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    Genebank identifiers of the nucleotide sequences of atpA, pheS and rpoA genes, used for the phylogenetic analyses. Table S2. NCBI Refseq/Genbank assembly accession numbers for the comparative genomic analysis of Leuconostoc species (29.09.2015). Table S3. L. gelidum subsp. gasicomitatum draft genomes statistics. Figure S1. Phylogenetic tree showing the relationship of L. citreum 1300_LCIT, L. gelidum subsp. gasicomitatum 1301_LGAS and L. inhae LMG 22919 genomes to other Leuconostoc species. (PDF 406 kb

    The estimated survival function and conditional probability of dying each month (i.e., the monthly hazard) for NHT (––) and SoC (-—-) patients up to 82 months after a potential drug prescription of NHT.

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    The estimated survival function and conditional probability of dying each month (i.e., the monthly hazard) for NHT (––) and SoC (-—-) patients up to 82 months after a potential drug prescription of NHT.</p

    The effect on mortality of NHT against SoC.

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    Estimates, 95% Bonferroni confidence intervals, and overall mortality in each month (x).</p

    Distribution of time between diagnosis and NHT prescription.

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    Distribution of time between diagnosis and NHT prescription.</p

    Results from the sensitivity analyses.

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    BackgroundThis paper presents results from one of the few comparative effectiveness evaluations of novel antiandrogen medications (NHT) against standard of care (SoC) for patients suffering from metastatic castrate-resistant prostate cancer (mCRPC).MethodsThe design and the analysis are published in a protocol before accessing outcome data. Two groups of patients are balanced on hundreds of important covariates measured before the prostate cancer diagnosis and up to the date of the prescription. While the design yields balance on the observed covariates, one cannot discard the possibility that unobserved confounders are not balanced. The unconfoundedness assumption is assessed by estimating placebo regressions on two health measures, not included in the design but added together with the outcome data after protocol publication.ResultsWe find a substantial (64 percent) increase in mortality for patients prescribed with NHT rather than SoC. However, based on the results from one of the two placebo regressions, we cannot rule out that the difference in mortality may be due to confounding. Using a bounding strategy of the effect, we can, however, rule out that NHT reduces mortality compared to SoC. Under an empirical valid assumption that most mCRPC patients who die suffer from bone metastases, we have a strong indication of increased skeleton-related events in patients if prescribed NHT against SoC.ConclusionsGenerally, the SoC for this group of patients is docetaxel. Given the substantially higher costs of many of the NHT, the finding of no positive effects from NHT on both mortality and SRE is important. More comparative studies, including studies analysing quality of life outcomes, are thus needed.</div

    Summary statistics.

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    BackgroundThis paper presents results from one of the few comparative effectiveness evaluations of novel antiandrogen medications (NHT) against standard of care (SoC) for patients suffering from metastatic castrate-resistant prostate cancer (mCRPC).MethodsThe design and the analysis are published in a protocol before accessing outcome data. Two groups of patients are balanced on hundreds of important covariates measured before the prostate cancer diagnosis and up to the date of the prescription. While the design yields balance on the observed covariates, one cannot discard the possibility that unobserved confounders are not balanced. The unconfoundedness assumption is assessed by estimating placebo regressions on two health measures, not included in the design but added together with the outcome data after protocol publication.ResultsWe find a substantial (64 percent) increase in mortality for patients prescribed with NHT rather than SoC. However, based on the results from one of the two placebo regressions, we cannot rule out that the difference in mortality may be due to confounding. Using a bounding strategy of the effect, we can, however, rule out that NHT reduces mortality compared to SoC. Under an empirical valid assumption that most mCRPC patients who die suffer from bone metastases, we have a strong indication of increased skeleton-related events in patients if prescribed NHT against SoC.ConclusionsGenerally, the SoC for this group of patients is docetaxel. Given the substantially higher costs of many of the NHT, the finding of no positive effects from NHT on both mortality and SRE is important. More comparative studies, including studies analysing quality of life outcomes, are thus needed.</div

    Analysis of missing in the proxy variables.

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    BackgroundThis paper presents results from one of the few comparative effectiveness evaluations of novel antiandrogen medications (NHT) against standard of care (SoC) for patients suffering from metastatic castrate-resistant prostate cancer (mCRPC).MethodsThe design and the analysis are published in a protocol before accessing outcome data. Two groups of patients are balanced on hundreds of important covariates measured before the prostate cancer diagnosis and up to the date of the prescription. While the design yields balance on the observed covariates, one cannot discard the possibility that unobserved confounders are not balanced. The unconfoundedness assumption is assessed by estimating placebo regressions on two health measures, not included in the design but added together with the outcome data after protocol publication.ResultsWe find a substantial (64 percent) increase in mortality for patients prescribed with NHT rather than SoC. However, based on the results from one of the two placebo regressions, we cannot rule out that the difference in mortality may be due to confounding. Using a bounding strategy of the effect, we can, however, rule out that NHT reduces mortality compared to SoC. Under an empirical valid assumption that most mCRPC patients who die suffer from bone metastases, we have a strong indication of increased skeleton-related events in patients if prescribed NHT against SoC.ConclusionsGenerally, the SoC for this group of patients is docetaxel. Given the substantially higher costs of many of the NHT, the finding of no positive effects from NHT on both mortality and SRE is important. More comparative studies, including studies analysing quality of life outcomes, are thus needed.</div

    Effects on PAIN of NHT against SoC.

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    Estimates and 95% Bonferroni corrected confidence intervals. We let all patients who die either have no morbidity outcome or a morbidity outcome (i.e. PAIN = 0 or PAIN = 1). Since the mortality with the NHT is observed to be higher than without a SoC the first case (i.e. PAIN = 0) provides a lower bound estimate of the effectiveness of the NHT while the second one provides an upper bound on PAIN. Lower (left panel) and upper (right panel) bounds of potential effect. (TIF)</p

    The effects on mortality of NHT against SoC.

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    Estimates, 95% Bonferoni corrected confidence intervals and overall level of mortality for each month. Early (left panel) and late (right panel) prescriptions. (TIF)</p

    The effect on PAIN of NHT against SoC.

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    Estimates, 95% Bonferroni confidence intervals and overall mortality for each month. Updated entropy weights. (TIF)</p
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