Less and better surgical research needed: using pilot & - PowerPoint PPT Presentation

Less and better surgical research needed: using pilot & feasibility work to optimise trial design Jane M Blazeby Professor of Surgery, University of Bristol Honorary Consultant Surgeon, University Hospitals Bristol NHS Foundation Trust

What is a successful RCT in surgery?

Methodological & cultural challenges

How to use pilot & feasibility work to optimise a main (successful) RCT?

Definitions of pilot & feasibility studies 1. Feasibility study 2. Pilot study

Feasibility study Pieces of research done before a main study in order to answer the question “Can this study be done ?”

Pilot study (usually randomised) A version of the main study that is run in miniature to test whether the components of the main study can all work together

Components assessed in P & F work For example… No. of patients screened, eligible & randomised Application of inclusion & exclusion criteria Outcome measures (& blinding) Data collection (e.g. systems, forms, attrition) Intervention & co-interventions The team….

Purpose of pilot & feasibility studies • To study the difference between treatments to get an idea if the new intervention works. No! • To establish if the main trial is possible • To optimise the design of the main trial • To work out key issues around feasibility

“A comparison of procedures such as gastric bypass with adjustable gastric band ing, would be desirable.... .....however, this may not be possible because of expert opinion”

Uncertainties • Recruitment • Adherence to allocated treatment & cross over Avery KNL et al. (2015) Optimising the design of internal pilot work to inform efficient randomised controlled trials: issues to consider when developing progression criteria. Trials 16 (suppl. 2): P10.

Designed with an internal pilot phase

The By-Band Study Eligible for By-Band (60%) Bypass Band N=362 N=362 Establish feasibility in two centres with an internal pilot and QuinteT Recruitment Intervention

Progression criteria • Funder & trial team agree in advance • Reviewed at set time point • Stop main trial if not viable

Criteria set • Recruit • Screen 400 pts in 2 years • 60% of all patient eligible • Randomise 30% & then 50% (i.e.79 patients) • < 5% crossover

Surgeons recruiting into By-Band

Recruitment at end of internal pilot Oct 12 Jan 14

Recruitment after 8 months Recruitment feedback Recruitment investigation Oct 12

How did we do? • Recruit • Screened 330 (target 400) pts in 2 years • 65% (target 60%) eligible • Randomised 80 (target 79) • 3.5% (target 5%) crossover

Pilot (2012) to main RCT (2014)

Expanded into 11 UK centres

Current recruitment (11 centres)

Musgrove Park Hospital, Taunton University Hospital, Southampton Bournemouth & Christchurch Hospital St James Hospital, Leeds Richard Nicki James Amy Nick Claire Jeremy Catherine Welbourn Salter Byrne Long Davies Woods Hayden Moriarty City Hospitals, Sunderland Royal Cornwall Hospital, Truro Birmingham Heartlands Hospital Neil Paul Ian Jackie Rishi Sally Jennings Corrigan Finlay Dingle Singhal Abbott Royal Derby Hospital Queen Alexandra Portsmouth Homerton University Hospital St Marys Hospital, Imperial Paul Alison Nick Tracey Sanjay Marites Ahmed R. Jasmine Leeder Paton Carter Lee Agrawal Montemayor Ahmed Jose

Purpose of pilot & feasibility studies • To establish if the main trial is possible • To optimise the design of the main trial • To work out key issues around feasibility

Feasibility study: Phase A & B Feasibility Study (funded) Not (yet) funded Phase A Phase B Phase C Which interventions? Pilot RCT Main RCT What outcome measures? And other things…. ‘Nothing’ Simple Complex

Case studies Understand current practice Explore views of stakeholders

What is a ‘dressing’? • Inconsistencies in what is considered as a ‘dressing’ • Is glue a dressing? School of SOCIAL AND COMMUNITY MEDICINE

Relevance of ‘simple & complex’ I’ve never heard of the terms [simple and Surgeon 1016 complex] in terms of dressings. The vast majority ……have got a simple covering over the wound. Nurse 1002

Survey details • Prospective, in theatre • 14 days • Emergency/elective � • Upper/lower GI 21 centres 727 patients 1794 wounds

Patients n = 727 (%) Sex Female 375 (52) Age <30 118 (16) 30-50 193 (26) 51-70 253 (35) 71+ 158 (22) Diabetes 62 (9) BMI <20 50 (7) 20-25 275 (39) 26-30 238 (34) 30+ 141 (20) 8 (1) UGI Oesophagogastric 11 (2) Pancreaticobiliary Anti-reflux surgery 10 (1) Bariatric surgery 11 (2) Cholecystectomy 153 (21) 82 (11) LGI Colectomy 10 (1) Hartmanns procedure 40 (6) Rectal resection 48 (6) Stoma Hernia repair 128 (17) General Appendicectomy 109 (15) Laparoscopy 20 (3) 17 (2) Small bowel 76 (10) Other

Survey of dressings: types used n = 1794 (%) Simple 1203 (68) Advanced/complex 18 (1) Tissue adhesive 485 (27) None 63 (4)

New design of pilot RCT (Phase B) Inclusion Criteria Aged 16 or over Elective or unplanned abdo. surgery or C. section Willing to participate and follow-up for 4-8 weeks Randomise Exclusion Criteria Abdominal or other major surgery in the last 3/12 Allergy to dressings Intention to close the wound with tissue adhesive Surgery with no skin incision Lack of ability to read/understand English ‘No’ Any type of Any type of simple dressing tissue adhesive dressing “As -a- dressing” e.g. Opsite etc.

Feasibility study: Phase A & B Feasibility Study (funded) Not (yet) funded Phase A Phase B Phase C Which interventions? Pilot RCT Main RCT What outcome measures? And other things….

SSI: Outcome measures Additional treatment Serous discharge Erythema Purulent exudate Separation of deep tissue Isolation of bacteria Stay as inpatient >14 days

Bluebelle SSI measure • Developed from the literature • Interviews with patients and staff • Pre-testing and validation

Validation study design Recruitment Patient self assessment postal questionnaires Follow up clinical assessments 1. By telephone: Bluebelle observer SSI assessment 2. Face to face: reference SSI assessment (CDC criteria)

Planned analysis 1. Patient reported SSI assessment 2. Observer SSI assessment 3. Reference SSI assessment Recruited 415 pts (Bristol & Bham)

What other outcomes are relevant? Developed measures of: i) Practical wound management ii) Patient wound experience

Feasibility study: Phase A & B Feasibility Study (funded) Not (yet) funded Phase A Phase B Phase C Which interventions? Pilot RCT Main RCT What outcome measures? And other things….

Questions for the pilot RCT (Phase B) • Is it possible to recruit? • Is it practical & acceptable to randomise in theatre? • Is there adherence to the treatment allocation? • Can we validate the outcome measures? • Can we (and do we want to) design Phase C • Examine rates of SSI for types of dressing?

Progress with pilot RCT • 136 screened • 95 (69%) eligible • 65 randomised • No cross overs

Summary – benefits to P & F work • Non randomised feasibility work is an essential precursor to definitive trials • Internal pilot – good idea for all/most trials • External pilot - if major uncertainties about main trial

Acknowledgements • The ROMIO, By-Band-Sleeve and Bluebelle studies are funded by the NIHR HTA Programme (10/50/65, 14/140/78, 09/127/53 and 12/200/04 respectively) • The MRC ConDuCT-II Hub for Trials Methodology Research (www.bristol.ac.uk/social-community-medicine/ centres/conduct2) Email: j.m.blazeby@bris.ac.uk Department of Health Disclaimer: The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR HTA, NHS or the Department of Health.