Research is, in essence, the search for the truth. We ask ourselves clinical questions and we seek to find truthful answers: is streptomycin effective in the management of pulmonary tuberculosis? Is the combination of conservative surgery and radiation as effective as the radical mastectomy in local control of breast cancer? These questions have been definitively answered and have had an impact on clinical practice to the extent that millions of lives have been saved, and the morbidity of the most common cancer surgery in women has plummeted. These landmark discoveries, and many others, were realised by randomised controlled trials (RCTs).1,2
Before the turn of the millennium, the term ‘RCT’ was not in the verbiage of the orthopaedic surgeon. However, our research culture has shifted towards higher-level evidence and more and more studies published in the orthopaedic literature are RCTs, ranging from single, and smaller multicentre studies,3-15 to large multicentre national and international collaborative RCTs.16-21 Orthopaedic journals, including TheBone & Joint Journal and Bone & Joint Research, are now publishing at least one, if not several, RCTs per month. The methodology of the RCT is designed to minimise bias in answering research questions. As bias can be defined as systematic deviation from the truth, the least bias in the study design, the closer we will come to the truth when answering our research questions.
So why not answer all of our clinical research questions with an RCT? There are many barriers to conducting methodologically sound RCTs. Some are applicable to all medical specialties, and some are specific to surgical specialties. The former include cost and lack of expertise, infrastructure and clinical equipoise (the belief that treatment arms may in fact be equal in efficacy, and if they are not equal, the more efficacious could be either one). Although these barriers apply to all medical specialties, as surgeons we are further challenged by difficulty, if not impossibility, of blinding the patient and surgeon to treatment allocation, strong surgeon-specific preference and expertise, and the unwillingness of patients to be randomised.
Despite these barriers, the RCT has surfaced in orthopaedic research and is gaining momentum. What has made this possible despite the barriers? The reasons are likely multifactorial. Expanded education of the importance of RCTs in orthopaedic research, increased awareness, and the impetus to overcome barriers may be playing a role. Several orthopaedic surgeons have led by example and have developed collaborative research groups to work together to run multicentre RCTs.22 Surgeons have obtained advanced degrees in clinical research and have developed prospective research programmes at their own institutions. Orthopaedic surgeons are running and participating in RCTs more and more.
Models of innovative approaches to overcome the challenges of conducting RCTs abound in research in orthopaedic surgery. Feasibility has been addressed with several strategies. Surgeons have administered surveys to determine clinical equipoise and willingness to participate in a RCT.23,24 Small pilot studies address issues of recruitment and adherence to protocol.25,26 Even the publication of a well-designed protocol will increase awareness and interest in RCTs and inspire collaboration.27-29 In order to ensure adequate patient accrual, surgeons have conducted studies at multiple centres,30,31 or have even completed both arms in the same patient with two different procedures for bilateral hallux valgus.32 In order to ensure adequate follow-up and decrease study costs, others have designed and conducted studies in which the primary outcome requires only weeks or a few months of follow-up.33
Orthopaedic surgeons must be even more innovative in addressing issues of blinding and outcomes assessment. Visibly identical placebo arms can be used for regional anaesthetic injection, allowing for double-blind treatment allocation.11 Blinding can also be accomplished with a placebo arm in the evaluation of pulsed ultrasound efficacy in scaphoid fracture healing.34 Outcomes assessment can be blinded, independent and unbiased, particularly with respect to radiographic outcomes.18,35,36 Subtle differences in the type of implant available allow for blinding and, therefore, unbiased patient and outcomes assessment.37 Finally, the use of patient-centred outcomes can be independent of the opinion of the clinical practitioner and, as a result, provide an unbiased assessment of treatment efficacy.38
Despite the remarkable advances in research in orthopaedic surgery, there remain many challenges to overcome with respect to the conduct of RCTs. The majority of published orthopaedic research continues to be retrospective and non-comparative in nature. However, the ball is rolling, the inertia of low-level evidence is dissipating, and orthopaedic surgeons have the opportunity to join the ranks of other medical specialties in producing evidence that will truthfully guide our clinical practices. Keep on the ‘look out’ for upcoming volumes of The Bone & Joint Journal and Bone & Joint Research as we continue to publish orthopaedic RCTs and play our part in the research revolution in orthopaedic surgery.
1 No authors listed. Streptomycin Treatment of Pulmonary Tuberculosis. STREPTOMYCIN treatment of pulmonary tuberculosis Br Med J1948;2:769–782. Google Scholar
2 Black DM , MittendorfEA. Landmark trials affecting the surgical management of invasive breast cancer. Surg Clin North Am2013;93:501–518.CrossrefPubMed Google Scholar
3 Su EP , PernaM, BoettnerF, et al.A prospective, multi-center, randomised trial to evaluate the efficacy of a cryopneumatic device on total knee arthroplasty recovery. J Bone Joint Surg [Br]2012;94-A(Suppl):153–156.CrossrefPubMed Google Scholar
4 Schouten R , MaloneAA, TiffenC, FramptonCM, HooperG. A prospective, randomised controlled trial comparing ceramic-on-metal and metal-on-metal bearing surfaces in total hip replacement. J Bone Joint Surg [Br]2012;94:1462–1467.CrossrefPubMed Google Scholar
5 Mauffrey C , McGuinnessK, ParsonsN, AchtenJ, CostaML. A randomised pilot trial of ‘locking plate’ fixation versus intramedullary nailing for extra-articular fractures of the distal tibia. Bone Joint J2012;94-B:704–708. Google Scholar
6 Angadi DS , BrownS, CrawfurdEJP. Cemented polyethylene and cementless porous-coated acetabular components have similar outcomes at a mean of seven years after total hip replacement: a prospective randomised study. J Bone Joint Surg [Br]2012;94-B:1604–1610.CrossrefPubMed Google Scholar
7 Penny JO , BrixenK, VarmarkenJE, OvesenO, OvergaardS. Changes in bone mineral density of the acetabulum, femoral neck and femoral shaft, after hip resurfacing and total hip replacement: two-year results from a randomised study. J Bone Joint Surg [Br]2012;94-B:1036–1044.CrossrefPubMed Google Scholar
8 Kim Y- H , Park J-W, Kim J-S. Comparison of the Genesis II total knee replacement with oxidised zirconium and cobalt-chromium femoral components in the same patients: a prospective, double-blind, randomised controlled study. J Bone Joint Surg [Br]2012;94-B:1221–1227.CrossrefPubMed Google Scholar
9 Baliga S , McNairCJ, BarnettKJ, et al.Does circumpatellar electrocautery improve the outcome after total knee replacement?: a prospective, randomised, blinded controlled trial. J Bone Joint Surg [Br]2012;94-B:1228–1233.CrossrefPubMed Google Scholar
10 Thomsen MG , HustedH, BenckeJ, et al.Do we need a gender-specific total knee replacement? A randomised controlled trial comparing a high-flex and a gender-specific posterior design. J Bone Joint Surg [Br]2012;94-B:787–792.CrossrefPubMed Google Scholar
11 C Wyatt M , WrightT, LockerJ, 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
12 Wang Q , ZhangXL, ChenYS, ShenH, ShaoJJ. Resurfacing arthroplasty for hip dysplasia: a prospective randomised study. J Bone Joint Surg [Br]2012;94-B:768–773.CrossrefPubMed Google Scholar
13 Penning LIF , de BieRA, WalenkampGHIM. The effectiveness of injections of hyaluronic acid or corticosteroid in patients with subacromial impingement: a three-arm randomised controlled trial. J Bone Joint Surg [Br]2012;94-B:1246–1252.CrossrefPubMed Google Scholar
14 Jindal N , SankhalaSS, BachhalV. The role of fusion in the management of burst fractures of the thoracolumbar spine treated by short segment pedicle screw fixation: a prospective randomised trial. J Bone Joint Surg [Br]2012;94-B:1101–1106.CrossrefPubMed Google Scholar
15 Wallace DF , EmmettSR, KangKK, et al.The safety of peri-articular local anaesthetic injection for patients undergoing total knee replacement with autologous blood transfusion: a randomised trial. J Bone Joint Surg [Br]2012;94-B:1632–1636.CrossrefPubMed Google Scholar
16 Buckley R , LeightonR, TraskK. The Canadian Orthopaedic Trauma Society. J Bone Joint Surg [Br]2011;93-B:722–725.CrossrefPubMed Google Scholar
17 Leighton RK , TraskK. The Canadian Orthopaedic Trauma Society: a model for success in orthopaedic research. Injury2009;40:1131–1136.CrossrefPubMed Google Scholar
18 Bhandari M , GuyattG, Tornetta PIII, et al.Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures Investigators. Randomized trial of reamed and unreamed intramedullary nailing of tibial shaft fractures. J Bone Joint Surg [Am]2008;90-A:2567–2578. Google Scholar
19 Sanders DW , TieszerC, CorbettB. Canadian Orthopedic Trauma Society. Operative versus nonoperative treatment of unstable lateral malleolar fractures: a randomized multicenter trial. J Orthop Trauma2012;26:129–134. Google Scholar
20 Buckley R , LeightonR, SandersD, et al.Open reduction and internal fixation compared with ORIF and primary subtalar arthrodesis for treatment of Sanders type IV calcaneal fractures: a randomized multicenter trial. J Orthop Trauma2014;28:577–583.CrossrefPubMed Google Scholar
21 No authors listed. Canadian Orthopaedic Trauma Society. Nonoperative treatment compared with plate fixation of displaced midshaft clavicular fractures. A multicenter, randomized clinical trial J Bone Joint Surg [Am]2007;89-A:1–10. Google Scholar
22 Rangan A , JeffersonL, BakerP, CookL. Clinical trial networks in orthopaedic surgery. Bone Joint Res2014;3:169–174.CrossrefPubMed Google Scholar
23 Hasan K , RacanoA, DeheshiB, et al.Prophylactic antibiotic regimens in tumor surgery (PARITY) survey. BMC Musculoskelet Disord2012;13:91.CrossrefPubMed Google Scholar
24 Palmer AJR , ThomasGER, PollardTCB, et al.The feasibility of performing a randomised controlled trial for femoroacetabular impingement surgery. Bone Joint Res2013;2:33–40.CrossrefPubMed Google Scholar
25 Kearney RS , ParsonsN, CostaML. Achilles tendinopathy management: A pilot randomised controlled trial comparing platelet-richplasma injection with an eccentric loading programme. Bone Joint Res2013;2:227–232.CrossrefPubMed Google Scholar
26 Hogendoorn S , DuijnisveldBJ, van DuinenSG, et al.Local injection of autologous bone marrow cells to regenerate muscle in patients with traumatic brachial plexus injury: a pilot study. Bone Joint Res2014;3:38–47.CrossrefPubMed Google Scholar
27 Ghert M , DeheshiB, HoltG, et al.PARITY Investigators. Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study. BMJ Open2012;2:2. Google Scholar
28 Carr AJ , ReesJL, RamsayCR, et al.Protocol for the United Kingdom Rotator Cuff Study (UKUFF): a randomised controlled trial of open and arthroscopic rotator cuff repair. Bone Joint Res2014;3:155–160.CrossrefPubMed Google Scholar
29 Palmer AJR , Ayyar-GuptaV, DuttonSJ, et al.Protocol for the Femoroacetabular Impingement Trial (FAIT): a multi-centre randomised controlled trial comparing surgical and non-surgical management of femoroacetabular impingement. Bone Joint Res2014;3:321–327.CrossrefPubMed Google Scholar
30 Zhang X , LiY, WenS, et al.Carpal tunnel release with subneural reconstruction of the transverse carpal ligament compared with isolated open and endoscopic release. Bone Joint J2015;97-B:221–228.CrossrefPubMed Google Scholar
31 Bhandari M , GuyattG, Tornetta PIII, et al.Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures Investigators. Randomized trial of reamed and unreamed intramedullary nailing of tibial shaft fractures. J Bone Joint Surg [Am]2008;90-A:2567–2578. Google Scholar
32 Lee KB , ChoNY, ParkHW, SeonJK, LeeSH. A comparison of proximal and distal Chevron osteotomy, both with lateral soft-tissue release, for moderate to severe hallux valgus in patients undergoing simultaneous bilateral correction: a prospective randomised controlled trial. Bone Joint J2015;97-B:202–207.CrossrefPubMed Google Scholar
33 Dojode CM . A randomised control trial to evaluate the efficacy of autologous blood injection versus local corticosteroid injection for treatment of lateral epicondylitis. Bone Joint Res2012;1:192–197.CrossrefPubMed Google Scholar
34 Hannemann PFW , van WezenbeekMR, KolkmanKA, et al.CT scan-evaluated outcome of pulsed electromagnetic fields in the treatment of acute scaphoid fractures: a randomised, multicentre, double-blind, placebo-controlled trial. Bone Joint J2014;96-B:1070–1076.CrossrefPubMed Google Scholar
35 Abane L , AnractP, BoisgardS, et al.A comparison of patient-specific and conventional instrumentation for total knee arthroplasty: a multicentre randomised controlled trial. Bone Joint J2015;97-B:56–63.CrossrefPubMed Google Scholar
36 Kendrick BJL , KapteinBL, ValstarER, et al.Cemented versus cementless Oxford unicompartmental knee arthroplasty using radiostereometric analysis: a randomised controlled trial. Bone Joint J2015;97-B:185–191.CrossrefPubMed Google Scholar
37 Hamilton DF , BurnettR, PattonJT, et al.Implant design influences patient outcome after total knee arthroplasty: a prospective double-blind randomised controlled trial. Bone Joint J2015;97-B:64–70.CrossrefPubMed Google Scholar
38 Ketola S , LehtinenJ, RousiT, et al.No evidence of long-term benefits of arthroscopicacromioplasty in the treatment of shoulder impingement syndrome: five-year results of a randomised controlled trial. Bone Joint Res2013;2:132–139.CrossrefPubMed Google Scholar
