Trends in Country-Specific Surgical Randomized Clinical Trial Publications

Abstract

This study examines the rate of and investment in publication of randomized clinical trials in surgery in the United States and abroad.

Historically, the United States was at the forefront of surgical discovery, as measured by publications and citations. A decline in surgical study publications was seen from 2000 to 2010, the drivers of which were hypothesized to be the external and internal pressures from stagnating US funding and the inefficiencies in translating funds into published work. Randomized clinical trials (RCTs) are vital to discovery. We describe trends in country-specific surgical RCT publications in preeminent international journals to generate and inform the dialogue between surgical researchers and funding agencies in the United States.

Methods

The tables of contents of the top 10 impact factor–ranked, non-subspecialty surgical journals were searched for RCTs published from January 1, 2003, to December 31, 2005, and from January 1, 2013, to December 31, 2015 and categorized by clinical focus and country origin. This study did not meet the criteria for institutional review board review as it did not involve human subjects research and used publicly available, published manuscripts. Data were collected from February 1, 2017, to June 1, 2017. Data analysis took place from June 1, 2017, to July 1, 2017.

Two of us (J.A.F. and S.M.W.) independently classified the trials into 12 categories on the basis of a clinical end point. Country of origin was defined by the study population or by the senior authors’ nationality. Trials after 2005 were excluded if they were not registered in a mandatory public trials registry acceptable to the International Committee of Medical Journal Editors. Trials by country were normalized to the number per 100 000 population and to the amount of government-only gross domestic spending on research and development (R&D). These ratios are proxy measurements for an individual country’s rate of publication and the efficiency of government spending on surgical R&D.

Results

In total, 659 RCTs met the inclusion criteria, of which 322 trials (48.8%) published between 2003 and 2005 and 337 trials (51.1%) published between 2013 and 2015. The number of published trials by journal for the periods 2003-2005 and 2013-2015 included The New England Journal of Medicine (48 and 46), JAMA (26 and 39), JAMA Surgery or Archives of Surgery (16 and 15), The Lancet (35 and 32), Lancet Oncology (3 and 14), Annals of Surgery (60 and 81), British Journal of Surgery (70 and 47), Journal of the American College of Surgeons (10 and 19), Diseases of the Colon & Rectum (47 and 19), and Annals of Surgical Oncology (7 and 25). Thirty-nine countries of origin were included, and 40 studies had multinational authorship. The most common clinical focus categories for the periods 2003-2005 and 2013-2015 included cancer (51 and 76), gastrointestinal surgery (115 and 74), critical care (14 and 33), and cardiovascular (51 and 32). The United States had the greatest number of studies (157 [23.8%]), but when the totals were adjusted for per capita population, the United Kingdom, Canada, and nearly all Western European countries published more trials (312 [47.3%]). The United States had the greatest direct government funding for R&D over both periods ($38.6 billion for 2003-2005 and $126.8 billion for 2013-2015), but this funding did not translate into published surgical RCTs. Globally, there was a decrease in the number of RCTs per government spending on R&D, with only Japan and Norway as outliers (Table).

Table. Breakdown of the Publication of RCTs by Country.

Country of Origin	RCTs Published in 2003-2005			RCTs Published in 2013-2015
	No. (%) (n = 322)	No. per 100 000 Populationa	No. per Billion USD Direct Government Spending on R&Db	No. (%) (n = 337)	No. per 100 000 Populationa	No. per Billion USD Direct Government Spending on R&Db
Europe
United Kingdom	39 (12.1)	0.07c	14.9c	45 (13.3)	0.07c	5.1c
Netherlands	26 (8.0)	0.16c	28.7c	34 (10.0)	0.2c	6.5c
France	12 (3.7)	0.02	2.2c	19 (5.6)	0.03	1.2c
Germany	15 (4.6)	0.02	1.9c	18 (5.3)	0.02	0.6
Italy	15 (4.6)	0.03c	5.3c	14 (4.1)	0.02	2.3c
Denmark	8 (2.4)	0.15c	32.8c	13 (3.8)	0.23c	14.4
Spain	10 (3.1)	0.02	6.4c	8 (2.3)	0.02	1.6c
Switzerland	3 (0.9)	0.04c	36.3c	8 (2.3)	0.1c	7.4c
Sweden	21 (6.5)	0.23c	51.3c	6 (1.7)	0.06c	2.6c
Finland	2 (0.6)	0.04c	5.2c	5 (1.4)	0.09c	4.0c
Norway	1 (0.3)	0.02	2.6c	4 (1.1)	0.08c	2.9c
Ireland	3 (0.9)	0.07c	22.8c	3 (0.8)	0.07c	4.2c
Belgium	0	NA	NA	2 (0.5)	0.02	0.7
Israel	4 (1.2)	0.06c	NA	2 (0.5)	0.02	3.2c
Poland	0	NA	NA	2 (0.5)	0.01	0.5
Czech Republic	0	NA	NA	1 (0.2)	0.01	0.5
Greece	2 (0.6)	0.02	9.3c	NA	NA	NA
Portugal	1 (0.3)	0.01	4.3c	NA	NA	NA
North America
United States	70 (21.7)	0.02	1.8	87 (25.8)	0.03	0.7
Canada	9 (2.7)	0.03c	4.8c	16 (4.7)	0.05c	2.4c
Guatemala	1 (0.3)	0.01	NA	NA	NA	NA
Mexico	1 (0.3)	0.0	0.8	NA	NA	NA
Asia-Pacific
Japan	3 (0.9)	0.0	0.3	19 (5.6)	0.02	1c
Australia	12 (3.7)	0.06	8.2c	9 (2.6)	0.04c	NA
South Korea	2 (0.6)	0.0	NA	7 (2.0)	0.01	NA
China	10 (3.1)	0.0	0.8	5 (1.4)	0.0	0.1
New Zealand	0	NA	NA	4 (1.1)	0.09c	6.3c
India	0	NA	NA	2 (0.5)	0.0	NA
Taiwan	3 (0.9)	0.01	1.0	1 (0.2)	0.0	0.2
Hong Kong	2 (0.6)	0.03c	NA	NA	NA	NA
Philippines	1 (0.3)	0.0	NA	NA	NA	NA
Singapore	6 (1.8)	0.14c	13.1c	NA	NA	NA
Middle East and Africa
Egypt	0	NA	NA	1 (0.2)	0.0	NA
Iran	0	NA	NA	1 (0.2)	0.0	NA
Malawi	0	NA	NA	1 (0.2)	0.0	NA
Pakistan	0	NA	NA	1 (0.2)	0.0	NA
Saudi Arabia	0	NA	NA	1 (0.2)	0.0	NA
South Africa	1 (0.3)	0.0	1.8	1 (0.2)	0.0	0.7
Turkey	2 (0.6)	0.0	7.5	1 (0.2)	0.0	0.3

Abbreviations: NA, not available; RCTs, randomized clinical trials; R&D, research and development; USD, US dollars.

^aData from DeAngelis et al.

^bData from the Organisation for Economic Co-operation and Development.

^cExceeds observed values for the United States.

Discussion

Randomized clinical trials require substantial financial and organizational investment. Historically, the United States excelled in its capacity and influence in surgery. Although it remains the world leader in overall number of surgical RCTs published, it has stagnated and is now behind most of Western Europe in per capita publications. Of concern, especially in the United States, is a global trend toward a decreased number of surgery RCTs per government R&D investment. Influencers of this trend could include the diminished allocation of research dollars to surgery or the inefficiencies in translating funding into publications. The inefficiency of surgical RCTs is a concern; a third of RCTs remain unpublished, and 20% of trials are discontinued at 5 years, most commonly owing to insufficient patient recruitment. It was not possible to determine causation in this analysis. Regardless, action and intervention are necessary to ensure continued government funding and to improve the efficiency of RCTs so that they are published.

Published surgical research is essential for improving surgical practice and increasingly must be accomplished in financially constrained environments. As a surgical community, we must critically analyze and improve the use of research investments. The rate of nonpublication and the amount of trial discontinuations due to insufficient patient recruitment highlight a poor functioning system. If the United States wants to regain its preeminence in surgical research, prompt action is necessary to improve dedicated surgical RCT funding and to transform the US surgical research system into one designed for efficiency.