Browsing by Subject "comparative effectiveness"

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    Long-term Comparative Effectiveness of Rheumatoid Arthritis Treatment Strategies
    (2013-08) Jalal, Hawre
    Rheumatoid arthritis (RA) is a chronic debilitating disease characterized by progressive joint damage, reduced quality of life, loss of productivity and premature death. It affects 1% of the adult US population, and is one of the most demanding diseases on our healthcare resources. Biologic disease modifiers are new drugs that provide hope to improve the course of RA; however, biologics are among the most expensive specialty drugs. Although the treatment costs of RA have recently increased with the introduction of biologics, most of the economic and societal impacts are due to consequences of RA rather than direct treatment costs. Thus, the cost-effectiveness of biologics in RA is of high priority as recognized by many agencies including the National Institute of Health. This thesis focuses on three limitations of the current cost-effectiveness analyses (CEA) of biologics in RA. First, Most CEAs are based on randomized clinical trials (RCT) that are rarely applicable to real-life clinical practice. This thesis examines the long-term comparative clinical- and cost-effectiveness of biologics using clinical practice data from a large registry of RA patients (The National Data-Bank of Rheumatic Diseases). Second, we lack a meta-analytical approach specific to CEAs, and previous tools are deemed inappropriate. This thesis presents a novel approach of meta-analysis specific to CEAs. Using this tool we examine if prior CEAs of biologics in RA are consistent. Third, due to the biologics' high costs, RA treatment guidelines often recommend biologics as second line agents after nonbiologics. However, early aggressive treatment is crucial to avoid permanent joint damage. In this thesis we use Markov decision processes (MDP) as an innovative approach to identify the optimal timing of biologics in RA. The results from this analysis have significant policy, clinical and methodological implications. This work provides important insights into the comparative effectiveness of biologics in RA from a US societal perspective, which can influence health policy and medical insurance coverage decisions. Methodologically, the proposed meta-analytical approach can be applied to other conditions, and have the potential to reconcile the inconsistencies in published CEAs and improve the quality of future studies.
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    A modeling-based evaluation of the evidential basis for and cost effectiveness of intensive post-diagnosis extra-colonic surveillance of non-metastatic colorectal cancer patients
    (2018-03) Popp, Jonah
    Between 70-80% of colorectal cancer (CRC) patients present with non-metastatic disease and can potentially be cured with surgical resection. However, between 5-60% of these patients will suffer a recurrence, generally in the form of late-occurring metastatic disease. For this reason, most professional-society guidelines recommend intensive extra-colonic-focused surveillance (CT scans and routine testing for tumor-markers) of these patients for 3-5 years post-diagnosis with the aim of detecting recurrence at an earlier stage when it is more likely to be amenable to salvage surgery with a curative intent. Until recently, this practice was corroborated by the results of meta-analyses of randomized control trials (RCTs) comparing more intensive with less intensive (or no) surveillance. However, the negative results of two large recently-published RCTs – the UK FACS trial and the Italian GILDA trial - and of subsequently updated meta-analyses have cast doubt on the value of aggressive follow-up and ultimately the value of aggressive treatment of recurrent CRC. In this dissertation I use a modeling analysis to argue that the results of these two trials have been misinterpreted. Accordingly, the conclusions of the most recent meta-analyses are misguided and calls to throw in the towel on intensive follow-up are premature. The negative trial results are not surprising given the low recurrence rates of contemporary practice and thus the small proportion of patients who could potentially benefit from aggressive follow-up. I show that, if aggressive follow-up were to confer a survival advantage in virtue of increasing the chances of salvage therapy with a curative intent, the average benefit would be very small. Moreover, the two trials would have had essentially no chance to detect an effect of that size, and this problem of insufficient power was likely exacerbated in at least one of the trials by a sizable chance recurrence imbalance. I further show that it is unlikely that a RCT with adequate power could ever or will ever be possible. However, I argue there is reason to take seriously the hypothesis that aggressive use of follow-up testing and subsequent salvage therapy can offer a small survival advantage on average. Finally, I report the results of a modeling-based cost-effectiveness analysis to identify follow-up strategies that would be cost-effective if this hypothesis is correct.