How pharmacoepidemiology networks can manage distributed analyses to improve replicability and transparency and minimize bias

Several pharmacoepidemiology networks have been developed over the past decade that use a distributed approach, implementing the same analysis at multiple data sites, to preserve privacy and minimize data sharing. Distributed networks are efficient, by interrogating data on very large populations. The structure of these networks can also be leveraged to improve replicability, increase transparency, and reduce bias. We describe some features of distributed networks using, as examples, the Canadian Network for Observational Drug Effect Studies, the Sentinel System in the USA, and the European Research Network of Pharmacovigilance and Pharmacoepidemiology. Common protocols, analysis plans, and data models, with policies on amendments and protocol violations, are key features. These tools ensure that studies can be audited and repeated as necessary. Blinding and strict conflict of interest policies reduce the potential for bias in analyses and interpretation. These developments should improve the timeliness and accuracy of information used to support both clinical and regulatory decisions

Adjusting for Confounding in Early Postlaunch Settings: Going beyond Logistic Regression Models

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Background: Postlaunch data on medical treatments can be analyzed to explore adverse events or relative effectiveness in real-life settings. These analyses are often complicated by the number of potential confounders and the possibility of model misspecification. Methods: We conducted a simulation study to compare the performance of logistic regression, propensity score, disease risk score, and stabilized inverse probability weighting methods to adjust for confounding. Model misspecification was induced in the independent derivation dataset. We evaluated performance using relative bias confidence interval coverage of the true effect, among other metrics. Results: At low events per coefficient (1.0 and 0.5), the logistic regression estimates had a large relative bias (greater than-100%). Bias of the disease risk score estimates was at most 13.48% and 18.83%. For the propensity score model, this was 8.74% and >100%, respectively. At events per coefficient of 1.0 and 0.5, inverse probability weighting frequently failed or reduced to a crude regression, resulting in biases of-8.49% and 24.55%. Coverage of logistic regression estimates became less than the nominal level at events per coefficient ≤5. For the disease risk score, inverse probability weighting, and propensity score, coverage became less than nominal at events per coefficient ≤2.5, ≤1.0, and ≤1.0, respectively. Bias of misspecified disease risk score models was 16.55%. Conclusion: In settings with low events/exposed subjects per coefficient, disease risk score methods can be useful alternatives to logistic regression models, especially when propensity score models cannot be used. Despite better performance of disease risk score methods than logistic regression and propensity score models in small events per coefficient settings, bias, and coverage still deviated from nominal

Proefmelkstal geeft inzicht in melkafgifte

De opvatting dat de koe zich moet aanpassen aan de melktechniek is achterhaald. De melktechniek moet in dienst staan van de koe. Sturing van het melkproces volgens dit uitgangspunt, zal de melkafgifte en de uiergezondheid verbeteren. Met de huidige kennis en de melktechnische mogelijkheden, is het mogelijk om diergericht te kunnen melken

Reinigen in compartimenten werkt kostenbesparend

Door de melkleidinginstallatie tijdens de reiniging te verdelen in compartimenten is tot 40% op de hoeveelheid water, energie en chemicaliën te besparen

Comfort stalmatten bepaalt verschillen

. In dit onderzoek zijn daarom vier verschillende typen stalmatten vergeleken op basis van de bijdrage aan de hygiëne van de uier, spenen en melk. Het blijkt dat de matten alleen verschillen in het comfort dat wordt geboden

Milieuvriendelijke melkkoeling op de boerderij

Natuurlijke koolwaterstoffen zijn goed bruikbaar als koelmiddel in melkkoeltanks. De invloed op het broeikaseffect is nihil en het energieverbruik van dit koelsysteem lijkt gunstiger dan huidige systemen

Houd de reiniging onder controle

Het resultaat van iedere reiniging van melkleidinginstallatie en melkkoeltank wordt bepaald door de welbekende factoren dosering, temperatuur, mechanische werking, tijdsduur en de mens. Zonder afstemming op elkaar, zal dit in de praktijk resulteren ineen verhoogd kiemgeta

Vriespunt van melk varieert per dag

Het vriespunt van melk is lager dan dat van water; gemiddeld -0,520 C in Nederlandse tankmelk. Problemen met het vriespunt worden meestal veroorzaakt door watertoevoeging. Wordt een afwijkend vriespunt in de tankmelk echter niet door extra water veroorzaakt, dan zal op dierniveau verder gezocht moeten worden. Op dierniveau is de invloed van het lactatiestadium op het vriespunt van koemelk aangetoond. Verder zijn er verschillen tussen ochtendmelk en avondmelk. Dit zijn de belangrijkste conclusies van uitgevoerd vriespuntonderzoek op de Waiboerhoeve

Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/-stanols in humans

<p>Abstract</p> <p>Background</p> <p>To examine the effects on LDL cholesterol of the combined use of statins and phytosterols/-stanols, in vivo studies and clinical trials are necessary. However, for a better interpretation of the experimental data as well as to possibly predict cholesterol levels given a certain dosing regimen of statins and phytosterols/-stanols a more theoretically based approach is helpful. This study aims to construct a mathematical model to simulate reductions in low-density lipoprotein (LDL) cholesterol in persons who combine the use of statins with a high intake of phytosterols/-stanols, e.g. by the use of functional foods.</p> <p>Methods and Results</p> <p>The proposed model includes the cholesterol pool size in the liver and serum levels of very low-density lipoprotein (VLDL) cholesterol. Both an additional and a multiplicative effect of phytosterol/-stanol intake on LDL cholesterol reduction were predicted from the model. The additional effect relates to the decrease of dietary cholesterol uptake reduction, the multiplicative effect relates to the decrease in enterohepatic recycling efficiency, causing increased cholesterol elimination through bile. From the model, it was demonstrated that a daily intake of 2 g phytosterols/-stanols reduces LDL cholesterol level by about 8% to 9% on top of the reduction resulting from statin use. The additional decrease in LDL cholesterol caused by phytosterol/-stanol use at the recommended level of 2 g/d appeared to be similar or even greater than the decrease achieved by doubling the statin dose.</p> <p>Conclusion</p> <p>We proposed a simplified mathematical model to simulate the reduction in LDL cholesterol after separate and combined intake of statins and functional foods acting on intestinal (re)absorption of cholesterol or bile acids in humans. In future work, this model can be extended to include more complex (regulatory) mechanisms.</p