Trial of management of borderline and other low-grade abnormal smears (TOMBOLA): Trial design.
Cervical screening reduces the risk of cervical cancer by detecting and treating cervical intraepithelial neoplasia (CIN). The management of women with low-grade cervical abnormalities is controversial. Two management policies exist: repeat smears in primary care and colposcopy examination. It is not clear which of these is the more effective and efficient. There is also uncertainty as to the most effective and efficient management of women at colposcopy when an area of abnormality is seen on the cervix - immediate treatment or biopsy and selective recall for treatment if the biopsy result suggests this is necessary. The result of a human papillomavirus (HPV) test might assist in deciding the appropriate management of women with low-grade abnormalities. TOMBOLA, a pragmatic randomised-controlled trial set within the cervical screening programmes in Scotland and England, addresses these three areas of uncertainty. Almost four and a half thousand women aged 20-59 with a low-grade cervical abnormality have been recruited and randomised to either repeat smears or colposcopy examination. Women in the colposcopy arm of the trial are further randomised to a policy of either immediate treatment or biopsy and selective recall for treatment if they have an abnormal transformation zone. Women are followed up to an exit examination at 3 years. HPV testing is undertaken at recruitment and at the exit examination. The primary endpoint is cumulative incidence of CIN2/3. A range of other clinical, psychosocial and economic outcomes is being considered. This paper describes the design of the trial, and discusses the rationale underlying aspects of the design and the challenges faced in designing and implementing the trial.
Cotton
Seonaidh C
SC
Department of Public Health, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UK. s.c.cotton@abdn.ac.uk
Sharp
Linda
L
Little
Julian
J
Duncan
Ian
I
Alexander
Lindyanne
L
Cruickshank
Margaret E
ME
Gray
Nicola M
NM
Jenkins
David
D
Philips
Zoë
Z
Robertson
Alistair
A
Seth
Rashmi
R
D052685:Alphapapillomavirus / Q000302:isolation & purification; D003127:Colposcopy; D004739:England; D005260:Female; D006801:Humans; D017063:Outcome Assessment, Health Care; D030361:Papillomavirus Infections / Q000175:diagnosis; D011785:Quality Assurance, Health Care; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D012606:Scotland; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000628:therapy; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D014626:Vaginal Smears