An approach to combining parallel and cross-over trials with and without run-in periods using individual patient data.
BACKGROUND
In active run-in trials, where patients may be excluded after a run-in period based on their response to the treatment, it is implicitly assumed that patients have individual treatment effects. If individual patient data are available, active run-in trials can be modelled using patient-specific random effects. With more than one trial on the same medication available, one can obtain a more precise overall treatment effect estimate.


METHODS
We present a model for joint analysis of a two-sequence, four-period cross-over trial (AABB/BBAA) and a three-sequence, two-period active run-in trial (AB/AA/A), where the aim is to investigate the effect of a new treatment for patients with pain due to osteoarthritis.


RESULTS
Our approach enables us to separately estimate the direct treatment effect for all patients, for the patients excluded after the active run-in trial prior to randomisation, and for the patients who completed the active run-in trial. A similar model approach can be used to analyse other types of run-in trials, but this depends on the data and type of other trials available.


CONCLUSIONS
We assume equality of the various carry-over effects over time.


CONCLUSIONS
The proposed approach is flexible and can be modified to handle other designs. Our results should be encouraging for those responsible for planning cost-efficient clinical development programmes.
Norwegian Computing Center - SAMBA, Oslo, Norway. Ingunn.Fride.Tvete@nr.no
Ingunn F
IF
Tvete
Inge C
IC
Olsen
Morten W
MW
Fagerland
Nils
N
Meland
Magne
M
Aldrin
Knut T
KT
Smerud
Lars
L
Holden
D015982:Bias; D018592:Cross-Over Studies; D006801:Humans; D015233:Models, Statistical; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology; D017063:Outcome Assessment, Health Care / Q000379:methods*; D059408:Pain Management / Q000379:methods; D016032:Randomized Controlled Trials as Topic