The WMW test, stratified by the presence or absence of diabetes mellitus at baseline was applied separately to three comparisons between each treatment group and the placebo group to compare the primary efficacy endpoint [9]. In Study no. The efficacy and safety endpoints analyses were performed as planned in the CT protocol. 2. In line. Explicit reporting on the blinding mechanism for patients and trial personnel was given only in one of the RCTs. The agency anticipates many more approvals in … However, the outcomes reported, including overall survival (OS) and the laboratory variables (complete blood count and chemistry panel), did not involve judgement that would potentially lead to bias. 2004–002508-13, mITT analyses were performed. 2006–001246-13 did not provide specific information on the masking of participants. By closing this message, you are consenting to our use of cookies. Latest report from The three-year follow-up of the Phase I/II clinical trial showed positive results, with the median number of annualized treated bleeding events at zero and a reduction of the median use of exogenous factor VIII from 138.5 infusions to 0 infusions per year, in 7 out of 15 participants. However, the primary efficacy parameter was assessed by PWT, which did not involve outcome assessor judgement. The risk of bias due to the choice of reported results for all RCTs was considered low. LOCF is commonly used as a method of imputing missing data in longitudinal studies. Although no COSs in respective therapeutic areas were available during the RCTs design, the most common clinical field outcome measures were planned and performed. 2004–002508-13, out of 289 randomised participants across the 4 patient groups, 273 patients (94.5%) that had at least one treadmill test were included in the efficacy analysis (mITT). To learn about our use of cookies and how you can manage your cookie settings, please see our Cookie Policy. GlobalData’s primary research revealed that patients with severe forms of the disease are increasingly treated on a prophylactic basis rather than on-demand after bleeds, since this significantly reduces the occurrence of bleeding episodes. In study no. 3099067 These sets serve to advise on a number of essential outcomes that should be measured and reported in all clinical trials for a specific condition [15]. After the first interim assessment of unblinded patient safety data, assessment by the independent Data Monitoring Committee (DMC) was blinded [9]. In three CTs, the risk in all bias domains was rated as low and only one CT identified a moderate risk of bias due to lack of information regarding the randomization process. These two clotting factors have different half-life durations in the blood. We use cookies to improve your website experience. Clinical examination results, including pulmonary function, gas transfer markers, and systemic inflammation indicators were examined in a masked manner by the DMEC [14]. The principles of the CONSORT statement should be widely followed for improving the quality of reporting of RCTs. In addition, only limited data were provided in the reviewed RCTs regarding deviations from intended intervention that were inconsistent with the trial protocol. The CT data were analysed using the predetermined methods of analysis. There was no consensus reached on optimal phase II endpoints in acute or chronic heart failure trials [16] and study no. In this domain, RCTs were reviewed for risk of bias that arose because of selection of the reported results [4]. This data is important for assessing the risk of bias in outcome measurement, especially when knowledge of the intervention can influence the judgment of the outcome assessor. This significantly limits the conclusions that can be drawn about the methodology and design of CTs with GTMPs due to the small number of identified RCTs. There was no specific data provided on trial participants masking. No deviations were observed between planned and published outcome measurements and analyses. Missing data from the 26-week peak walking time test (PWT), where the percentage change from baseline was used as primary efficacy endpoint, was input to the last-observation-carried-forward method (LOCF). Register to receive personalised research and resources by email, Gene therapy randomised clinical trials in Europe – a review paper of methodology and design, Faculty of Public Health, Medical University Sofia, Sofia , Bulgaria, Department of Health Technology Assessment, Faculty of Public Health, Medical University Sofia, Sofia , Bulgaria, Public Health Department, Aix-Marseille University , Marseille, France, Challenges with advanced therapy medicinal products and how to meet them, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement, RoB 2: a revised tool for assessing risk of bias in randomised trials, Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial, Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial, CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials, Ad2/HIF-1α/VP16, Abbreviated Clinical Study Report: PADHIF00704, Effect of hypoxia-inducible factor-1α gene therapy on walking performance in patients with intermittent claudication, Vaccination of metastatic renal cancer patients with MVA-5T4: a randomized, double-blind, placebo-controlled phase III study, Design of a phase 2b trial of intracoronary administration of AAV1/SERCA2a in patients with advanced heart failure: the CUPID 2 trial (calcium up-regulation by percutaneous administration of gene therapy in cardiac disease phase 2b), Allowing for uncertainty due to missing and LOCF imputed outcomes in meta-analysis, A randomised, double-blind, placebo-controlled trial of repeated nebulisation of non-viral cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy in patients with cystic fibrosis, Standardising outcomes for clinical trials and systematic reviews, Clinical outcome endpoints in heart failure trials: a European society of cardiology heart failure association consensus document, Indicators of outcome quality in peripheral arterial disease revascularizations – a Delphi expert consensus, Progress in cystic fibrosis and the CF therapeutics development network. (2020). In study no. Regulatory review of the first ever gene therapy for haemophilia to start in January 2020 GlobalData Healthcare 14 January 2020 (Last Updated January 14th, 2020 16:13) In study no. Such errors are less probable when outcome assessors are blinded to intervention assignment. In study no. These results were published in the New England Journal of Medicine in January 2020. Selection of reliable and well-defined objective endpoints which demonstrate clinical benefits and design plans for managing missing outcomes will minimize the bias in outcome analysis. Study nos. There were no observed inconsistencies between outcome measures and analyses intentions and publications in the reviewed RCTs. 5 Howick Place | London | SW1P 1WG. US KOLs interviewed by GlobalData consider the time to market a deciding factor for the success of a product and agree that a first-in-market drug can achieve higher market shares than its contenders. Given the great potential of gene therapy in the haemophilia market, more companies are developing gene therapies for both indications, A and B. Thus, there are few or no therapeutic alternatives for patients, not always established clinical pathways for development, and the limited number of patients does not generate the data required for treatment approval. 7. The relevant data were extracted once the database was locked and the researchers were unblinded [14]. So far, the FDA has approved just four gene therapy treatments but expects that it will be reviewing anywhere between 10 to 20 new candidates in this … 2004–002508-13, the methods of outcome measurement were very specific and the same measurement methods and thresholds in both the intervention and placebo groups were used at comparable time points. 2012–001700-37, 2011–004761-33 and 2006–001246-13, were assessed with low risk of bias in this domain. Pfizer and UniQure are testing their drugs, fidanacogene elaparvovec and AMT-061 respectively, in haemophilia B, while Spark is chasing after BioMarin in haemophilia A with its pipeline therapy SPK-8011. Browse over 50,000 other reports on our store. In November 2019, BioMarin, a biotechnology company specialising in developing therapies for rare diseases driven by genetic causes, submitted a marketing authorization application (MAA) to the European Medicines Association (EMA) for its investigational product valoctocogene roxaparvovec, a gene therapy targeted to patients with severe haemophilia A. Another limitation of this review is that only RCTs were considered for analysis. Gene Therapy Global Market Report 2020-30: COVID-19 Growth and Change provides the strategists, marketers and senior management with the critical information they need to assess the global gene therapy market market.New York, Nov. 24, 2020 (GLOBE NEWSWIRE) -- announces the release of the report "Gene Therapy Global Market Report 2020-30: Covid 19 Growth …

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