Neuroscience. Kristiansand

Transkript

1 Neuroscience Kristiansand

2 Neuroscience Frank E. Sørgaard Medisinsk rådgiver «Hvordan kan MS medikamentenes effekt og sikkerhet sammenlignes»?

3 Neuroscience Når det ikke finne head to head studier Hva da? Gjøre en head-head studie Indirekte sammenligning av studier Databaser - Real World Evidence

4 Neuroscience Når det ikke finne head to head studier Hva da? Gjøre en head-head studie Indirekte sammenligning av studier Databaser - Real World Evidence

5 Sammenligninger av studier Kan man sammenligne to forskjellige studier gjort på to forskjellige populasjoner, ved to forskjellige tidspunkter og med to forskjellige medikamenter? Business or Operating Unit/Franchise or Department

6 Sammenligninger av studier Kan man sammenligne to forskjellige studier gjort på to forskjellige populasjoner, ved to forskjellige tidspunkter og med to forskjellige medikamenter? Business or Operating Unit/Franchise or Department

7 ...and what do we need to consider? Naive indirect comparison Comparison of the results of individual arms from different trials as if they were from the same trial Adjusted indirect comparison Comparison of different treatments adjusted according to covariates or to the results of their direct comparison with a common control (e.g. Bucher method a and network meta-analyses) Business or Operating Unit/Franchise or Department Bucher HC, Guyatt GH, Griffith LE, Walter SD: The results of direct and indirect treatment comparisons in metaanalysis of randomized controlled trials. J Clin Epidemiol Jun;50(6):

8 Naiv (enkel) sammenligning Placebo ARR 2 år Aktiv behandling ARR 2 år RRR Affirm Tysabri 1 Freedoms Gilenya 2 0,73 0,23 0,40 0,16 45 % 68,5 % 55 % 1: Polman CH, O'Connor PW, Havrdova E, et al. A randomized placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354: Business 2: Kappos L, or Radue Operating EW, O'Connor Unit/Franchise Pet al: A placebo-controlled or Departmenttrial of oral fingolimod in relapsing multiple sclerosis.n Engl J Med Feb 4;362(5):

9 Placebo relapse rate in different studies between 1993 and Business or Operating Unit/Franchise or Department

10 Relative risk of freedom from disease activity vs placebo The similarity assumption...can be violated if efficacy depends on patient characteristics Figure 1. Likelihood (relative risk) of freedom from disease activity for fingolimod 0.5 mg versus placebo by patient characteristics at baseline in pooled analyses of FREEDOMS and FREEDOMS II a 2,0 1,74 1,71 1,5 1,54 1,36 1,38 1,0 ITT population age <= 39 years age > 39 years Modified from: Nicolas et al: Relapse outcomes in patients with multiple sclerosis treated with fingolimod Business by previous injectable or Operating disease-modifying Unit/Franchise therapy and disease or duration. Department Poster: P3.248_AAN2015 Modified from: Derfuss et al: Relapse outcomes in patients with multiple sclerosis treated with fingolimod: Subgroup analyses of three phase 3 fingolimod trials Poster: P7.217_AAN 2015 Treatment naive Treatment experienced

11 % of patients free from 3-month confirmed disability progression The similarity assumption...can be violated if endpoints are defined differently across trials FREEDOMS criteria a Relative risk: 1.12 DEFINE/CONFIRM criteria b Relative risk: % 100% 80% 60% 40% 47% 42% 80% 60% 40% 75% 62% 20% 20% 0% Fingolimod 0.5 mg Placebo 0% Fingolimod 0.5 mg Placebo a) In FREEDOMS confirmed disability progression was considered to be an increase of 1 EDSS point for patients with a baseline score of 0 5.0, and of 0.5 points for patients with a baseline EDSS score of 5.5 b) In DEFINE and CONFIRM, disability progression was defined as an increase of 1 point in patients with an EDSS score of , and of at least 1.5 EDSS points in patients with a baseline EDSS score of 0 c) Data modified Business from Bergvall or Operating et al.: Consequences Unit/Franchise of different definitions or Department of confirmed disability progression across randomized trials of multiple sclerosis therapies Poster presented at ECTRIMS 2012, P1020

12 Indirect comparison model results: predicted efficacy for reducing relapse rates Final model Business covariates: age, or Operating previous DMT Unit/Franchise use, number of or Gd-enhancing DepartmentT1 lesions. Modified from: Nixon et al: Indirect comparisons of oral fingolimod versus natalizumab and cladribine for the treatment of relapsing remitting multiple sclerosis ARR, annualized relapse rate; CI, confidence interval; DMT, disease-modifying therapy; Gd, gadolinium. based on data from FREEDOMS, AFFIRM and CLARITY Poster ENS 2012 P344

13 Nettverkanalyser Business or Operating Unit/Franchise or Department

14 Så...Kan man... Business or Operating Unit/Franchise or Department