, hypnotic, and muscle-relaxant effects. Treatment duration, however, is rarely limited, and this results in a significant number of chronic users. Long-term BZD use is associated with cognitive impairment, falls with hip fractures, traffic accidents, and increased mortality. The BENZORED IV trial was a hybrid type-1 trial conducted to evaluate the effectiveness and implementation of an intervention to reduce BZD prescription in primary care. The purpose of this qualitative study was to analyze the facilitators and barriers regarding the implementation of the intervention in primary care settings. METHODS: A qualitative interview study with 40 GPs from three Spanish health districts. Focus group meetings with GPs from the intervention arm of the BENZORED IV trial were held at primary healthcare centers in the three districts. For sampling purposes, the GPs were classified as high or low implementers according to the success of the intervention measured at 12 months. The Consolidated Framework for Implementation Research (CFIR) was used to conduct the meetings and to code, rate, and analyze the data. RESULTS: Three of the 41 CFIR constructs strongly distinguished between high and low implementers: the complexity of the intervention, the individual Stage of Change, and the key stakeholder's engagement. Seven constructs weakly discriminated between the two groups: adaptability in the intervention, external policy and incentives, implementation climate, relative priority, self-efficacy, compatibility, and engaging a formally appointed implementation leader. Fourteen constructs did not discriminate between the two groups, six had insufficient data for evaluation, and eleven had no data for evaluation. CONCLUSIONS: We identified constructs that could explain differences in the efficacy in implementation of the intervention. This information is relevant for the design of successful strategies for implementation of the intervention.

Comparative Cost Analysis Of Intravenous And Subcutaneous Administration Of Rituximab In Lymphoma Patients.

PURPOSE: The availability of different routes of administration of rituximab, with different dosing and times of infusion in the day care unit, raises the question of which formulation would be the best in terms of direct cost, particularly with the approval of new intravenous (IV) rituximab biosimilars. We aim to retrospectively compare the direct costs of IV and subcutaneous (SC) rituximab in lymphoma, considering drug cost, pharmacy handling and occupation in day care unit in Son Espases University Hospital during 2017, now that the IV biosimilar is available. PATIENTS AND METHODS: The data were collected from Oncosafety®-AVIDA for doses and SAP® for economic data. The costs of occupation are published by the Local Health Service. RESULTS: In 2017, 527 cycles were prescribed for 103 patients with lymphoma: 141 IV and 386 SC. Median doses were 690 mg and 1400 mg with a median cost of the drug of 1458.45€ and 1334.77€ for IV and SC routes, respectively. The nurse handling costs were 4.49€ and 2.24€, respectively. The cost of the day care unit occupation was 493€ and 123€, respectively. Overall, the median total cost per cycle was 1955.94€ for the IV, 1460.01€ for the SC and 1729€ for the biosimilar (p<0.001). The sensitivity analysis showed that it would be necessary for the cost of the IV biosimilar to be 34% lower than the price of SC rituximab to make a difference. CONCLUSION: This study shows a reduction in the cost with the administration of SC rituximab in real life compared with using the IV original rituximab and the biosimilar. This information is relevant for healthcare managers and administrations and applies only in the case of drugs with SC original presentations still not available in their correspondent biosimilars.

Intervention to reduce benzodiazepine prescriptions in primary care, study protocol of a hybrid type 1 cluster randomised controlled trial: the BENZORED study.

INTRODUCTION: Benzodiazepines (BZDs) are mainly used to treat anxiety and sleep disorders, and are often prescribed for long durations, even though prescription guidelines recommend short-term use due to the risk of dependence, cognitive impairment, and falls and fractures. Education of general practitioners (GPs) regarding the prescription of BZDs may reduce the overuse and of these drugs.The aims of this study are to analyse the effectiveness of an intervention targeted to GPs to reduce BZD prescription and evaluate the implementation process. METHODS AND ANALYSIS: The healthcare centres in three regions of Spain (Balearic Islands, Catalonia and Community of Valencia) will be randomly allocated to receive a multifactorial intervention or usual care (control). GPs in the intervention group will receive a 2-hour workshop about best-practice regarding BZD prescription and BZD deprescribing, monthly feedback about their BZD prescribing practices and access to a support web page. Outcome measures for each GP are the defined daily dosage per 1000 inhabitants per day and the proportion of long-term BZD users at 12 months. Data will be collected from the electronic prescription database of the public health system, and will be subjected to intention-to-treat analysis. Implementation will be evaluated by mixed methods following the five domains of the Consolidated Framework For Implementation Research. ETHICS AND DISSEMINATION: This study was approved by the Balearic Islands Ethical Committee of Clinical Research (IB3065/15), l'IDIAP Jordi Gol Ethical Committee of Clinical Research (PI 15/0148) and Valencia Primary Care Ethical Committee of Clinical Research (P16/024). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN28272199.