Dataset Information

Case-crossover studies of therapeutics: design approaches to addressing time-varying prognosis in elderly populations.

ABSTRACT: Self-controlled analysis methods implicitly adjust for time-invariant confounding within individuals. A person's prognosis often varies over time and affects both therapy choice and subsequent health outcomes. Current approaches may not be able to fully address this within-person confounding. We evaluated the potential impact of time-varying prognosis in self-controlled studies of treatment effects and the extent to which alternative adjustment strategies could mitigate these biases.We used Medicare data linked to prescription drug data from a pharmaceutical assistance program to conduct case-crossover studies of the relationship between intermittent use of five classes of preventive medications (statins, oral hypoglycemics, antihypertensives, osteoporosis, and glaucoma medications) and death-relationships that are strongly biased because of healthy-user and sick-stopper effects. We used the case-case time-control design to adjust for confounding from exposure trends related to prognosis. Each class of medications was evaluated separately, with the remaining four used as reference drugs to estimate prognosis-related exposure trends.The case-crossover odds ratios were 0.39, 0.38, 0.40, 0.39, and 0.45 for statin, antihypertensive, glaucoma, hypoglycemic, and osteoporosis drugs, respectively. After adjusting for the estimated noncausal prognosis-related trends in drug exposure among all eligible cases, odds ratios were clustered closer to null (0.99, 0.95, 1.02, 0.99, and 1.16, respectively).Consideration of the sociology of medication use leading to health outcomes is essential in designing and analyzing self-controlled studies of treatment effects. Although the case-case time-control design was able to reduce bias from prognosis-related exposure trends in our examples, the difficulty in identifying appropriate reference exposures could be prohibitive.

SUBMITTER: Wang SV

PROVIDER: S-EPMC6092740 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Case-crossover studies of therapeutics: design approaches to addressing time-varying prognosis in elderly populations.

Wang Shirley V SV Gagne Joshua J JJ Glynn Robert J RJ Schneeweiss Sebastian S

Epidemiology (Cambridge, Mass.) 20130501 3

<h4>Background</h4>Self-controlled analysis methods implicitly adjust for time-invariant confounding within individuals. A person's prognosis often varies over time and affects both therapy choice and subsequent health outcomes. Current approaches may not be able to fully address this within-person confounding. We evaluated the potential impact of time-varying prognosis in self-controlled studies of treatment effects and the extent to which alternative adjustment strategies could mitigate these ...[more]

PMID: 23466528

Similar Datasets

Project description:BackgroundInfertility has become increasingly common worldwide. There is a need for the infertility literature to evaluate new interventions with IVF. The crossover design presents many methodological advantages for IVF trials. In addition to providing a within-person comparison of outcomes, it offers participants the opportunity to potentially benefit from more than one available treatment. However, infertility studies present a unique challenge in terms of bias: successful participants do not cross over to the second treatment group.ObjectivesThe main objective of our study was to survey the methodological features of crossover trials for infertility with in-vitro fertilization (IVF) based interventions. A secondary focus was reporting key results.Study design & settingWe conducted a methodological survey by systematically searching Medline and Embase databases. The capture-recapture technique was used to estimate the number of relevant studies that were not retrieved by our search strategy. We employed the Cochrane risk of bias tool to assess methodological rigour. Crossover-specific methods features were summarized. Treatment effects for pregnancy outcomes across studies are also presented.Results15 studies met inclusion criteria. Most studies were deemed to have high or unclear risks of bias, usually because of incomplete reporting of outcome data and assessment procedures. 13 studies did not employ crossover-specific methods to analyze outcome data by period, which may bias treatment effect estimates. Four studies reported pregnancy outcome data with sample sizes from both treatment periods. Of these four studies, three reported that the control intervention was favoured.ConclusionsThe main limitation of our survey was the small sample size of studies. Future reviews should be larger and seek to encompass a broader range of the infertility literature. Despite the issues identified in the included trials, consideration should still be given to using the crossover design in future infertility research. Employing crossover-specific analysis methods, such as accounting for participant non-completion, along with strict adherence to CONSORT reporting guidelines, may significantly reduce the risk of bias in individual studies.

Project description:ObjectivesThe goal of this study was to design and enable development of anticancer sulfonamides by coupling amines and dansyl chloride with strategically selected substituents. The synthesized structures were characterized by NMR and mass spectrometry. In addition, molecular docking analysis was used to determine the binding ability of sulfonamides toward 1AZM, a possible drug target, as compared with that of the well-known drug acetazolamide.MethodsSulfonamides were synthesized by coupling amines and dansyl chloride under highly favorable conditions. The designed sulfonamides incorporated strategically positioned substituents to impart diverse biological properties. The synthesized structures were validated with NMR and mass spectra. Molecular docking analysis was performed to evaluate the binding affinities of the synthesized sulfonamides with the potential drug target 1AZM.ResultsThe synthesis of sulfonamides through the coupling of amines and dansyl chloride was successfully achieved. The validation of the synthesized structures with NMR and mass spectra confirmed their chemical identities. Molecular docking analysis revealed that the synthesized sulfonamides displayed binding affinities ranging from -6.8 to -8.2 kcal/mol toward the potential drug target 1AZM. Importantly, all derivatives exhibited superior binding affinities to acetazolamide (-5.25 kcal/mol).ConclusionsThe coupling of amines and dansyl chloride enabled efficient, straightforward sulfonamide synthesis. The strategic design of sulfonamides with specific substituents endows diverse biological properties, including potential anti-cancer activity. The elucidation of the synthesized compounds with NMR and mass spectra confirmed their structures. Molecular docking analysis demonstrated that the synthesized sulfonamides exhibited favorable binding affinities toward the potential drug target 1AZM. Notably, all derivatives displayed higher binding affinities, ranging from -6.8 to -8.2 kcal/mol, than the recommended drug acetazolamide (-5.25 kcal/mol), thus suggesting their potential as highly effective analogues for further validation in cancer therapy.

Dataset Information

Case-crossover studies of therapeutics: design approaches to addressing time-varying prognosis in elderly populations.

Publications

Case-crossover studies of therapeutics: design approaches to addressing time-varying prognosis in elderly populations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets