Analyzing generic and branded substitution patterns in the Netherlands using prescription data

BACKGROUND: As in other societies, pharmaceutical expenditures in the Netherlands are rising every year. As a consequence, needs for cost control are often expressed. One possible solution for cost control could come through increasing generic substitution by pharmacists. We aim to analyse the extent and nature of substitution in recent years and estimate the likelihood of generic or branded substitution in Dutch pharmacies in relation to various characteristics. METHODS: We utilized a linked prescription dataset originating from a general practitioner (GP) and a pharmacy database, both from the northern Netherlands. We selected specific drugs of interest, containing about 55,000 prescriptions from 15 different classes. We used a crossed generalized linear mixed model to estimate the effects that certain patient and pharmacy characteristics as well as timing have on the likelihood that a prescription will eventually be substituted by the pharmacist. RESULTS: Generic substitution occurred at 25% of the branded prescriptions. Generic substitution was more likely to occur earlier in time after patent expiry and to patients that were older and more experienced in their drug use. Individually owned pharmacies had a lower probability of generic substitution compared to chain pharmacies. Oppositely, branded substitution occurred in 10% of generic prescriptions and was positively related to the patients' experience in branded use. Individually owned pharmacies were more likely to substitute a generic drug to a branded compared to other pharmacies. Antidepressant and PPI prescriptions were less prone to generic and more prone to branded substitution. CONCLUSION: Analysis of prescription substitution by the pharmacist revealed strong relations between substitution and patient experience on drug use, pharmacy status and timing. These findings can be utilised to design further strategies to enhance generic substitution

Non-steroidal or opioid analgesia use for children with musculoskeletal injuries (the No OUCH study): statistical analysis plan.

BACKGROUND: Pediatric musculoskeletal injuries cause moderate to severe pain, which should ideally be addressed upon arrival to the emergency department (ED). Despite extensive research in ED-based pediatric pain treatment, recent studies confirm that pain management in this setting remains suboptimal. The No OUCH study consist of two complementary, randomized, placebo-controlled trials that will run simultaneously for patients presenting to the ED with an acute limb injury and a self-reported pain score of at least 5/10, measured via a verbal numerical rating scale (vNRS). Caregiver/parent choice will determine whether patients are randomized to the two-arm or three-arm trial. In the two-arm trial, patients will be randomized to receive either ibuprofen alone or ibuprofen in combination with acetaminophen. In the three-arm trial, patients can also be randomized to a third arm where they would receive ibuprofen in combination with hydromorphone. This article details the statistical analysis plan for the No OUCH study and was submitted before the trial outcomes were available for analysis. METHODS/DESIGN: The primary endpoint of the No OUCH study is self-reported pain at 60 min, recorded using a vNRS. The principal safety outcome is the presence of any adverse event related to study drug administration. Secondary effectiveness endpoints include pain measurements using the Faces Pain Scale-Revised and the visual analog scale, time to effective analgesia, requirement of a rescue analgesic, missed fractures, and observed pain reduction using different definitions of successful analgesia. Secondary safety outcomes include sedation measured using the Ramsay Sedation Score and serious adverse events. Finally, the No OUCH study investigates the reasons given by the caregiver for selecting the two-arm (Non-Opioid) or three-arm (Opioid) trial, caregiver satisfaction, physician preferences for analgesics, and caregiver comfort with at-home pain management. DISCUSSION: The No OUCH study will inform the relative effectiveness of acetaminophen and hydromorphone, in combination with ibuprofen, and ibuprofen alone as analgesic agents for patients presenting to the ED with an acute musculoskeletal injury. The data from these trials will be analyzed in accordance with this statistical analysis plan. This will reduce the risk of producing data-driven results and bias in our reported outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03767933 . Registered on December 7, 2018

Multi-dose Oral Ondansetron for Pediatric Gastroenteritis: study Protocol for the multi-DOSE oral ondansetron for pediatric Acute GastroEnteritis (DOSE-AGE) pragmatic randomized controlled trial

BACKGROUND: There are limited treatment options that clinicians can provide to children presenting to emergency departments with vomiting secondary to acute gastroenteritis. Based on evidence of effectiveness and safety, clinicians now routinely administer ondansetron in the emergency department to promote oral rehydration therapy success. However, clinicians are also increasingly providing multiple doses of ondansetron for home use, creating unquantified cost and health system resource use implications without any evidence to support this expanding practice. METHODS/DESIGN: DOSE-AGE is a randomized, placebo-controlled, double-blinded, six-center, pragmatic clinical trial being conducted in six Canadian pediatric emergency departments (EDs). In September 2019 the study began recruiting children aged 6 months to 18 years with a minimum of three episodes of vomiting in the 24 h preceding enrollment,(1:1 allocation via an internet-based, third-party, randomization service) to receive a 48-h supply (i.e., six doses) of ondansetron oral solution or placebo, administered on an as-needed basis. All participants, caregivers and outcome assessors will be blinded to group assignment. Outcome data will be collected by surveys administered to caregivers 24, 48 and 168 h following enrollment. The primary outcome is the development of moderate-to-severe gastroenteritis in the 7 days following the ED visit as measured by a validated clinical score (the Modified Vesikari Scale). Secondary outcomes include duration and frequency of vomiting and diarrhea, proportions of children experiencing unscheduled health care visits and intravenous rehydration, caregiver satisfaction with treatment and safety. A preplanned economic evaluation will be conducted alongside the trial. DISCUSSION: Definitive data are lacking to guide the clinical use of post-ED visit multidose ondansetron in children with acute gastroenteritis. Usage is increasing, despite the absence of supportive evidence. The incumbent additional costs associated with use, and potential side effects such as diarrhea and repeat visits, create an urgent need to evaluate the effect and safety of multiple doses of ondansetron in children focusing on post-emergency department visit and patient-centered outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03851835. Registered on 22 February 2019