title: Clinical trials in cervical intraepithelial neoplasia: balancing the need for efficacy data with patient safety.
abstract: OBJECTIVE.: Trial designs for novel nonsurgical, nonablative therapies for cervical intraepithelial neoplasia grades 2 and 3 (CIN 2,3) must ensure patient safety while providing sufficient time to show clinical effects. We propose an observation period based on literature and current practice. MATERIALS AND METHODS.: We reviewed 3 types of literature regarding observation of untreated CIN 2,3: 1) the management of CIN in pregnancy, perhaps the best existing model of observation; 2) the natural history of untreated CIN 2,3; and 3) the optimal means of protecting patient safety during longer-term follow-up of untreated CIN 2,3 lesions. RESULTS.: Data from both the pregnant and nonpregnant patient populations indicate that delaying treatment of CIN for periods of several weeks to several months is rarely associated with clinically significant disease progression. Screening and follow-up criteria that promote patient safety have been suggested and seem adaptable to clinical trials. CONCLUSIONS.: Careful screening and follow-up of patients with CIN 2,3 allows an observation period of at least 6 months after nonsurgical, nonablative therapy in clinical trials.
authors.affiliation: 1BioStrategics Consulting Ltd, Marblehead, MA; 2ZYCOS Incorporated, Lexington, MA; 3Frauenklinik der Medizischen Hochschule, Hannover, Germany; and 4Keck/University of Southern California School of Medicine, Los Angeles, CA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Silverman
authors.forename: Mary Lynne
authors.initials: ML
authors.lastname: Hedley
authors.forename: K Ulrich
authors.initials: KU
authors.lastname: Petry
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber