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Placebo Effect in Chronic Inflammatory Demyelinating Polyneuropathy: The PATH study and a systematic review
Lewis RA, Cornblath DR, Hartung HP, Sobue G, Lawo JP, Mielke O, Durn BL, Bril V, Merkies ISJ, Bassett P, et al
J Peripher Nerv Syst. 2020
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Abstract
Background and Aims The PATH study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on immunoglobulin G (IgG) and then be restabilized on IgG before being randomized to placebo or one of two doses of subcutaneous immunoglobulin (SCIG). Nineteen of the 51 subjects (37%) randomized to placebo did not relapse over the next 24 weeks. This article explores the reasons for this effect. A post-hoc analysis of the PATH placebo group was undertaken. A literature search identified other placebo controlled CIDP trials for review and comparison. In PATH, subjects randomized to placebo who did not relapse were significantly older, had more severe disease, and took longer to deteriorate in the IgG dependency period compared with those who relapsed. Published trials in CIDP, whose primary endpoint was stability or deterioration, had a mean non-deterioration (placebo effect) of 43%, while trials with a primary endpoint of improvement had a placebo response of only 11%. Interpretation Placebo is an important variable in the design of CIDP trials. Trials designed to show clinical improvement will have a significantly lower effect of this phenomenon than those designed to show stability or deterioration. This article is protected by copyright. All rights reserved.
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Systematic review and analysis of efficacy of recombinant factor IX products for prophylactic treatment of hemophilia B in comparison with rIX-FP
Davis J, Yan S, Matsushita T, Alberio L, Bassett P, Santagostino E
Journal of medical economics. 2019;:1
Abstract
AIMS: Prophylaxis with standard-acting recombinant factor IX (rFIX) in hemophilia B patients requires frequent injections. Extended half-life (EHL) products allow for prolonged dosing intervals and so reduce this treatment burden. Three technologies are employed to extend the half-life of FIX; glycopegylation, Fc-fusion, and albumin fusion. rIX-FP is a novel albumin fusion protein, which allows for a prolonged dosing interval of up to 14 days. A systematic review and indirect statistical comparison was performed to evaluate the efficacy of both EHL and standard-acting rFIX products compared with rIX-FP in Phase III trials for prophylaxis in adult hemophilia B patients. MATERIALS AND METHODS A systematic search was conducted in both EMBASE and PubMed to identify Phase III trials of prophylactic rFIX treatment in previously treated, hemophilia B patients aged ≥12 years (FIX: ≤2%). Annualized bleeding rate (ABR), spontaneous ABR (AsBR), and joint ABR (AjBR) data were extracted from each study. A z-test was performed using the mean of each parameter, and the mean difference in outcome between studies was calculated. RESULTS Seven articles investigating six rFIX products were identified. Median ABR, AsBR and AjBR ranged from 0-3.0, 0-1.0, and 0-1.1 (means 0.8-4.26, 0.13-2.6, and 0.34-2.85), respectively. rIX-FP achieved lowest median and mean values in all three parameters. Z-tests showed that mean ABR was significantly lower for rIX-FP 7-day prophylaxis compared with the majority of standard-acting and other EHL rFIX products. LIMITATIONS The low number of appropriate trials available for comparison limits the quantity of data available for comparison and restricts the use of methods of adjustment for variance in study design or patient characteristics. However, these limitations are shared with similar analyses published in this field. CONCLUSION This indirect comparison of Phase III trials indicates that rIX-FP efficacy compares favorably versus other rFIX products for prophylaxis in hemophilia B.
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Crystalloids vs. colloids for fluid resuscitation in the Intensive Care Unit: A systematic review and meta-analysis
Martin GS, Bassett P
Journal of critical care. 2018;50:144-154
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Abstract
PURPOSE Guidelines recommend crystalloids for fluid resuscitation in sepsis/shock and switching to albumin in cases where crystalloids are insufficient. We evaluated hemodynamic response to crystalloids/colloids in critically ill adults. MATERIALS AND METHODS The primary research question was: "Are crystalloids sufficient for volume replacement in severe indications (intensive care unit [ICU]/critical illness)?" Randomized, controlled trials (RCTs) were identified using PubMed and EMBASE, and screened against predefined inclusion/exclusion criteria. Meta-analyses were performed on extracted data. RESULTS Fifty-five RCTs (N=27,036 patients) were eligible. Central venous pressure was significantly lower with crystalloids than with albumin, hydroxyethyl starch (HES), or gelatin (all p<.001). Mean arterial pressure was significantly lower with crystalloids vs. albumin (mean difference [MD]: -3.5mmHg; p=.03) or gelatin (MD: -9.2mmHg; p=.02). Significantly higher volumes of crystalloids were administered vs. HES (MD: +1775mL); volume administered was numerically higher vs. albumin (MD: +1985mL). Compared with the albumin group, cardiac index was significantly lower in the crystalloid group (MD: -0.6L/min/m(2), p<.001). All mortality and 90-day mortality were significantly lower for crystalloids compared with HES (relative risk 0.91; p=.009 and 0.9; p=.005, respectively). CONCLUSIONS Crystalloids were less efficient than colloids at stabilizing resuscitation endpoints; guidance on when to switch is urgently required.