RESEARCH - A new design for registration trials in RA allowing secondary head-to-head comparisons with standard of care treatment

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Ann Rheum Dis. 2010 Jan;69(1):4-6.

A new design for registration trials in rheumatoid arthritis allowing

secondary head-to-head comparisons with standard of care treatment

including biologicals.

Boers M.

Department of Epidemiology and Biostatistics, VU University Medical

Center, PK 6Z 165, PO Box 7057, 1007 MB Amsterdam, The Netherlands.

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.

PMID: 20007620

http://www.ncbi.nlm.nih.gov/pubmed/20007620

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