Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Efficacy Trial) was such an example [7], where at the second interim analysis thecumulative incidence of lung cancer was higher in the active treatment arm thanin the placebo group. This led to the DSMB and steering committee recognizingthe extremely limited prospect of a favorable overall effect.In addition, if serious adverse event rates are unacceptably higher in the newtreatment group than in the control group, the trial may be terminated orsuspended until protocol modifications can be instituted. A trial by the MedicalResearch Council Lung Cancer Working Party (MRC LU16) was stopped becausethe interim analysis showed that although the palliative effects of treatment weresimilar in the treatment groups, there was increased hematological toxicity andsignificantly worse survival in the study treatment (oral etoposide) group [8].Furthermore, the DSMB can also recommend extending (longer follow-up) orexpanding (increasing numbers of patients recruited) the trial if the projectionssuggest a more definitive result will only arise with this amendment. This mayoccur if the assumed event rates in the control group are not met; either due torecruitment of a low risk group, or because medical advances in such a patientgroup have improved morbidity beyond the expectations of such patients whenthe power calculations for the trial were originally performed, or if dropouts arehigher than expected. Finally, if similar large trials report conclusively then itmight be unnecessary and unethical to continue the current trial. The DSMB is,therefore, very critical to the success of a trial.ConclusionInterim monitoring is a critical part of clinical trials research. The benefits ofinterim monitoring and appropriate statistical analysis methods are to increasethe ethical, scientific, and economic value of clinical trials for patients,investigators, and sponsors alike. For this reason it is of key importance thatmembers of the DSMB be chosen wisely and have sufficient expertise, knowledge,and independence to be able to make tough decisions about trial progress.Further information on data monitoring and interim analysis can be found inreferences [9] and [10].References1. Title 21, Code of Federal Regulations, Part 312.32 (c).2. Jennison C, Turnbull BW. Group Sequential Methods with Applications to Clinical Trials.London: Chapman and Hall, 1999.361