A total of 3496 and 1427 registrations were found in the four CTRs involving Czech Republic and Portuguese institutions, respectively: ClinicalTrials.gov, EU-CTR, ISRCTN, and ANZCTR. Clinical trials were screened to isolate those with a non-commercial sponsor, recruiting sites in Czech Republic or Portugal, and a start date between 01/01/2004 and 31/12/2017.
Identification of non-commercial studies
The number of trials identified in each database is shown in Figure 1. After discarding industry-sponsored trials, non-interventional studies, or those with no recruiting sites in Czech Republic or Portugal, 485 and 378 non-commercial trials (i.e. IICTs) were respectively considered eligible from all the screened databases. The same trial registered in different CTRs was separated and considered as duplicate. After discarding duplicates, a total number number of 439 IICTs were identified involving Czech Republic whereas for Portugal 328 trials were found. Forty-one percent and 49% of the studies were already completed and from those 41% and 58% were published, in Czech Republic and Portugal, respectively.
Characteristics of IICTs in Czech Republic and in Portugal
In both countries, most of IICTs has a national sponsor and were performed in the respective country (Figure 2A) with a low percentage of multinational trials (implemented in other countries) – 6% in Czech Republic (n=15/242) and 4% in Portugal (n=8/185). Both countries have also the same percentage of trials with international sponsors (41%) (Figure 2A). In Czech Republic, most trials´ sponsors (42%; n=183/439) were hospitals while in Portugal, universities assume the sponsorship in higher number of trials when compared to the other types of organizations (47%; n=153/328) (Figure 2B).
IICTs in both countries are mainly funded by public organizations (Figure 2D) such as universities, hospitals, disease specific organizations, foundations and funding agencies: 78% (n=343/439) in Czech Republic and 69% (n=226/328) in Portugal. Considering all types of interventions funded by public organizations, 50% (n=173/343) are trials with IMPs in Czech Republic and only 27% (n=60/226) in Portugal. In the latter, most trials funded by public organizations, 36% (n=82/226), are behavior-based (Figure 2 D, 2E). Details about each registry are provided as Supplementary Information 2 (S.I.2).
Clinical trials funded by national and international funding agencies
One of the great public funders of the IICTs in both countries were funding agencies (national and international) corresponding to 29% (n=109/381) in Czech Republic and 21% (n=60/282) in Portugal of the public funding. The total number of trials indicated above (381 and 282) refers to those funded by public organizations alone or together with private institutions (Figure 2D: Public and Both). From the 109 IICTS trials funded by governmental agencies in Czech Republic 65 % (n=71) of the trials were funded by national funding grant agencies while the remaining 35 % (n=38) IICTs were funded by international counterparts (Figure 3A). Figure 3A shows that both national and international agencies mainly fund trials with IMPs. Among the 61 trials funded by the Czech Health Research Council (Table 1), 32 (52%) are testing medicinal products (data not shown).
On the other hand, among the 60 IICTs in Portugal receiving financial support from funding grant agencies, only half of these (n=30/60) were funded by national funding grant agencies or funding programs (Figure 3B) while the other half was funded by international funding agencies. Among the 27 trials funded by Fundação para a Ciência e Tecnologia (Table 1) only one (4%) is testing medicinal products (data not shown).
Table 1 – National and International funding agencies and programs in Czech Republic in and Portugal and respective number of funded trials. (Nº=number of clinical trials funded by the respective funding organization/program)
Czech Republic
|
|
Nº of Trials
|
National Funding Agencies / Funding Programs
|
|
Internal Grant Agency of the Czech Ministry of Health (IGA until 2014)
Currently AZV (Czech Health Research Council)
|
61
|
Charles University Research Fund
|
10
|
International Funding Agencies
|
|
European Commission (includes H2020 and Erasmus Program)
|
18
|
Canadian Institutes of Health Research (Canada)
|
7
|
European Regional Development Fund
|
6
|
Medical Research Council (UK)
|
7
|
Portugal
|
National Funding Agency/ Funding Programs
|
|
Nº of trials
|
Fundação para a Ciência e Tecnologia (FCT)
|
27
|
National Structural funding (COMPETE, PRODEP)
|
2
|
ARDITI – Agência Regional para o Desenvolvimento da Investigação
|
1
|
International Funding Agencies
|
European Commission (includes H2020 and IMI Programs)
|
17
|
Australian National Health Service and Medical Research Council
|
5
|
National Institutes of Health (NIH, USA)
|
3
|
British Medical Research Council (UK)
|
2
|
EEA Grants
|
1
|
Carlos III Institute of Health (Spain)
|
2
|
The level of participation of these two countries in international grants was similar (n=38 and n=30, respectively), most of these involving trials with IMPs in both cases (Figure 3A, 3B).
The organizations receiving national funds, thus acting as sponsor, in higher number of trials in Czech Republic were hospitals (32%: n=35/109) and universities (22%: n=24/109). Whereas in Portugal were the universities (40 %: n=24/60) that sponsored more trials funded by national funding agencies followed by hospitals (7 %: n=4/60). Portuguese hospitals sponsored more trials funded by international funding grants then with national funding grant agencies (n=8 vs n=4).
Table 1 shows all the funding grant agencies identified both in the registries and in the publications for each completed and published clinical trial. In Czech Republic there were a higher number of trials funded by national funding agencies and the number of registrations is gradually growing every year since 2004 (S.I.1, Fig. 1 D,E). When compared to Czech Republic, a lower number of funded IICTs by public funding agencies were identified in Portugal, however, the national investigators have been involved in trials with more diverse funding opportunities, especially international ones.
National policies for clinical research
Both countries present national public policies implemented (or not) for clinical research, in particularly IICTs, which are summarized in Table 2. The data were collected from national legal decisions, analysis of the call’s eligibility criteria for funding national infrastructures and projects as well as higher education institutions in each country.
There have been legal decisions to establish clinical research as a priority that included the membership of ECRIN-ERIC and the definition of the clinical investigator status in both countries [7-13]. The Internal Grant Agency (IGA) of the Ministry of Health supporting medical research and development was established in 1990 in Czech Republic and has been replaced by Czech health research council, AZV, founded on 01/04/2014 [17,18]. This council, launch calls each year and supports the selected applications of clinical research in the different medicine areas. The establishing the AZV and defining the national priorities of oriented research, experimental development and innovations are the long-term strategies of the Czech government to support the clinical research in medicine. Nevertheless, to our best knowledge in Czech Republic, the higher education courses specific to train clinical trials professionals are being prepared. In Portugal, the national government supported and invested in specific training for medical doctors14 and research team professionals from hospitals [14].
Table 2 – National public policies implemented by the Portuguese and Czech governments to promote clinical research.
Public Policies
|
Czech Republic
|
Portugal
|
Establish clinical research as a priority
|
Yes [7]
|
Yes [8,9,10]
|
Be member of ECRIN-ERIC
|
Yes [11]
|
Yes [12]
|
Define a legal specific status for clinical investigators
|
Yes [13]
|
Yes [8]
|
Invest in public infrastructures to promote/support IICTs
|
Yes
|
No
|
Specific and periodic funding for IICT
|
Yes
|
No
|
National funding agency specific for health research
|
Yes
|
No*
|
National public initiatives for clinical research team’s capacitation
|
No**
|
Yes [14,15]
|
ECRIN- ERIC: European Clinical Research Infrastructure Network - European Research Infrastructure Consortium
*A national agency (AICIB) for clinical research funding is now being implemented in Portugal [16];
** A course dedicated to clinical trials management is under preparation
Clinical trials published in peer-reviewed scientific journals
In Czech Republic, there are 41% of published trials among the 180 completed while in Portugal, from the 144 completed trials, 55% are published in peer-reviewed journals (Figure 1, step 7). In Czech Republic, a higher percentage of published studies focus on IMPs (44%, n=32/73), followed by surgery and procedures (32%). On the other hand, in Portugal, most publications focus on behavior studies (37%, n=29/79) followed by IMPs (32%) (Figure 4 A).
The impact factor (IF) of the journal where these IICTs were published varies widely between 0 to 72. Thirty percent (30%, n=23/73) of the trials performed in Czech Republic with publications were published in journals with IF between 6 to 20. Around 75% (n=59/79) of published papers with trials involving Portuguese organizations, have an IF below 5 and only 16% (n=13/79) were published in journals with IF above 20. The average IF of all these journals is similar for both countries and is around 9. Portuguese investigators are authors/ co-authors of 15% of the papers published in journals with IF>20, conversely to what is observed with Czech investigators who authored/co-authored of 86% of the papers published in high impact factor journals (Inset B1, Figure 4B). Furthermore, international funding agencies funded 71 % of trials in Czech Republic and only 31% in Portugal that were published in journals with IF>21 (Inset B1, Figure 4B). None of these published trials in high impact journals was funded by the Portuguese national funding agency while in Czech Republic, one of these trials was funded by the national funding agency. Around half of the trials published in journals with IF>21 are funded by private funders (43% for Czech Republic and 54% for Portugal). Additionally, most of these published trials were multinational and focused in IMPs, in both countries.