Improving RCTs in surgery: describing

Transcription

1 Improving RCTs in surgery: describing standardising & monitoring interventions Jane M Blazeby Professor of Surgery & Honorary Consultant Surgeon, Director MRC ConDuCT-II Hub for Trials Methodology Research Director Royal College of Surgeon of England Trials Centre

2 An uneven evidence base and therefore uneven practice

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4 Difficult to select outcomes

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6 Cultural issues in trials Surgeons are not team players Reluctance to admit uncertainty Attraction of innovation rather than evaluation Just no exposure to RCTs

7 Spend of the MRC/NIHR on research in 2008/9 Non-surgery Surgery

8 Number of Studies (1) Number of Studies Open and In Set-Up in 2008/ A paucity Specialty Group of surgical RCTs

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11 A new era to create a culture & provide an infrastructure for multidisciplinary research that contributes to significant changes in surgical services in the NHS and worldwide

12 Five Surgical trials centres Oxford Bristol Liverpool/Manchester Birmingham London Leads Prof Andrew Carr Prof Freddie Hamdy Prof Jane Blazeby Dr Chris Rogers Prof Nigel Bundred Prof Paula Ghaneh Prof Jon Deeks Prof Pam Kearns Prof Peter Sasieni Prof Iain Hutchinson

13 Surgical speciality leads Speciality Leads for: Breast Surgery Linked to associations Competitive process & funded 12++ appointments Orthopaedic Otolaryngology Transplantation Neurosurgery Cardiology Oral & maxillofacial Coloproctology Endocrine Upper GI Surgery Hand Surgery

14 Royal College of Surgeons Research Committee Clinical Trials Units Manchester Liverpool Birmingham Oxford Bristol Barts London Clinical Trials Units Surgical specialty leads Surgical specialty leads Surgical specialty leads Surgical specialty leads Speciality association e.g. Endocrine Speciality association e.g. Bariatric Society Speciality association e.g. AUGIS Trainee collaboratives

15 How it works Speciality lead Clinicians, meetings, ideas Royal College Surgical Trials Centre Registered Clinical Trials Unit

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17 Royal College of Surgeons & Medical Research Council Initiatives gical-research/surgical-clinical-trials

18 Hubs for Trials Methodology Research All-Ireland Hub Cambridge Biostatistics Unit Bristol ConDuCT-II Hub London MRC Clinical Trials Unit North West Hub Oxford Clinical Trials Service Unit All Ireland North West Bristol Oxford London Cambridge

19 Collaboration & Innovation in Difficult RCTs Invasive Interventions Prioritisation & trial design Optimising recruitment Methods for pilot studies & trial conduct Outcomes in trials & practice

20 Experience of RCTs in surgery all stand up Designed one Recruited at patient Analysed a surgical trial

21 How it works Speciality lead Clinicians, meetings, ideas Royal College Surgical Trials Centre Registered Clinical Trials Units & MRC Hub

22 A comparison of procedures... such as bypass with banding, would be desirable. However, this may not be possible because of expert opinion

23 Aim To compare the effectiveness of gastric bypass and adjustable gastric band

24 Original By-Band Design All surgical referrals screened Eligible for By-Band Web based automated central randomisation Exclusions Gastric surgery Large hiatus hernia Pregnancy Crohn s disease Cirrhosis SLE Bypass Band Internal pilot

25 Hamish Noble Jim Byrne Richard Welbourn David Mahon Richard Byrom Jez Hayden Nick Davies Abeezar Sarela Jamie Kelly

26 By-Band recruitment Target recruitment 60% eligible, 30% recruited in first 18 months, 50% thereafter

27 Recruitment Cross over Sleeve gastrectomy

28 8 RCTs of surgical interventions 3 Band vs. Bypass 7 Bypass vs. Sleeve 0 Band vs. Sleeve still a need for RCTs to examine outcomes over longer-time periods.

29 By-Band to By-Band-Sleeve

30 By-Band-Sleeve Design All surgical referrals screened Eligible for By-Band-Sleeve Web based automated central randomisation Exclusions Gastric surgery Large hiatus hernia Pregnancy Crohn s disease Cirrhosis SLE Sleeve Bypass Band

31 Target recruitment in By-Band -Sleeve Calculated as 60% eligible, 20% 30% recruited in first 12 months, 50% thereafter with training 45%

32 By-Band-Sleeve recruitment Target recruitment 60% eligible, 20% recruited in first 12 months, 45% thereafter

33 Other roles of Hub and trials centre

34 PhDs (advert now) Workshops

35 Collaborations with MRC Hubs Attended a specific workshop Funded collaboration with Hub member Attended the methodology conference

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40 Systematic review of reporting standards* Top 6 IF medical & surgical journals Two group RCTs of surgical interventions (n = 80) Descriptions of intervention Standardisation in the RCT Data extraction 4a descriptions of the intervention just the name of the operation or more detail reference of protocol/citation 4b interventions standardisation yes/no * Blencowe et al in press BJS 2015

41 Explanatory RCT

42 Pragmatic RCT

43 Systematic review of reporting standards A tension free mesh repair according to Lichtenstein Reporting standards n = 160 (%) Any description of surgical intervention 129* (80.6%) *50 papers made reference to citation, pictures or videos

44 Differences between the two groups?

45 Systematic review of reporting standards Reporting standard n = 160 (%) Standardisation of surgical intervention 47 (29.4)* *but 30 provided no details of how Operations were performed using standard techniques

46 A standard gastrectomy

47 Examples of standardisation n = 16 Pre-trial workshops for surgeons 5 Training videos/photos 4 Methods for standardisation were all limited to one sentence, except for one trial, which Detailed published operative a separate paper manual describing how standardisation 1 achieved 1 1 Frobell RB et al. RCT of treatment for acute anterior cruciate ligament tears. Peer review with visiting surgeon 1 NEJM 2010:363; Stated no standardisation required 5

48 Differences between pragmatic & explanatory Explanatory n=60 Pragmatic n=78 Intervention description 46 (76%) 63 (81%) Standardisation 21 (35%) 16(21%)

49 Interventions poorly described what ever the trial design What details are needed? What does this depend on?

50 Potential solution Design Identify the components and steps of interventions Consider how much description/standardisation to provide Conduct Deliver interventions in accordance with the descriptions Reporting Reporting in accordance with CONSORT recommendations

51 Components Context Concomitant interventions Non-technical skills Surgical intervention Technical expertise Patient selection

52 Aim To develop a typology to use during trial design for describing the components of a surgical interventions within RCTs

53 Methods Top 6 IF medical & surgical journals Two group RCTs of surgical interventions (n = 80) Detailed analysis or reports Developed a framework Modified it Re-applied it to the trial interventions Descriptions of intervention Standardisation in the RCT

54 Description of the surgical intervention

55 Three levels of description Descriptions What level of description? Entire intervention Components Steps

56 Typology Entire intervention Exploration Resection Reconstruction

57 Entire intervention Exploration Resection Reconstruction

58 Entire Entire intervention intervention Exploration Resection Reconstruction

59 Entire Entire intervention intervention Exploration Resection Reconstruction Your example here

60 Three levels of description Descriptions What level of description? Entire intervention Components Steps

61 Typology Components Incision and access Dissection Resection Reconstruction Insertion of surgical adjunct Intra-operative diagnosis Closure

62 Components Incision and access Dissection Resection Reconstruction Insertion of surgical adjunct Intra-operative diagnosis Closure

63 Three levels of description Descriptions What level of description? Entire intervention Components Steps

64 What type of standardisation? Standardisation When standardised? Entire intervention Components Steps What level of standardisation?

65 What type of standardisation? Entire intervention Mandatory Prohibited Optional According to the detailed protocol No deviation from the protocol It is at the surgeon s discretion

66 What type of standardisation? Component Mandatory Prohibited Optional The gall bladder must be removed in a bag No gall bladder bags to be removed It is at the surgeon s discretion whether or not to use a gallbladder bag

67 When is standardisation required? Component Under all circumstances Also fix the hernia Under some circumstances May also fix the hernia

68 What level of standardisation is required? What type of standardisation required When standardisation required Level of standardisation required Mandatory Under all circumstances Exactly Prohibited Under some circumstances Within boundaries Optional Flexibly

69 How will the framework be used? Trial design What are the components and steps? Feasibility work How much description/standardisation? Main trial Description/standardisation in trial manual

70 Factors that influence all the decisions

71 Royal College of Surgeons & Medical Research Council Initiatives gical-research/surgical-clinical-trials