EURURO Vol. 71 No. 5

Platinum Priority – Editorial

Referring to the article published on pp. 811–819 of this issue

In Defense of Randomized Clinical Trials in Surgery:

Let Us Not Forget Archie Cochrane’s Legacy

James W.F. Catto

a , * ,

Jane M. Blazeby

b ,

Lars Holmberg

c , d ,

Freddie C. Hamdy

e ,

Julia Brown

Academic Urology Unit, University of Sheffield, Sheffield, UK;

Bristol Centre for Surgical Research, University of Bristol, Bristol, UK;

Faculty of Life Sciences

and Medicine, Kings College London, London, UK;

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;

Nuffield Department of Surgical

Sciences, University of Oxford, Oxford, UK;

Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK

The Cochrane collaboration is a pinnacle of evidence-based

medicine. It acts to commission, improve, and collate the

best medical evidence for clinicians. Its creation followed

work by the Scottish physician and epidemiologist Archi-

bald Cochrane. He recognized that high-quality reproduc-

ible evidence in properly designed studies was vital to

facilitate medical advances. His monograph

Effectiveness

and Efficiency: Random Reflections on Health Services

explained his beliefs that randomized controlled trials

acted as a brake on health care inflation

[1]

Cochrane painted clinicians as conspirators in health care

inflation by failing to undertake trials or ignoring results that

do not fit preconceived ideas. This description should be

unrecognizable inmodern times. Many of us have contributed

to randomized trials, and all of us practice in an era of

evidence-basedmedicine. However, there aremany questions

that randomized controlled trials (RCTs) are not answering,

and the percentage of these is greater in surgery than in other

specialties

[2]

. While this may reflect legitimate difficulties in

intervention standardization and procedural variations, the

context for intervention delivery, and challenges in blinding

and recruitment, the surgical culture does not help

[3] .

Many

methodological difficulties can be overcome via robust

statistical design, training of the surgical research workforce,

and breaking down of cultural barriers. In the UK, the Royal

College of Surgeons recently developed a network of centers

with expertise to address these issues, and major funding

bodies have made surgical trials a priority. This initiative is

working well, and the number of funded and successfully run

RCTs in surgery has dramatically increased.

It is essential to manage patients in accordance with the

best evidence. The creation of this evidence is key, with

systematic reviews (SRs) and meta-analyses (MAs) produc-

ing the strongest data. However, SRs and MAs depend on

good-quality trials. Both can flatter to deceive if the quality

of the baseline evidence is low. As RCTs and SRs become

more prevalent, we are increasingly facing a new paradox:

(1). an RCT cannot be started because of lack of preliminary

evidence of effectiveness, and (2) this evidence is produced

via numerous non-randomized studies, then (iii) an RCT is

performed and delivers a result that conflicts with the prior

evidence. In this issue of

European Urology

, Richard

Sylvester and colleagues from the European Association

of Urology Guidelines Office discuss this paradox

[4]

. The

authors state that RCTs are the gold standard of evidence

that should be believed above all else. However, as for MAs,

RCTs reflect their design and content. RCTs can be

susceptible to bias by design, chance, or interpretation.

The authors discuss contemporary examples for which RCTs

conflict with prior data

[4] .

The conflict for medical

expulsive therapy appears to arise from prior reports

combining small studies with various endpoints. The

authors accept the large, well-constructed, prospective

RCT, despite concerns about extrapolation of findings into

subgroups. A different explanation is apparent for the

partial nephrectomy conflict, which appears to arise from

prior low-power retrospective studies and an RCT with low

event rates and frequent arm crossover from the intention-

to-treat analysis. This leaves the question still open and

needing more robust trials.

E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 8 2 0 – 8 2 1

available at

www.scienced irect.com

journal homepage:

www.europeanurology.com

DOI of original article:

http://dx.doi.org/10.1016/j.eururo.2016.11.023

* Corresponding author. Academic Urology Unit, University of Sheffield, Institute for Cancer Studies, The Medical School, Beech Hill Road, Sheffield

S10 2RX, UK. Tel. +44 114 2268840; Fax: +44 114 2712268.

E-mail address:

j.catto@sheffield.ac.uk

(James W.F. Catto).

http://dx.doi.org/10.1016/j.eururo.2016.12.029

0302-2838/

2017 Published by Elsevier B.V. on behalf of European Association of Urology.