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Gross Domestic Product (GDP) and productivity of schizophrenia trials: an ecological study

  • Carina Moll1,
  • Ursula Gessler1,
  • Stephanie Bartsch1,
  • Hany George El-sayeh2,
  • Mark Fenton2 and
  • Clive Elliott Adams2Email author
BMC Psychiatry20033:18

DOI: 10.1186/1471-244X-3-18

Received: 16 September 2003

Accepted: 05 December 2003

Published: 05 December 2003

Abstract

Background

The 5000 randomised controlled trials (RCTs) in the Cochrane Schizophrenia Group's database affords an opportunity to research for variables related to the differences between nations of their output of schizophrenia trials.

Methods

Ecological study – investigating the relationship between four economic/demographic variables and number of schizophrenia RCTs per country. The variable with closest correlation was used to predict the expected number of studies.

Results

GDP closely correlated with schizophrenia trial output, with 76% of the total variation about the Y explained by the regression line (r = 0.87, 95% CI 0.79 to 0.92, r2 = 0.76). Many countries have a strong tradition of schizophrenia trials, exceeding their predicted output. All nations with no identified trial output had GDPs that predicted zero trial activity. Several nations with relatively small GDPs are, nevertheless, highly productive of trials. Some wealthy countries seem either not to have produced the expected number of randomised trials or not to have disseminated them to the English-speaking world.

Conclusions

This hypothesis-generating study could not investigate causal relationships, but suggests, that for those seeking all relevant studies, expending effort searching the scientific literature of Germany, Italy, France, Brazil and Japan may be a good investment.

Background

Most randomised trials are produced in the USA. Certainly, when it comes to trials relevant to the care of people with schizophrenia, certain countries have a strong tradition of trialling, and others have not [1]. This study investigates whether certain accessible economic and/or demographic variables are, in some way linked, and can be predictive of productivity of schizophrenia trials.

Methods

The Cochrane Schizophrenia Group has constructed a unique collection of reports of randomised controlled trials relevant to schizophrenia [2]. In this collection a single electronic record is made per study and the multiple references/reports/presentations of that study are appended to that single record. This attempt to decrease the confusion caused by 'salami' publication is made possible using custom made specialised reference/study management software [3]. A study-based register affords an opportunity for research. Each study record in the Cochrane Schizophrenia Group's database has been coded for 'country of origin'. This has had to be defined as the country from which the first author originates. These data were extracted from the database (currently 5062 studies), and the number of trials undertaken in each country calculated.

Data for gross domestic product (GDP), population, GDP/Capita, and the number of telephones/100 people, for all countries, were acquired from the United Nations website [4]. A second website was used to supplement the first dataset where gaps were apparent [5]. Both datasets were figures from 1997. These particular sets of data were chosen as they are widely accessible, and because the authors felt they each add some qualities worthy of consideration. GDP is a measure of the sheer wealth of a nation. The population is the number of people, and, with a lifetime prevalence of 1% for schizophrenia, it represents the numbers of people with the illness who live in the country. GDP/capita is a measure of potential individual affluence, and number of telephones/100 people, is a crude estimate of technical development.

Statistical analysis was performed using StatsDirect, Statistical Software [6]. Number of randomised controlled trials relevant to schizophrenia was correlated against each of the four economic/demographic variables using simple and linear regression and Pearson's correlation calculated (Appendix 1 [see Additional file 1]). Finally, the best-fit plot was used to interpolate X (economic/demographic variable of best fit) to Y (calculated number of trials). In this way it was hoped to estimate the expected output of schizophrenia trials and compare this to the actual output.

Results

Of the 5062 studies, 61 (1.21%) were reported in such a way as to make reliable data extraction of country of origin impossible. Data extraction for 'country of origin' defined in the way used in this study has been found to be reliable in this sample with over 90% agreement [6]. Simple frequencies of studies by country verify that the USA is the most productive country of schizophrenia trials (Table 1).
Table 1

Top 10 producers of schizophrenia trials

Country

Simple frequency of trials (n)

USA

2363

United Kingdom

669

Canada

275

Germany

256

Japan

113

France

108

Netherlands

104

Sweden

101

Italy

91

China

87

TOTAL

4167

Correlation of the number of trials by each of the four variables is shown in Table 2.
Table 2

Correlation of number of trials (if >0) vs each variable

Variable

r

95% CI for r

r2

GDP (in million US $)

0.87

0.79 to 0.92

0.76

Population (in thousands)

0.14

-0.11 to 0.38

0.02

GDP/Capita (US $)

0.31

0.06 to 0.52

0.10

Telephones/per 100 inhabitants

0.30

0.06 to 0.52

0.09

The correlation with GDP was by far the best fit with 76% of the total variation about the Y explained by the regression line (log transformation made little difference to the analysis). Having created the best-fit line, GDP data from every country, whether or not they had been found to produce a relevant randomised trial, were interpolated to estimate the number of trials predicted by GDP.

The results of these interpolations fell into three distinct groups: i. Countries for which we had failed to identify any schizophrenia randomised trials; ii. Countries which had produced schizophrenia trials and which had a GDP that predicted trial activity; and finally, iii. Countries for which the GDPs predicted no trial activity, but that had undertaken a number of relevant studies.

Countries with no schizophrenia trials

We could not identify any randomised controlled trial research for people with schizophrenia for 132 (out of 192) countries. All of these countries, with the exception of Indonesia and Iraq had such low GDPs that trial activity would not be expected. Indonesia's GDP of $214593 million/year suggests that 25 studies could be expected, but wide confidence intervals do not exclude zero productivity (95% CI -16 to 66). The same applied for Iraq's $149036 million/year, with nine trials predicted but similarly wide confidence intervals (95% CI -32 to 51).

Countries productive of schizophrenia trials and also with a GDP that predicted trial activity (Table 3)

Table 3

Countries productive of schizophrenia trials ordered by level of productivity

country

GDP (mUS $)

actual trials > 100

predicted trials

% predicted output (95% confidence intervals)

Finland

119834

38

2

1900 (1312–2488)

South Africa

129094

26

5

520 (340–700)

Denmark

161455

79

12

658 (525–792)

Canada

607702

275

118

233 (212–254)

Norway

153362

24

10

240 (167–313)

Greece

118172

15

2

750 (397–1103)

Switzerland

172400

54

15

360 (278–442)

Sweden

227757

101

28

361 (301–421)

Poland

135623

17

6

283 (175–392)

UK

1283335

669

279

240(226–254)

Netherlands

363342

104

60

173(152–196)

Belgium

242508

49

32

153 (128–178)

Austria

206236

33

23

143 (117–170)

USA

7824008

2363

1831

129 (127–132)

Hong Kong

175200

18

16

113 (95–130)

Australia

402787

64

70

91 (85–98)

India

388649

48

66

73 (60–85)

Germany

2089845

256

470

54 (48–61)

Nigeria

142920

4

8

50 (1–99)

China

901981

87

188

46 (36–57)

Turkey

191865

8

19

42 (8–76)

Thailand

153909

4

10

40 (-8–88)

Italy

1145370

91

246

37 (27–47

France

1394124

108

305

35 (26–44)

Spain

531289

32

100

32 (16–48)

Russian Federation

447103

21

80

26 (7–45)

Mexico

402109

13

69

19 (-2–40)

Iran

159391

2

12

17 (-35–68)

Saudi Arabia

134825

1

6

17 (-56–90)

Republic of Korea

442543

13

79

16 (-4–37)

Brazil

806972

21

166

13 (-2–27)

Argentina

323548

6

51

12 (-14–38)

Japan

4192669

113

969

12 (6–18)

Taiwan

308000

4

47

9 (-19–36)

Finland is far ahead of other nations but numbers of both actual and expected studies are small. Denmark, however, is highly productive, as is Sweden, the UK, Canada and the Netherlands. Using these data, the USA's strong tradition of undertaking and disseminating trials still is outstanding, but it is the 14th most productive country of schizophrenia trials, according to percent of predicted output.

Countries for which GDP predicted no trial activity, but which had undertaken relevant studies

Twenty-five countries fell into this category, five of which produced more than ten studies when none were predicted by GDP (Table 4).
Table 4

Countries with GDPs that predicted no studies, but with >10 trials

Country

GDP (million US $)

Trials

Israel

92587

83

Czech Republic

52038

78

New Zealand

65291

14

Yugoslavia (Serbia/Montenegro)

17000

10

Hungary

45725

10

Discussion

Strengths and limitations

There are several limitations of the datasets used for this work. The study-based register is in its first draft. Many papers may be designated as a unique study when they only represent another report of an already identified randomised trial. Being fully confident of having minimised undisclosed multiple publications would take some time. This limitation will result in an overestimate of the number of studies. The overestimate probably is greatest for English language reports of industry-sponsored trials, the great majority of which originate from the USA. A second limitation is that the studies are from 1950 to the present day but the economic/demographic data are from 1997, disregarding the economic/demographic/political changes over time.

Economies that developed rapidly after World War II, such as China, Germany, Italy, Japan, Korea and Taiwan are being judged by the GDP of 1997. This technique could overestimate the expected output of trials from countries in which average GDP, or GDP relative to other countries, would have been considerably less than that of 1997. The crude definition of country of origin as country from which the first author originates is also a limitation. The author's origin may not represent the country where the study took place and we do not know the proportion of studies for which this accurately reflects where the work was undertaken. Lastly, the use of GDP is potentially a surrogate measure of one or many causal relationships. It could be a surrogate for the national investment of the pharmaceutical industry, the funding and activity of universities, or/and the degree to which fragmentation of the family had lead to public concern about the care of people with schizophrenia. As with any correlation study, this work is solely hypothesis-generating and not testing.

The USA produces more schizophrenia trials than any other country (Table 1). When the correlation of the four economic-demographic variables was undertaken GDP, whether logged or not, correlated highly with trial output (whether logged or not). Other variables did not (Table 2). This suggests that trial productivity may neither be a function of national burden of ill people, nor of individual prosperity, and not of technological development. Trial productivity seems more linked with the affluence of the country, irrespective of population, or technological development.

Every country that had not produced any randomised trials relevant to schizophrenia had a current GDP that predicted a study output of zero. The two exceptions (Indonesia and Iraq) had larger GDPs, but interpolation of which into the plot still predicted a study output compatible with zero (see 95% CIs). Every nation that can afford it, and many that cannot, undertake schizophrenia trials.

Table 3, highlights countries with what may be strong traditions of undertaking and disseminating trials, well beyond that predicted by GDP. On the other hand, the plot suggests that Japan, France, Italy, China and Germany are conducting only between 10–50% of trials predicted by their high GDPs. One reason for these poor results may be that those compiling the Cochrane Schizophrenia Group's database are not identifying relevant trials from non-Anglophone sources. These figures would suggest that those seeking as yet unidentified studies should focus efforts on these countries, where searching is likely to be fruitful. Investing effort in finding studies from Thailand, however, where only an additional six studies are predicted to have not yet been identified, may be considerable effort for little reward. Certainly, researchers in Japan are acutely aware of the problem of disseminating their work [7] and have recently created accessible registers to combat this [8]. The under-representation of schizophrenia trials from certain countries could also mean that the studies do not exist and that the tradition of evaluation of care for this client group is not strong in these states.

Twenty-five countries have a GDP that predicts no schizophrenia trial activity yet some is apparent. Table 4 shows those states where more than ten studies have been identified. Israel is out ahead, but with the Czech Republic, where GDP may be a more accurate representation of the state's affluence, a close second.

Conclusions

In summary, this hypothesis-generating study finds close correlation between current GDP figures and a country's production of schizophrenia trials. It suggests that some states have been remarkably generous in their commitment to evaluation of care of this group of people. For other wealthy countries, however, there is a suggestion that either substantial numbers of randomised trials remain unidentified, or that there is no great interest in randomised trials relevant to people with schizophrenia

Declarations

Acknowledgements

The authors would like to thank Professor Toshiaki Furukawa, Chair, Department of Psychiatry, Nagoya City University Medical School, Japan for his helpful comments on the manuscript.

Authors’ Affiliations

(1)
Schule fuer Medizinische Dokumentation, Universitaetklinikum Ulm, Academie fuer Medizinische Berufe
(2)
Cochrane Schizophrenia Group Academic Unit of Psychiatry and Behavioural Sciences University of Leeds 15 Hyde Terrace

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Copyright

© Moll et al; licensee BioMed Central Ltd. 2003

This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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