A new design for registration trials in rheumatoid arthritis allowing secondary head-to-head comparisons with standard of care treatment including biologicals.

Abstract:

:Current drug development programs produce high quality data on the efficacy of new drugs, substantial data on safety, but little data on actual applicability of the new product compared to standard of care. After successful registration and launch, such data require years to accumulate and often remain incomplete. This viewpoint proposes a new trial design for phase 2 and 3 drug trials in rheumatoid arthritis. In this design the trial starts conventionally: patients that are inadequate responders to standard treatment (usually methotrexate) are randomised to receive the experimental drug or placebo on the background of continued (methotrexate) treatment. However, after 3 months all patients in the placebo group are additionally treated with one and the same standard of care treatment (usually an inhibitor of tumour necrosis factor) and all patients in the experimental group are additionally treated with a placebo corresponding to the chosen standard of care treatment. This design allows primary assessment of efficacy and safety of the experimental drug compared with placebo at the ethically acceptable limit of 3 months, followed by secondary assessments of efficacy (including durability) and safety compared to standard of care. The secondary assessments are observational and thus more prone to bias, but it is argued that the potential for bias is limited in this setting. Widespread adoption of the design will greatly help to determine the place of a new product in the spectrum of treatment possibilities of rheumatoid arthritis.

journal_name

Ann Rheum Dis

authors

Boers M

doi

10.1136/ard.2009.110007

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

4-6

issue

1

eissn

0003-4967

issn

1468-2060

pii

69/01/4

journal_volume

69

pub_type

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