A novel method for predicting the budget impact of innovative medicines:validation study for oncolytics

Background High budget impact (BI) estimates of new drugs have led to decision-making challenges potentially resulting in restrictions in patient access. However, current BI predictions are rather inaccurate and short term. We therefore developed a new approach for BI prediction. Here, we describe the validation of our BI prediction approach using oncology drugs as a case study. Methods We used Dutch population-level data to estimate BI where BI is defined as list price multiplied by volume. We included drugs in the antineoplastic agents ATC category which the European Medicines Agency (EMA) considered a New Active Substance and received EMA marketing authorization (MA) between 2000 and 2017. A mixed-effects model was used for prediction and included tumor site, orphan, first in class or conditional approval designation as covariates. Data from 2000 to 2012 were the training set. BI was predicted monthly from 0 to 45 months after MA. Cross-validation was performed using a rolling forecasting origin with e|Ln(observed BI/predicted BI)| as outcome. Results The training set and validation set included 25 and 44 products, respectively. Mean error, composed of all validation outcomes, was 2.94 (median 1.57). Errors are higher with less available data and at more future predictions. Highest errors occur without any prior data. From 10 months onward, error remains constant. Conclusions The validation shows that the method can relatively accurately predict BI. For payers or policymakers, this approach can yield a valuable addition to current BI predictions due to its ease of use, independence of indications and ability to update predictions to the most recent data

Determinants of DNA yield and purity collected with buccal cell samples

Buccal cells are an important source of DNA in epidemiological studies, but little is known about factors that influence amount and purity of DNA. We assessed these factors in a self-administered buccal cell collection procedure, obtained with three cotton swabs. In 2,451 patients DNA yield and in 1,033 patients DNA purity was assessed. Total DNA yield ranged from 0.08 to 1078.0 μg (median 54.3 μg; mean 82.2 μg ± SD 92.6). The median UV 260:280 ratio, was 1.95. Samples from men yielded significantly more DNA (median 58.7 μg) than those from women (median 44.2 μg). Diuretic drug users had significantly lower purity (median 1.92) compared to other antihypertensive drug users (1.95). One technician obtained significantly lower DNA yields. Older age was associated with lower DNA purity. In conclusion, DNA yield from buccal swabs was higher in men and DNA purity was associated with age and the use of diuretics

Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries

Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39-49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed

Evaluation of patient outcomes in an area where prescribing of anticholinergic antidepressants was influenced by academic detailing

OBJECTIVE: To evaluate, on a patient level, the effect of a "physician-level intervention" that successfully reduced the incidence of anticholinergic antidepressant prescribing. DESIGN: Cross-sectional surveys with questionnaires sent before and after intervention. SETTING: Additional study in an RCT to reduce the prescribing of highly anticholinergic antidepressants in the elderly in the South Holland Islands. PARTICIPANTS: Elderly patients (age 60-95 years) who used antidepressants in 1995 and 1996 in our research area according to a health insurance prescription database. MAIN OUTCOME MEASURES: Prevalence of adverse events related to antidepressant use, severity of depression and quality of life were compared in users living in the intervention and control areas. RESULTS: Prior to our intervention we sent 2,359 questionnaires of which we could use 827 (35%) for analysis. At baseline, there were no statistically significant differences between the intervention and control areas. After the intervention 3,375 questionnaires were sent, of which 939 (28%) could be used. The occurrence of "dry mouth" and "coughing" and the "amount of pain" were lower in the intervention area compared to the control area (p < 0.05). CONCLUSION: We found no indications that adverse events, severity of depression or quality of life were changed in an unfavourable direction, when comparing patients inside and outside the intervention area