The randomised controlled trial (RCT) is considered the benchmark approach to determine the comparative efficacy of various clinical interventions. Rigorously designed RCTs are powered to detect a difference in a pre-defined primary outcome. Other secondary outcomes may be explored, but with the caveat that the study may not be powered to detect a difference between treatment groups for the secondary outcomes. Primary and secondary outcomes should be clearly specified and defined at the time of trial registration on ClinicalTrials.gov. This allows for accountability in reporting of the outcomes once the study is complete and the results are published.
It has become apparent in the surgical and orthopaedic literature that pre-registration of RCTs suffer from deficiencies,1 and that there are inconsistencies between the primary outcome registered and the primary outcome reported.2This may occur because the findings for the primary outcome were not found to be statistically significant, and therefore the authors report any positive secondary outcome finding in lieu of reporting the primary outcome. This maneuvering of outcomes is termed ‘spin’ and is common in the medical literature.3 However, primary outcomes may indeed be negative4-7 and secondary outcomes may be positive, and can legitimately be reported as such.8,9 Transparent registering and reporting of outcomes, whether negative or positive, can alleviate the tendency to ‘spin’ results.
The candid reporting of outcomes in RCTs is imperative for various reasons. Outcomes may have an effect on patient management.10-12 In addition, reported outcomes can help design future RCTs, with and without patient involvement in protocol development.13,14 However, not all outcomes need to be considered primary or secondary. Smaller feasibility trials can be exploratory and report multiple pre-defined outcomes;15 however in these exploratory studies, the authors should not specify a primary outcome and should indicate that the trial is meant to generate hypotheses for further larger trials. Pilot RCTs are another form of RCT that do not report primary outcomes, but instead report feasibility metrics such as recruitment and protocol adherence.16-18
However, in the case of adequately powered RCTs with a pre-defined primary outcome, it is the responsibility of the authors to report the primary outcome with minimal bias. A blinded and independent central adjudication committee can adjudicate all clinically significant outcomes, both primary and secondary, in order to maintain the integrity of the outcomes reporting and minimise bias in outcomes assessment.19 For these large RCTs, clear and transparent reporting of outcomes will allow the data reported to be included in meta-analyses,20,21 which are the most likely study types to be considered in clinical practice guidelines and drive change in clinical practice.
Outcomes reporting in RCTs can be a complex and tricky business. Because orthopaedic surgeons are busy clinicians, often only the conclusions of an RCT will be quickly digested, and the methodology considered a less important read. However, a quick cross reference on ClinicalTrials.gov can determine that the primary outcome reported was pre-defined, and that the primary and secondary outcomes were not ‘switched’ in the reporting process. Such a rapid check as can instill confidence in the findings of the RCT and therefore improve translation of the findings into clinical practice when practice change is feasible and supported by biological rationale and patient preferences.
None declared
None declared
References
1 Hannink G , Gooszen HG , Rovers MM . Comparison of registered and published primary outcomes in randomized clinical trials of surgical interventions. Ann Surg2013;257:818-823.CrossrefPubMed Google Scholar
2 Rongen JJ , Hannink G . Comparison of Registered and Published Primary Outcomes in Randomized Controlled Trials of Orthopaedic Surgical Interventions. J Bone Joint Surg [Am]2016;98-A:403-409.CrossrefPubMed Google Scholar
3 Arunachalam L , Hunter IA , Killeen S . Reporting of Randomized Controlled Trials With Statistically Nonsignificant Primary Outcomes Published in High-impact Surgical Journals. Ann Surg2017;265:1141-1145.CrossrefPubMed Google Scholar
4 Waterson HB , Clement ND , Eyres KS , Mandalia VI , Toms AD . The early outcome of kinematic versus mechanical alignment in total knee arthroplasty: a prospective randomised control trial. Bone Joint J2016;98-B:1360-1368.CrossrefPubMed Google Scholar
5 van Tilburg CWJ , Stronks DL , Groeneweg JG , Huygen FJPM . Randomised sham-controlled double-blind multicentre clinical trial to ascertain the effect of percutaneous radiofrequency treatment for lumbar facet joint pain. Bone Joint J2016;98-B:1526-1533.CrossrefPubMed Google Scholar
6 Huijbregts HJ , Khan RJ , Fick DP , et al. Component alignment and clinical outcome following total knee arthroplasty: a randomised controlled trial comparing an intramedullary alignment system with patient-specific instrumentation. Bone Joint J2016;98-B:1043-1049.CrossrefPubMed Google Scholar
7 Boonen B , Schotanus MGM , Kerens B , et al. No difference in clinical outcome between patient-matched positioning guides and conventional instrumented total knee arthroplasty two years post-operatively: a multicentre, double-blind, randomised controlled trial. Bone Joint J2016;98-B:939-944.CrossrefPubMed Google Scholar
8 Wyatt MC , Wright T , Locker J , et al. Femoral nerve infusion after primary total knee arthroplasty: a prospective, double-blind, randomised and placebo-controlled trial. Bone Joint Res2015;4:11-16.CrossrefPubMed Google Scholar
9 Yuenyongviwat V , Iamthanaporn K , Hongnaparak T , Tangtrakulwanich B . A randomised controlled trial comparing skin closure in total knee arthroplasty in the same knee: nylon sutures versus skin staples. Bone Joint Res2016;5:185-190.CrossrefPubMed Google Scholar
10 Dean BJF , Jones LD , Palmer AJR , et al. A review of current surgical practice in the operative treatment of proximal humeral fractures: does the PROFHER trial demonstrate a need for change? Bone Joint Res 2016;5:178-184.CrossrefPubMed Google Scholar
11 Costa ML , Jameson SS , Reed MR . Do large pragmatic randomised trials change clinical practice?: assessing the impact of the Distal Radius Acute Fracture Fixation Trial (DRAFFT). Bone Joint J2016;98-B:410-413.CrossrefPubMed Google Scholar
12 Fullilove S , Gozzard C . Dorsally displaced fractures of the distal radius: a critical appraisal of the DRAFFT (distal radius acute fracture fixation trial) study. Bone Joint J2016;98-B:298-300.CrossrefPubMed Google Scholar
13 Handoll HHG , Brealey SD , Jefferson L , et al. Defining the fracture population in a pragmatic multicentre randomised controlled trial: PROFHER and the Neer classification of proximal humeral fractures. Bone Joint Res2016;5:481-489.CrossrefPubMed Google Scholar
14 Huxley C , Achten J , Costa ML , Griffiths F , Griffin XL . A process evaluation of the WHiTE Two trial comparing total hip artroplasty with and without dual mobility component in the treatment of displaced intracapsular fractures of the proximal femur: can a trial investigating total hip arthroplasty for hip fracture be delivered in the NHS?Bone Joint Res2016;5:444-452. Google Scholar
15 Karlakki SL , Hamad AK , Whittall C , et al. Incisional negative pressure wound therapy dressings (iNPWTd) in routine primary hip and knee arthroplasties: A randomised controlled trial. Bone Joint Res2016;5:328-337.CrossrefPubMed Google Scholar
16 Griffin XL , Parsons N , Achten J , Costa ML . A randomised feasibility study comparing total hip arthroplasty with and without dual mobility acetabular component in the treatment of displaced intracapsular fractures of the proximal femur : The Warwick Hip Trauma Evaluation Two : WHiTE Two. Bone Joint J. 2016;98-B:1431-1435.CrossrefPubMed Google Scholar
17 PARITY Investigators. Prophylactic antibiotic regimens in tumour surgery (PARITY): a pilot multicentre randomised controlled trial. Bone Joint Res2015;4:154-162.CrossrefPubMed Google Scholar
18 Chesser TJS , Fox R , Harding K , et al. The administration of intermittent parathyroid hormone affects functional recovery from trochanteric fractured neck of femur: a randomised prospective mixed method pilot study. Bone Joint J2016;98-B:840-845.CrossrefPubMed Google Scholar
19 Nuttall J , Evaniew N , Thornley P , et al. The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial. Bone Joint Res. 2016;5:347-352.CrossrefPubMed Google Scholar
20 Sabharwal S , Patel NK , Griffiths D , et al. Trials based on specific fracture configuration and surgical procedures likely to be more relevant for decision making in the management of fractures of the proximal humerus: findings of a meta-analysis.Bone Joint Res2016;5:470-480.CrossrefPubMed Google Scholar
21 Wilson DGG , Poole WEC , Chauhan SK , Rogers BA . Systematic review of aspirin for thromboprophylaxis in modern elective total hip and knee arthroplasty. Bone Joint J2016;98-B:1056-1061.CrossrefPubMed Google Scholar
