The reporting of p values, confidence intervals and statistical significance in Preventive Veterinary Medicine (1997-2017).

BACKGROUND: Despite much discussion in the epidemiologic literature surrounding the use of null hypothesis significance testing (NHST) for inferences, the reporting practices of veterinary researchers have not been examined. We conducted a survey of articles published in Preventive Veterinary Medicine, a leading veterinary epidemiology journal, aimed at (a) estimating the frequency of reporting p values, confidence intervals and statistical significance between 1997 and 2017, (b) determining whether this varies by article section and (c) determining whether this varies over time. METHODS: We used systematic cluster sampling to select 985 original research articles from issues published in March, June, September and December of each year of the study period. Using the survey data analysis menu in Stata, we estimated overall and yearly proportions of article sections (abstracts, results-texts, results-tables and discussions) reporting p values, confidence intervals and statistical significance. Additionally, we estimated the proportion of p values less than 0.05 reported in each section, the proportion of article sections in which p values were reported as inequalities, and the proportion of article sections in which confidence intervals were interpreted as if they were significance tests. Finally, we used Generalised Estimating Equations to estimate prevalence odds ratios and 95% confidence intervals, comparing the occurrence of each of the above-mentioned reporting elements in one article section relative to another. RESULTS: Over the 20-year period, for every 100 published manuscripts, 31 abstracts (95% CI [28-35]), 65 results-texts (95% CI [61-68]), 23 sets of results-tables (95% CI [20-27]) and 59 discussion sections (95% CI [56-63]) reported statistical significance at least once. Only in the case of results-tables, were the numbers reporting p values (48; 95% CI [44-51]), and confidence intervals (44; 95% CI [41-48]) higher than those reporting statistical significance. We also found that a substantial proportion of p values were reported as inequalities and most were less than 0.05. The odds of a p value being less than 0.05 (OR = 4.5; 95% CI [2.3-9.0]) or being reported as an inequality (OR = 3.2; 95% CI [1.3-7.6]) was higher in the abstracts than in the results-texts. Additionally, when confidence intervals were interpreted, on most occasions they were used as surrogates for significance tests. Overall, no time trends in reporting were observed for any of the three reporting elements over the study period. CONCLUSIONS: Despite the availability of superior approaches to statistical inference and abundant criticism of its use in the epidemiologic literature, NHST is substantially the most common means of inference in articles published in Preventive Veterinary Medicine. This pattern has not changed substantially between 1997 and 2017.

Budget impact model of rituximab after failure of one or more TNFalpha inhibitor therapies in the treatment of rheumatoid arthritis.

OBJECTIVES: To estimate the budget impact implied by the introduction of rituximab after failure of one or more anti-TNFalpha therapies in the perspective of the French health care system. METHODS: A Markov model reproduced the course, over 4years, of patients treated either by infliximab, etanercept, adalimumab or RTX, after failure of one or more anti-TNFalpha therapies, in a multicentric study. A sensitivity analysis was developed to account for patients in 3rd and subsequent lines of treatment who are expected to consume more healthcare resources. RESULTS: When RTX is not used, total annual medical cost is euro16,555 per patient, euro13,206 of which are dedicated to drug acquisition. When RTX is the only treatment in use, these costs decrease respectively to euro11,444 and euro7469. Total savings per patient and per year is euro5000. Over 4 years, total savings for the targeted population reach euro118M. In the sensitivity analysis, the difference between H2 and H2-coeff 2 (20%) reaches euro5,400,000 in total direct costs during the first year of simulation. This difference decreases along the period, to reach euro2,400,000 the fourth year of simulation, and is due to the fact that rituximab acquisition costs are independent from the treatment line. CONCLUSION: If TNFalpha inhibitors were the only treatment available, the annual global cost of treatment would be euro16,555 per patient versus euro11,444 for patients treated exclusively with rituximab. RTX is expected to produce important savings (-31%) if used after failure of one or more TNFalpha therapies. This is mainly due to its lower drug acquisition cost. These savings could increase with the development of rituximab in earlier stages of treatment.

Drotrecogin alfa's impact on intensive care workload in real life practice: a propensity score approach.

OBJECTIVES: To estimate the impact of drotrecogin alfa (DA) on intensive care workload in an observational study while illustrating the use of propensity score (PS) matching to control for recruitment bias. METHODS: PREMISS is a prospective, multicenter pre-post study. Its goal was to evaluate DA in the treatment of severe sepsis with multiple organ failure. Inclusions took place before (control patients) and after (DA-treated patients) the drug's market authorization. Workload was measured in euros using the French classification of medical procedures. It was compared between the groups via random effects gamma regression using two techniques: 1) regression adjusting for the patients' initial characteristics on the whole population; and 2) PS matching. A structural equation model was used to explore the pathways leading to a workload increase. RESULTS: Drotrecogin alfa is estimated to increase intensive care unit (ICU) workload by 20% (P = 0.045) according to the multivariate model and 34% (P = 0.002) according to the PS-matched one. In the structural equation model fitted, only DA's direct effect on the occurrence of bleeding events reaches significance (P = 0.024). CONCLUSIONS: We found a significant effect of DA on ICU workload with both standard methods of adjustment and PS matching. This effect appears to be mainly due to DA's effect on bleeding events. The analysis illustrated the usefulness of PS methods in the analysis of observational data, as it leads to conclusions similar to the traditional multivariate regression approaches while avoiding making too many adjustments, allowing focusing on the treatment effect.

Assessment of the cost effectiveness of travoprost versus latanoprost as single agents for treatment of glaucoma in France.

BACKGROUND AND OBJECTIVE: Control of intraocular pressure (IOP) is a major factor in avoiding visual impairment related to glaucoma. Both the cost and the effectiveness of therapy should be considered when initiating this lifelong treatment. The aim of this study was to assess the cost effectiveness of travoprost versus latanoprost as single agents for the treatment of glaucoma in France. METHODS: Two surveys, one documenting efficacy and the other costs, were used to provide data for a Markov model. The model reproduced the 5-year course of patients receiving a prostaglandin analogue, travoprost or latanoprost, as monotherapy. The effectiveness criterion was fitted with a Weibull distribution from a national study. Transition probabilities and costs per treatment line were extracted from two French observational databases. Bootstrap techniques were implemented to drive the probabilistic sensitivity analyses. The study compared both treatments given once daily as monotherapy to ambulatory patients with primary open-angle glaucoma or ocular hypertension. The main outcome measure was mean time to treatment change (MTTC). Possible treatment changes were the addition of adjunctive medication, treatment substitution, laser therapy or surgery. After laser therapy or surgery, patients could continue with no treatment or proceed to prostaglandin analogue as monotherapy or treatment substitution. IOP was stratified at treatment onset as < or =20, 21-23 and > or =24 mmHg, respectively. All costs were expressed in 2005 euros. RESULTS: MTTC was 44.3 months for travoprost and 37.8 for latanoprost. Additional 5-year costs for travoprost were euro51, resulting in an incremental cost-effectiveness ratio without treatment change of euro95 per year. Of patients treated with latanoprost, 1.9% underwent laser therapy or surgery, compared with 1.2% of patients treated with travoprost. The results differed with baseline IOP values, such that 55.6%, 53.9% and 50.4% of patients with pretreatment IOP values of < or =20, 21-23 and > or =24 mmHg, respectively, continued to receive travoprost treatment at 5 years, compared with 32.3%, 26.1% and 26.1% of patients, respectively, receiving latanoprost. Thus, incremental cost-effectiveness ratios (ICERs) without treatment change were euro140, euro45 and euro123 per year, respectively. CONCLUSION: Travoprost demonstrated a longer effectiveness profile than latanoprost and minimized early treatment changes. The smaller proportion of patients needing a new treatment, laser therapy or surgery virtually compensated for the higher travoprost acquisition cost. Overall, travoprost is cost effective compared with latanoprost, and is most cost effective in patients with pretreatment IOPs between 21 and 23 mmHg.

Cost-effectiveness of activated protein C in real-life clinical practice.

BACKGROUND: Recombinant human activated protein C (rhAPC) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal randomized trial. We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice. METHODS: We conducted a prospective observational study involving adult patients recruited before and after licensure of rhAPC in France. Inclusion criteria were applied according to the label approved in Europe. The expected recruitment bias was controlled by building a sample of patients matched for propensity score. Complete hospitalization costs were quantified using a regression equation involving intensive care units variables. rhAPC acquisition costs were added, assuming that all costs associated with rhAPC were already included in the equation. Cost comparisons were conducted using the nonparametric bootstrap method. Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio. RESULTS: In the initial cohort (n = 1096), post-license patients were younger, had less co-morbid conditions and had failure of more organs than did pre-license patients (for all: P < 0.0001). In the matched sample (n = 840) the mean age was 62.4 +/- 14.9 years, Simplified Acute Physiology Score II was 56.7 +/- 18.5, and the number of organ failures was 3.20 +/- 0.83. When rhAPC was used, 28-day mortality tended to be reduced (34.1% post-license versus 37.4% pre-license, P = 0.34), bleeding events were more frequent (21.7% versus 13.6%, P = 0.002) and hospital costs were higher (47,870 euros versus 36,717 euros, P < 0.05). The incremental cost-effectiveness ratios gained were as follows: 20,278 euros per life-year gained and 33,797 euros per quality-adjusted life-year gained. There was a 74.5% probability that rhAPC would be cost-effective if there were willingness to pay 50,000 euros per life-year gained. The probability was 64.3% if there were willingness to pay 50,000 euros per quality-adjusted life-year gained. CONCLUSION: This study, conducted in matched patient populations, demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay 50,000 euros per life-year gained is 74.5%.