Exponential decay for binary time-varying covariates in Cox models

2017 ◽  
Vol 37 (5) ◽  
pp. 776-788
Author(s):  
Charles Donald George Keown-Stoneman ◽  
Julie Horrocks ◽  
Gerarda Darlington
Keyword(s):  
Exponential Decay ◽  
Time Varying ◽  
Cox Models ◽  
Time Varying Covariates

Association of changes in circulating cell-free plasma DNA (cfDNA) and circulating tumor cells (CTC) during treatment with clinical outcome from olaparib in castration-resistant prostate cancer (CRPC): Exploratory analyses from the TOPARP-A trial.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 141-141 ◽  
Author(s):  
Joaquin Mateo ◽  
Helen Mossop ◽  
Jane Goodall ◽  
David Lorente ◽  
Nuria Porta ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
P Value ◽  
Time Varying ◽  
Castration Resistant Prostate Cancer ◽  
Plasma Dna ◽  
Cox Models ◽  
Castration Resistant ◽  
Treatment Switch ◽  
Response Biomarkers ◽  
Time Varying Covariates

141 Background: Response biomarkers are needed to optimize treatment switch decisions in CRPC patients. CTC and cfDNA may have clinical utility as response biomarkers; we studied them during olaparib treatment in a phase II trial in CRCP (Mateo et al NEJM 2015). Methods: CTC were enumerated using CellSearch (Jannsen Diagnostics) and cfDNA was extracted with the QIASymphony circulating DNA kit (Qiagen) from blood samples taken at baseline, 4- and 8-weeks (wk) of therapy. Radiological progression-free survival (rPFS) was defined as time from starting treatment to progression by RECIST 1.1, bone scan (PCWG2) or death. Overall survival (OS) was defined as time from starting treatment to death. CTC changes were categorized based on conversion from ≥ 5 to < 5 CTC/7.5ml blood and on ≥ 30% decline (Lorente et al Eur Urol 2016). cfDNA changes were evaluated as percentage change from baseline (continuous and binary). The prognostic value of CTC and cfDNA changes were assessed by Landmark analysis and Cox models with time-varying covariates; p-value < 0.01 were considered significant to account for multiple tests. Results: Overall, 13/47 (28%) and 16/42 (38%) evaluable patients had a CTC conversion at 4- and 8-wk respectively. A CTC conversion after 4-wk of olaparib associated with longer rPFS (median 8.9 vs 2.7 months [m], p = 0.001); a similar association was found at 8-wk. A 30% CTC decline at 4-wk also associated with longer rPFS (median 4.4 vs 2.6 m, p = 0.004). CTC conversion as a time-varying covariate associated with longer OS (HR 0.26, 95%CI 0.14-0.50, p < 0.001). Median baseline cfDNA was 31.6 ng/ml (IQR 19.4-57.1); 46 and 42 patients were evaluable for cfDNA changes at 4- and 8-wk. Percentage changes in cfDNA at 4- and 8- wk associated with rPFS (HR 1.01 and 1.005; p = 0.005 and 0.002 respectively) but association with OS was not significant. cfDNA declines ≥ 50% at 8- wk associated with longer rPFS (median 8.9 vs 2.7 m, p = 0.007) and OS (17.0 vs 10.1 m, p = 0.004). Conclusions: Decreases in CTC counts and cfDNA concentration associate with improved outcome from olaparib (rPFS, OS) in the TOPARP-A trial. Clinical trial information: NCT01682772.

scholarly journals Hydroxychloroquine and the risk of respiratory infections among RA patients

RMD Open ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. e001389
Author(s):  
Joel M Kremer ◽  
George Reed ◽  
Dimitrios A Pappas ◽  
LR Harold ◽  
Kevin Kane ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Smoking Status ◽  
Secondary Analysis ◽  
Time Varying ◽  
Biologic Dmards ◽  
Cox Models ◽  
Serious Infections ◽  
History Of ◽  
Upper Respiratory ◽  
Time Varying Covariates

ObjectivesTo determine the effect of hydroxychloroquine on the incidence of new respiratory infections in a large registry of rheumatoid arthritis (RA) patients compared with a matched cohort receiving other conventional disease-modifying antirheumatic drugs (csDMARDs).MethodsWe reviewed physician-reported infections including upper respiratory infections (URI), bronchitis and pneumonia in the Corrona RA registry from June 2008 to February 2020 with the goal of comparing infections in biologic/targeted synthetic (b/ts) DMARDs naive HCQ starts compared with starts of other csDMARDs and no HCQ. Patients on different interventions were compared using time-varying adjusted Cox models adjusting for age, sex, duration of RA, BMI, disease activity, smoking status, concurrent medications, season of the year, year of onset and history of serious infections, diabetes or cardiovascular disease (CVD). A secondary analysis in a set of propensity-matched starts were also compared adjusting for time-varying covariates. The analysis was repeated including URI and bronchitis only and also for serious respiratory infections only.ResultsNo evidence of differences was found in the incidence of any respiratory infection (URI, bronchitis, pneumonia) in patients receiving HCQ compared with other csDMARDs: HR=0.87 (0.70 to1.07) in adjusted analyses and HR=0.90 (0.70 to 1.17) in adjusted matched analysis. Similar results were found in the analysis of URI and bronchitis only and for serious respiratory infections only.ConclusionsIn patients with RA, the risk for respiratory infections was similar among patients using HCQ as compared to other non-biologic DMARDs.

scholarly journals A competing risks model with binary time varying covariates for estimation of breast cancer risks in BRCA1 families

2021 ◽  
pp. 096228022110089
Author(s):  
Yun-Hee Choi ◽  
Hae Jung ◽  
Saundra Buys ◽  
Mary Daly ◽  
Esther M John ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Competing Risks ◽  
Brca1 Mutation ◽  
Prophylactic Surgery ◽  
Time Varying ◽  
Cancer Risks ◽  
Competing Risks Model ◽  
Time Varying Covariates ◽  
Risk Reducing

Mammographic screening and prophylactic surgery such as risk-reducing salpingo oophorectomy can potentially reduce breast cancer risks among mutation carriers of BRCA families. The evaluation of these interventions is usually complicated by the fact that their effects on breast cancer may change over time and by the presence of competing risks. We introduce a correlated competing risks model to model breast and ovarian cancer risks within BRCA1 families that accounts for time-varying covariates. Different parametric forms for the effects of time-varying covariates are proposed for more flexibility and a correlated gamma frailty model is specified to account for the correlated competing events.We also introduce a new ascertainment correction approach that accounts for the selection of families through probands affected with either breast or ovarian cancer, or unaffected. Our simulation studies demonstrate the good performances of our proposed approach in terms of bias and precision of the estimators of model parameters and cause-specific penetrances over different levels of familial correlations. We applied our new approach to 498 BRCA1 mutation carrier families recruited through the Breast Cancer Family Registry. Our results demonstrate the importance of the functional form of the time-varying covariate effect when assessing the role of risk-reducing salpingo oophorectomy on breast cancer. In particular, under the best fitting time-varying covariate model, the overall effect of risk-reducing salpingo oophorectomy on breast cancer risk was statistically significant in women with BRCA1 mutation.

Does biologic therapy impact the development of PsA among patients with psoriasis?

2021 ◽  
Vol 81 (1) ◽  
pp. 80-86
Author(s):  
Elana Meer ◽  
Joseph F Merola ◽  
Robert Fitzsimmons ◽  
Thorvardur Jon Love ◽  
Shiyu Wang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Propensity Score ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Oral Therapy ◽  
Biologic Therapy ◽  
Therapy Group ◽  
Time Varying ◽  
Confounding By Indication ◽  
Cox Models

ObjectiveTo examine the association of biologic therapy use for psoriasis with incident psoriatic arthritis (PsA) diagnosis.MethodsA retrospective cohort study was conducted in the OptumInsights Electronic Health Record Database between 2006 and 2017 among patients with psoriasis between the ages of 16 and 90 initiating a therapy for psoriasis (oral, biologic or phototherapy). The incidence of PsA was calculated within each therapy group. Multivariable Cox models were used to calculate the HR for biologic versus oral or phototherapy using biologics as a time-varying exposure and next in a propensity score-matched cohort.ResultsAmong 1 93 709 patients with psoriasis without PsA, 14 569 biologic and 20 321 cumulative oral therapy and phototherapy initiations were identified. Mean age was lower among biologic initiators compared with oral/phototherapy initiators (45.9 vs 49.8). The incidence of PsA regardless of therapy exposure was 9.75 per 1000 person-years compared with 77.26 among biologic users, 61.99 among oral therapy users, 26.11 among phototherapy users and 5.85 among those without a prescription for one of the target therapies. Using a multivariable adjustment approach with time-varying exposure, adjusted HR (95% CI) for biologic users was 4.48 (4.23 to 4.75) compared with oral or phototherapy users. After propensity score matching, the HR (95% CI) was 2.14 (2.00 to 2.28).ConclusionsIn this retrospective cohort study, biologic use was associated with the development of PsA among patients with psoriasis. This may be related to confounding by indication and protopathic bias. Prospective studies are needed to address this important question.

The third birth in Great Britain

1988 ◽  
Vol 20 (4) ◽  
pp. 489-496 ◽  
Author(s):  
Robert E. Wright ◽  
John F. Ermisch ◽  
P. R. Andrew Hinde ◽  
Heather E. Joshi
Keyword(s):  
Labour Force ◽  
Strong Association ◽  
Labour Force Participation ◽  
Age At First Birth ◽  
Time Varying ◽  
Female Labour ◽  
Subsequent Fertility ◽  
Lower Fertility ◽  
Time Varying Covariates ◽  
The Relationship

SummaryThe relationship between female labour force participation, and other socioeconomic factors, and the probability of having a third birth is examined, using British data collected in the 1980 Women and Employment Survey, by hazard regression modelling with time-varying covariates. The results demonstrate the strong association between demographic factors, e.g. age at first birth and birth interval and subsequent fertility behaviour. Education appears to have little effect. Surprisingly, women who have spent a higher proportion of time as housewives have a lower risk of having a third birth. This finding is in sharp disagreement with the conventional expectation that cumulative labour force participation supports lower fertility. These findings are briefly compared with similar research carried out in Sweden.

scholarly journals A General and Robust Estimation Method for the Case-Time-Control Design

2019 ◽  
Vol 49 (1) ◽  
pp. 349-365
Author(s):  
Arvid Sjölander ◽  
Yang Ning
Keyword(s):  
Robust Estimation ◽  
Arbitrary Number ◽  
Estimation Method ◽  
Control Design ◽  
Time Varying ◽  
Time Control ◽  
Measured Time ◽  
Important Extension ◽  
Time Varying Covariates

The case-time-control design is a tool to control for measured, time-varying covariates that increase montonically in time within each subject while also controlling for all unmeasured covariates that are constant within each subject across time. Until recently, the design was restricted to data with only two timepoints and a single binary covariate, or data with a binary exposure. Sjölander (2017) made an important extension that allows for an arbitrary number of timepoints and covariates and a nonbinary exposure. However, his estimation method requires fairly strong model assumptions, and it may create bias if these assumptions are violated. We propose a novel estimation method for the case-time-control design, which to a large extent relaxes the model assumptions in Sjölander. We show in simulations that this estimation method performs well under a range of scenarios and gives consistent estimates when Sjölander’s estimation does not.

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