Condition category
Urological and Genital Diseases
Date applied
25/10/2000
Date assigned
25/10/2000
Last edited
18/09/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.tombola.ac.uk/index.shtml

Contact information

Type

Scientific

Primary contact

Dr Julian Little

ORCID ID

Contact details

Department of Medicine & Therapeutics
University of Aberdeen
Foresterhill House Annex
Foresterhill
Aberdeen
AB25 2ZD
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

G9700808

Study information

Scientific title

Trial of management of borderline and other low-grade abnormal smears

Acronym

TOMBOLA

Study hypothesis

The purpose of this randomised trial is:
1. To determine whether a policy of cytological surveillance or initial colposcopy is the more effective and efficient policy for further investigation and clinical management in women with borderline abnormality or mild dyskaryosis.
2. To determine whether, following colposcopic examination of women with mild or borderline dyskaryosis, immediate LLETZ or biopsy and recall if appropriate for LLETZ, is the more effective and efficient method of treatment.
3. To evaluate the contribution of human papilloma virus (HPV) testing to the effectiveness and efficiency of the existing procedures for management of women with mild or borderline dyskaryosis

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Obstetrics and gynaecology

Intervention

Interventions updated as of 14/02/2007:
1. Cytological surveillance versus initial colposcopy (R1)
2. Immediate large loop excision of the transformation zone (LLETZ) versus biopsy and selective recall for LLETZ (R2)

Interventions provided at time of registration:
Cytological surveillance/initial colposcopy

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Primary outcomes relating to effectiveness:
1. Cumulative incidence of CIN2 and CIN3 or more severe disease (referred to as CIN2/3), as determined by biopsy, up to and including the exit examination conducted three years after enrolment
2. Point prevalence of CIN2/3, as determined by biopsy at the exit examination conducted three years after enrolment
3. For medium-term psychosocial effects of cytological surveillance versus initial colposcopy, cumulative proportion of clinically significant anxiety and/or depression, as determined by the Hospital Anxiety and Depression Scale (HADS), during the 34 month period after enrolment in the trial
4. For short-term psychosocial effects of immediate LLETZ versus biopsy and selective recall for LLETZ, (a) mean impact of events score, as determined by the Impact of Events Scale (IES) and (b) proportion of clinically significant anxiety and/or depression as determined by the HADS, at nine weeks after the initial colposcopy

Outcomes relating to efficiency:
1. Health related quality of life
2. Total Health Service resource use
3. Non-NHS costs

Secondary outcome measures

Not provided at time of registration

Overall trial start date

14/06/1999

Overall trial end date

31/05/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. An index smear which indicates mild dyskaryosis, or an index smear which indicates borderline dyskaryosis and a repeat smear taken 6 months later which shows borderline or mild dyskaryosis
2. Resident in Grampian Health Board Area, Tayside Health Board Area or in the Nottingham area with their smear processed by the Nottingham Cervical Screening Laboratory
3. Aged 20-59 years
4. Prior to the index smear, not have had an abnormal smear within the past 3 years
5. Not have had previous treatment for suspected cervical lesions
6. Not be pregnant
7. Not intend to move from the trial areas in the 3-year period following enrolment

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Modified 13/08/2009: Originally 10,000. Revised following changes to the eligibility criteria to 4483 (agreed by TSC in May 2000, ratified by MRC in January 2001)

Participant exclusion criteria

Exclusions from R2: If colposcopy is unsatisfactory because the squamo-columnar junction is not visible, the woman will not be randomised but will be treated according to local clinical practice

Recruitment start date

14/06/1999

Recruitment end date

31/05/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Aberdeen
Aberdeen
AB25 2ZD
United Kingdom

Sponsor information

Organisation

Medical Research Council (MRC) (UK)

Sponsor details

20 Park Crescent
London
W1B 1AL
United Kingdom
+44 20 7636 5422
clinical.trial@headoffice.mrc.ac.uk

Sponsor type

Research council

Website

http://www.mrc.ac.uk

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2006 protocol in http://www.ncbi.nlm.nih.gov/pubmed/16765101
2. 2006 reasons for participation in http://www.ncbi.nlm.nih.gov/pubmed/17060217
3. 2009 results on cytological surveillance versus initial colonoscopy in http://www.ncbi.nlm.nih.gov/pubmed/19638646
4. 2009 results on large loop excision versus biopsy and selective recall in http://www.ncbi.nlm.nih.gov/pubmed/19638647
5. 2009 results on cost effectiveness in http://www.ncbi.nlm.nih.gov/pubmed/19638648
6. 2009 results on comparison of EQ-5D and HADS in http://www.ncbi.nlm.nih.gov/pubmed/19811595
7. 2010 management of low-grade results in http://www.ncbi.nlm.nih.gov/pubmed/20374607
8. 2011 psychosocial impact results in http://www.ncbi.nlm.nih.gov/pubmed/21179033
9. 2012 default from follow-up results in http://www.ncbi.nlm.nih.gov/pubmed/21366734
10. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22921577
11. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/24386076
12. 2015 results in http://www.ncbi.nlm.nih.gov/pubmed/26376822

Publication citations

  1. Results on cytological surveillance versus initial colonoscopy

    Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities: multicentre randomised controlled trial., BMJ, 2009, 339, b2546.

  2. Results on large loop excision versus biopsy and selective recall

    Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial., BMJ, 2009, 339, b2548.

  3. Results on cost effectiveness

    Options for managing low grade cervical abnormalities detected at screening: cost effectiveness study., BMJ, 2009, 339, b2549.

  4. Psychosocial impact results

    Sharp L, Cotton S, Gray N, Avis M, Russell I, Walker L, Waugh N, Whynes D, Woolley C, Thornton A, Smart L, Cruickshank M, Little J, , Long-term psychosocial impact of alternative management policies in women with low-grade abnormal cervical cytology referred for colposcopy: a randomised controlled trial., Br. J. Cancer, 2011, 104, 2, 255-264, doi: 10.1038/sj.bjc.6606042.

  5. Results

    Sharp L, Cotton S, Thornton A, Gray N, Cruickshank M, Whynes D, Duncan I, Hammond R, Smart L, Little J, Who defaults from colposcopy? A multi-centre, population-based, prospective cohort study of predictors of non-attendance for follow-up among women with low-grade abnormal cervical cytology., Eur. J. Obstet. Gynecol. Reprod. Biol., 2012, 165, 2, 318-325, doi: 10.1016/j.ejogrb.2012.08.001.

  6. Results

    Sharp L, Cotton S, Little J, Gray NM, Cruickshank M, Smart L, Thornton A, Waugh N, Walker L, , psychosocial impact of alternative management policies for low-grade cervical abnormalities: results from the TOMBOLA randomised controlled trial., PLoS ONE, 2013, 8, 12, e80092, doi: 10.1371/journal.pone.0080092.

  7. Cotton SC, Sharp L, Little J, Duncan I, Alexander L, Cruickshank ME, Gray NM, Jenkins D, Philips Z, Robertson A, Seth R, , Trial of management of borderline and other low-grade abnormal smears (TOMBOLA): Trial design., Contemp Clin Trials, 2006, 27, 5, 449-471, doi: 10.1016/j.cct.2006.04.001.

  8. Sharp L, Cotton SC, Alexander L, Williams E, Gray NM, Reid JM, , Reasons for participation and non-participation in a randomized controlled trial: postal questionnaire surveys of women eligible for TOMBOLA (Trial Of Management of Borderline and Other Low-Grade Abnormal smears)., Clin Trials, 2006, 3, 5, 431-442, doi: 10.1177/1740774506070812.

  9. Whynes DK, , Responsiveness of the EQ-5D to HADS-identified anxiety and depression., J Eval Clin Pract, 2009, 15, 5, 820-825, doi: 10.1111/j.1365-2753.2008.01102.x.

  10. Cotton S, Sharp L, Little J, Cruickshank M, Seth R, Smart L, Duncan I, Harrild K, Neal K, Waugh N, , The role of human papillomavirus testing in the management of women with low-grade abnormalities: multicentre randomised controlled trial., BJOG, 2010, 117, 6, 645-659, doi: 10.1111/j.1471-0528.2010.02519.x.

  11. Sharp L, Cotton S, Thornton A, Gray N, Whynes D, Smart L, Waugh N, Duncan I, Cruickshank M, Little J, , Which women default from follow-up cervical cytology tests? A cohort study within the TOMBOLA trial., Cytopathology, 2012, 23, 3, 150-160, doi: 10.1111/j.1365-2303.2011.00848.x.

  12. Results

    Sharp L, Cotton S, Cruickshank M, Gray N, Smart L, Whynes D, Little J; TOMBOLA Group, Impact of post-colposcopy management on women's long-term worries: results from the UK population-based TOMBOLA trial, J Fam Plann Reprod Health Care, 2015 , doi: 10.1136/jfprhc-2015-101170.

Additional files

Editorial Notes