The methods for handling missing data in clinical trials influence sample size requirements.
OBJECTIVE
Results of studies estimating osteoarthritis progression may be affected by missing values. In clinical trials assessing disease-modifying osteoarthritis drugs, sample sizes should be calculated using close estimates of outcome variables.


METHODS
Supposing a two-parallel group design in hip osteoarthritis clinical trials, we estimated sample sizes using the joint space width (JSW), number of patients with JSW progression >0.5 mm (JSN), time to total hip arthroplasty (THA), and time to JSN or THA using several approaches to deal with missing data.


RESULTS
Three-year clinical trials testing a treatment effect of 50%, with a power of 80%, could require sample sizes of 121 patients for JSW, 57 for JS progression using multiple imputation for handling missing values; 200 for THA; and 47 for JSN or THA. These numbers vary greatly depending on the approach chosen for handling missing data.


CONCLUSIONS
These results can help investigators plan clinical trials to select the primary outcome and a priori specify the way missing data will be handled.
Auleley
Guy-Robert
GR
Université Paris V-René Descartes, Faculté de Médecine Cochin Port-Royal and Clinique de Rhumatologie, Hôpital Cochin, AP-HP, Paris, France.
Giraudeau
Bruno
B
Baron
Gabriel
G
Maillefert
Jean-Francis
JF
Dougados
Maxime
M
Ravaud
Philippe
P
D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods; D015207:Osteoarthritis, Hip / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome
D018501:Antirheumatic Agents