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A standardization approach to compare treatment safety and effectiveness outcomes between clinical trials and real-world populations in psoriasis.

ABSTRACT: BACKGROUND:Patients recruited in randomized controlled trials (RCTs) for biologic therapies in psoriasis are not fully representative of the real-world psoriasis population. OBJECTIVES:Firstly, to investigate whether patient characteristics are associated with being included in a psoriasis RCT. Secondly, to estimate the differences in the incidence of severe adverse events (SAEs) and the response rate between RCT and real-world populations of patients on biologic therapies for psoriasis using a standardization method. METHODS:Data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) were appended to individual participant-level data from two RCTs assessing ustekinumab in patients with psoriasis. Baseline variables were assessed for association of being in an RCT using a multivariable logistic regression model. Propensity score weights were derived to reweigh the registry population so that variables had the distribution of the trial population. We measured the C-statistic of the model with trial status as the dependent variable, and the risk differences in the incidence rate of SAEs in the first year and Psoriasis Area and Severity Index (PASI) after 6 months in the BADBIR cohort before and after weighting. RESULTS:In total 6790 registry and 2021 RCT participants were included. The multivariable logistic regression model had a C-statistic of 0.82 [95% confidence interval (CI) 0.81-0.83]. The risk differences for the incidence rate of SAEs and the proportion of patients with PASI < 1.5 were 9.27 (95% CI -3.91-22.5) per 1000 person-years and 0.95 (95% CI -1.98-4.15), respectively. CONCLUSIONS:Our results suggest that RCTs of biologic therapies in patients with psoriasis are not fully representative of the real-world population, but this lack of external validity does not account for the efficacy-effectiveness gap. What's already known about this topic? Patients with psoriasis who would not be eligible for randomized controlled trials (RCTs) investigating biologic therapies have a greater risk of serious adverse events and lower treatment effectiveness than patients who would have been eligible. What does this study add? Baseline patient characteristics were shown to be predictive of whether a patient would have been eligible for enrolment in an RCT for psoriasis biologic therapy. We did not find any efficacy-effectiveness gap between the sample representative of the real-world population of patients with psoriasis and the sample representative of the RCT population. Factors outside of baseline patient characteristics, such as observer effect and higher adherence in RCTs, may be more influential in any efficacy-effectiveness gap between trial and real-world populations of patients with psoriasis.

SUBMITTER: Yiu ZZN

PROVIDER: S-EPMC6916305 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A standardization approach to compare treatment safety and effectiveness outcomes between clinical trials and real-world populations in psoriasis.

Yiu Z Z N ZZN Mason K J KJ Barker J N W N JNWN Hampton P J PJ McElhone K K Smith C H CH Warren R B RB Griffiths C E M CEM Lunt M M Burden A D AD

The British journal of dermatology 20190702 6

<h4>Background</h4>Patients recruited in randomized controlled trials (RCTs) for biologic therapies in psoriasis are not fully representative of the real-world psoriasis population.<h4>Objectives</h4>Firstly, to investigate whether patient characteristics are associated with being included in a psoriasis RCT. Secondly, to estimate the differences in the incidence of severe adverse events (SAEs) and the response rate between RCT and real-world populations of patients on biologic therapies for pso ...[more]

PMID: 30822358

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Project description:BackgroundLittle is known about the treatment outcomes of secukinumab in clinical practice, which differ from those in clinical trials. The effectiveness of biologics may differ in psoriasis patients with previous biologics exposure. The objective of this study was to investigate the real-world effectiveness and safety of secukinumab therapy and analyze subgroups stratified by reimbursement or prior biologic failure.MethodsThis retrospective multicenter study collected data from a cohort of 118 consecutive patients who received secukinumab treatment between December 2015 and March 2018. Effectiveness was evaluated by degree of improvement in the Psoriasis Area and Severity Index (PASI) scores. Adverse events and reasons for discontinuation were also recorded.ResultsThe mean PASI improvement rate at weeks 4, 12, 24, and 36 was 63.5%, 77.7%, 78.7%, and 76.0%, respectively. Compared with reimbursed patients, nonreimbursed patients had a significantly lower baseline PASI and a shorter mean disease duration of psoriasis; they were more frequently biologic-naïve, had used less prior traditional antipsoriatic drugs and were more likely to be treated with secukinumab 150 mg. The effectiveness of secukinumab in nonreimbursed patients was superior despite higher discontinuation rates. Compared with patients without prior biologic failure, patients with prior biologic failure had a significantly lower mean PASI improvement at weeks 12, 24, 36, and 48. The decline in response rates to secukinumab tended to be more pronounced for patients who failed ustekinumab than tumor necrosis factor-α inhibitors. Moreover, the number of prior biologic failures was associated with a decreased response rate and increased likelihood of secondary loss of effectiveness of secukinumab therapy.ConclusionIn a real-life clinical setting, the characteristics of nonreimbursed patients receiving secukinumab treatment differed from those of reimbursed patients. The PASI improvement for secukinumab was substantial but lower than that in clinical trials. The number and classes of prior biologic failures impact the treatment response to secukinumab.

Project description:BACKGROUND:The promise of real-world evidence (RWE) is especially relevant to pediatrics, where medicines prescribed for children are often used without evidence derived from randomized clinical trials. OBJECTIVES:The aim of this systematic review was to describe the state of RWE in pediatrics by identifying observational studies published during 2016 that used RWE to assess medication safety or effectiveness in children. METHODS:An electronic search of PubMed was combined with an extended search of references within systematic reviews and expert suggestions. Studies were included if they reported on an infant or child under 18 years with exposure to medications; assessed safety or effectiveness; specified a comparison or control group, and were published in English in 2016. Data extraction was conducted by one team member using a standardized form and reviewed by a second team member. Study quality was assessed using the GRACE checklist for rating the quality of observational studies. RESULTS:After removing duplicates, 915 citations were screened and 29 studies met the eligibility criteria. Most of the eligible studies relied on primary data collection or chart review at a single institution and did not use the growing number of administrative or electronic health record databases available. One-quarter of the studies did not use well-established statistical methods to control for confounders. No single disease group or medication predominated, and age groups ranged from infants to adolescents. CONCLUSIONS:A small body of observational studies published in 2016 were categorized by the study team as using real-world data to assess medication safety or effectiveness in children. Studies varied in age groups, diseases or conditions, and methods, and may not have fully met the FDA definition of RWE. Our review indicates that the use of RWE is not fully developed in pediatrics, and suggests an opportunity to further develop capabilities and more fully leverage administrative and electronic health record databases to study medication safety and effectiveness in children. Our systematic review appears generalizable to pediatrics broadly, and documents that the high level of activity in RWE in general has had less of an impact on pediatrics.

Project description:IntroductionMigraine shows a significantly higher prevalence in women, especially during reproductive age when menstrual-related hormonal fluctuations represent the most common migraine trigger. Indeed, over 50% of patients report a higher occurrence of migraine attacks during the perimenstrual window. Menstrual migraine attacks are consistently referred to as more disabling, less responsive to symptomatic treatments, longer in duration, and more prone to relapse than non-menstrual migraine attacks. Evidence strongly suggests that estrogen fluctuations are involved in migraine attacks worsening during the perimenstrual window through several mechanisms directly or indirectly involving the CGRP pathway. We aimed to evaluate whether mAbs blocking CGRP-ligand or receptor (CGRP-mAbs) could represent an effective and safe preventive treatment for menstrual migraine attacks in patients with menstrual-related migraine (MRM) with previous treatment failures.MethodsForty patients with MRM with at least three previous treatment failures received monthly CGRP-mAbs. At the baseline and after six CGRP-mAbs administrations, patients underwent to extensive interviews to assess frequency, duration, intensity, and responsiveness to painkiller intake of migraine attacks occurring during the perimenstrual window.ResultsAfter six administrations of CGRP-mAbs we observed a reduction of median menstrual migraine frequency (from 5 to 2 days per month), pain intensity (from 8/10 to 6/10), and attacks duration (from 24 to 8 h) (p < 0.001). Nevertheless, a significant increase in the percentage of responding to migraine painkillers was observed from 42.5% at baseline to 95% at T1 (p < 0.001).ConclusionsCGRP-mAbs could represent a safe and effective preventive therapeutic strategy able to reduce the disabling burden of menstrual migraine attack frequency, duration, intensity, and significantly improve the response to painkillers. These findings could be related to and further indirectly prove the greater influence of CGRP-mediated mechanisms in the pathophysiology of menstrual migraine attacks.

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A standardization approach to compare treatment safety and effectiveness outcomes between clinical trials and real-world populations in psoriasis.

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A standardization approach to compare treatment safety and effectiveness outcomes between clinical trials and real-world populations in psoriasis.

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