Journal of Evidence-Based Medicine ISSN 1756-5391

The Cuban Public Registry of Clinical Trials: primaryregistry of World Health Organization.Gladys Jimenez, Marıa Amparo Pascual, Martha Fors, Jose Cobas, Ania Torres,Yamile Cachimaille, Julian Rodrıguez and Isabel Lopez

National Coordinating Centre of Clinical Trials, La Habana, Cuba

Keywords

Clinical trial; Clinical trials registry; Trialregistration; Cuban Public Registry of ClinicalTrials; Cuba

Correspondence

Gladys Jimenez Rivero. NationalCoordinating Centre of Clinical Trials. Postaladdress: Calle 200, entre 19 y 21. RepartoAtabey, Playa. CP 11600. La Habana, Cuba.Tel: 537–2179397- ext (108)Email: gladys@cencec.sld.cu

Received 1 June 2011; revised 15 July 2011;accepted for publication 15 July 2011.

doi: 10.1111/j.1756-5391.2011.01140.x

Abstract

Despite the importance of randomized trials for well-informed decisions in healthcare, a large proportion of the results of these trials are not published, especiallywhen they are negative. Publication bias has a negative impact in the treatmentof patients, due to the distorted impression it leads to for new therapies. ClinicalTrial Registries help to overcome this by providing transparency in the process ofconducting research. The World Health Organization takes the position that theregistration of interventional trials is a scientific, ethical and moral responsibility.Taking account of this global movement, the National Coordinating Centre ofClinical Trials and the Cuban Health Network, designed and implemented theCuban Public Registry of Clinical Trials. The Registry was established in June2007 and is intended for public service in Cuban territory, although it is open toregistrants and patients outside Cuba. The Registry staff developed a strategy tobecome a Primary Registry of the World Health Organization, and this was achievedin February 2011.

Clinical trials registration: a briefoverviewClinical trials registries emerged as a reply within the sci-entific community to various issues about the manipulationof information and scandals related to clinical research, aswell as the tendency of some publishers of medical journalsto report the results of clinical trials in a selective manner(1, 2).

Some of the most important actions in this movement havebeen taken by the International Committee of Medical Jour-nal Editors (ICMJE) and by the World Health Organization(WHO). In August 2004, the ICMJE published an editorialpromoting the use of clinical trials registries. The editorialestablished that, from July 1 2005, the registration of a clini-cal trial in publicly accessible register before the recruitmentof the first patient would be a mandatory requirement for thepublication of the results of the study in one of the memberjournals (3).

In May 2005, the World Health Assembly endorsed thisstand with a resolution (WHA 58.34) that led to the estab-lishment of the International Clinical Trials Registry Platform

(ICTRP) of the World Health Organization (WHO) (4). Thework of the ICTRP is focused on the establishment of two keyelements: the international network of registries (the ICTRPRegistry Network) and a single point of access (the ICTRPClinical Trials Search Portal (CTSP)) to these registries. Thisguarantees access to the information and its availability in astandard format, using a minimum dataset of 20 items (5).The CTSP was launched in May 2007 with records fromthree clinical trial registries: the Australian New ZealandClinical Trials Registry, ClinicalTrials.gov and the ISRCTNRegistry (4). By May 2011, there were 13 data provider reg-istries, including the Cuban Public Registry of Clinical Trialsdescribed in this article (http://apps.who.int/trialsearch/).

Both initiatives, ICMJE and WHO, are independent pro-cesses, but they are closed and related with no contradic-tions between them. The ICMJE formally recognizes theregistries validated by it, and accepts the registries declaredby the ICTRP as “primary registries” (6). The ICTRP es-tablishes requirements for declare primary registry refers toContent, Quality and Validity, Accessibility, UnambiguousIdentification, Technical Capacity; and Administration andGovernance (7).

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Clinical research in Cuba

The development of Cuba’s biotechnology and medical-pharmaceutical products since the 1980s is well known (8).These products have required clinical trials prior to approvaland marketing, both in Cuba and abroad. Within this infras-tructure, the National Coordinating Centre of Clinical Trials(CENCEC, its Spanish acronym) emerged at the end of 1991as a national scientific-technical unit and part of a coordi-nated national network. Its objectives are to design and con-duct clinical trials with rigorous adherence to good clinicalpractices. CENCEC and its Network constitute a compre-hensive organization across the country, which differs fromother similar institutions in the world in a number of ways.Some of CENCEC’s distinguishing characteristics includeits national scope, its combination of scientific services withacademic and health research, and continued human resourcedevelopment in the national health system (9).

The development of new medical products and thereforeclinical research in Cuba is devoted to solving the main healthproblems of the Cuban population. This approach has guidedthe “closed loop” (research + development + production +marketing) of the Cuban biotech industry. In this sense, thebiotech industry benefits the National Public Health Systemwith an important impact on health indicators. The dissemi-nation of these results has been possible because the existenceof the Telematic Network of Health (Infomed).

In 1992, Infomed emerged as the only alternative to copewith the crisis called “Special Period”, which was provokedby the fall of the Socialist bloc and impacted on the en-tire Cuban society, including scientific information in thehealth sector. This alternative used information and commu-nications technologies (10). Infomed ensures connectivityand availability of computers in medical institutions coun-trywide, including coverage at the national, provincial, andmunicipal community levels (11). Moreover, healthcare pro-fessionals can obtain free access to all the Cuban medicaljournals, all books by national authors published by Cuba’sMedical Sciences Editorial (Ecimed, its Spanish acronym),and a good number of international databases, such as HI-NARI, EBSCO, and similar open access resources throughthe Infomed portal (www.sld.cu) (12).

Developing the Cuban registry

In November 2004, the III International Workshop of De-sign and Conducting of Clinical Trials was organized byCENCEC, and Pedro Urra (Director of the National Medi-cal Sciences Information Center & Infomed until 2010 andDirector of Latin American and Caribbean Centre on HealthSciences Information (BIREME) since 2011) gave the lec-ture “Publications policy of Clinical trials: State of the artand position of Cuba”. In this lecture, he mentioned the first

steps for trials registration and the importance for Cuba andCuban journals to follow this policy.

Two years later, at the end of 2006, CENCEC and Infomed,both governmental and not-for-profit organisations subordi-nated to the Ministry of Public Health (MINSAP, its Spanishacronym), began to develop the Cuban Public Registry ofClinical Trials (RPCEC its Spanish acronym). This was pos-sible because of the experience of both institutions in theirrespective fields and the willingness to work together as ateam.

The site of the RPCEC was launched in June 2007(http://registroclinico.sld.cu). This site allows Cuban spon-sors (registrants) to register their clinical trials. The main goalof the registry is to provide a complete, up-to-date overviewof clinical trials conducted in Cuba, although it is also open tosponsors and patients outside Cuba (13). The development ofthe registry took into account the requirements of the ICTRP(7), but trial registration was only in Spanish. This allowedthe main sponsors of clinical trials, working for the biotech-nology industry, to register the majority of their ongoingclinical trials. Thus, during its first year the registry workedonly in Spanish and registered 70 trials. However, to becomea primary registry of the ICTRP, it was necessary to developan English website that included English forms and to im-prove some processes and activities related to connectivityand working procedures.

Strategy for becoming a Primaryregistry: barriers and challenges

During the first semester of 2008, staff of the registry devel-oped the English form and translated the Spanish pages of thesite in order to have a complete site in English, and not onlythe trial form. The trial form contained the 20 WHO TrialRegistration Data Set items and a set of variables consideredby the RPCEC (including, for example, the approval by Reg-ulatory agency and the approval by Ethics Committees). Thevariables were grouped in sections to facilitate identificationby the registrants and to make data collection easier. Thesubmission of both forms, in Spanish and English, to registera new clinical trial became mandatory in August 2008.

The registry established a communication system for reg-istrants with timetables for the progressive translation of thefirst 70 trials. The registry made two contacts with the spon-sors: the first established a chronogram in terms of peri-ods and the second established the chronogram accordingto the trials registered by each registrant. If they had ac-complished these tasks within the proposed schedule, thetranslation would have been finished by the end of 2008.However, not the registrants were able to translate all thetrials. Therefore, in April 2009, the registry contracted anofficial Cuban institution engaged in translation services to

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translate the records for all the Spanish trials, but we insistedthat the sponsors also prepared a translation as a controlquality procedure to guarantee the reliability of this informa-tion. After one year, this task had not been completed: only25 trials were registered in English (36%) and the other45 trials were still without translation (64%). Therefore, theAdministrative Officer of the registry contacted the CubanOffice of the Pan American Health Organization (PAHO),which collaborated with the translation of the trials. Thetranslations were sent to the sponsors so that they could enterand review the data, but they failed to fulfil this expectation.

In September 2010, the Administrative Officer of the reg-istry asked the ICTRP for advice on the next steps and de-cided to enter the translations into the database. The staffwas divided into two groups: one group entered the trans-lated data and the other group reviewed the entered data tocheck the accuracy of the translation. Finally, the Adminis-trative Officer registered the trials. This activity followed atraining programme and was done using specific instructions.The work was finished in December 2010.

Another requirement for becoming a primary registry wasthe need for the website to be available 24 hours a day,seven days a week (24×7). The staff of the registry organizedmeetings with the group in Infomed that was responsible forthe maintenance of the servers, and the website administratorof the RPCEC implemented daily monitoring to eliminatetransient unavailability of the site due to technical problems.

Across the four years from 2007, the ICTRP itself hadalso evolved to high levels of quality and has increased itsrequirements. For this, the RPCEC needed to improve someprocesses or activities such as the reviewing process beforea trial could be registered, the quality of the data and thedevelopment of Standard Operating Procedures (SOPs) forits main activities.

The staff of the registry created an “Evaluation form”to assess the entry for each trial. It included the items inthe Spanish and English forms which need to be checked.The “Evaluation form” followed the scheme of data in theregister forms. Every item contained the same help messagethat appears in “Data Definitions. Clinical Trials Forms”(http://registroclinico.sld.cu/rpcec_definiciones.pdf), anddetails of the information that must be checked. Theevaluation led to one of three steps: “To register the trial”,“Reject the trial”, or “Modify the trial and register”. If theresult of the evaluation is “register” or “modify”, both formsreceived the same code. If the outcome was “Reject a trial”,a new reviewing process by the registrant was mandatory(so that the registry could obtain complete and meaningfuldata). In all cases, the RPCEC sent an email to registrantswith the outcome of the evaluation process and some usefulcomments.

The SOPs covered the principal activities, which at thebeginning of the RPCEC functioning were shown as flow

diagrams or instructions. These included the creation of aresponsible registrant account in RPCEC, the process to reg-ister or update a trial, the updating of the website and creatinga backup.

From the beginning of the registry, its disseminationthroughout the country was one of the key tasks. In 2008,the registry organized a workshop with the main biotech-nology centres sponsors of clinical trials. In January 2009,the registry was presented in the meeting of Scientific Polein Havana that involves over 40 research institutions and,three months later, it was presented in a National Method-ological Seminar organized by the Science and Technologydivision of MINSAP. In December 2010, the registry waspresented in a plenary lecture during the congress “Phar-macology Havana 2010”. Most recently, in March 2011,the registry was presented in the workshop of the coor-dination network of CENCEC. In all cases, the lecturesshowed an overview of clinical trial registration, the char-acteristics of the process and the Cuban registry. Infomedhas given wide coverage to the registry, which is availablefrom its homepage as an essential link. It has also announcedevents to the registry, including the launch in 2007 and thenotice about the designation of primary registry status in2011.

As the result of the strategies described in this article,the RPCEC achieved the condition of Primary Registry inFebruary 2011, and was incorporated to the ICTRP. Theformal announcement of the registry was in April 2011 andthe RPCEC has sent its data on trials to the ICTRP sincethen. In July 2011, it includes 120 trials and 118 of these areavailable in the ICTRP.

Next steps. The future

The principal activities of the RPCEC are focused on theimprovement of information technology support and on thedesign and implementation of a training program for regis-trants. The first of these will improve the interface betweenusers and the database with a focus on two types of users: theexternal user and the staff who administer the website. Thesecond activity will increase knowledge about clinical trialregistration and the Cuban registry. Parallel to this, the reg-istry is working with the Cuban regulatory agency to developmechanisms to enforce trial registration before the recruit-ment of the first patient. This is the most effective way toestablish the mechanisms to guarantee compliance (4), inthis case at a national level.

The RPCEC is able to collaborate with other countries inthe region who are working to establish their own registriesor who wish to register their trials. The registry will develop astrategy to increase the international visibility of the RPCECto make this possible.

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As a WHO primary registry, the RPCEC will take all theactions necessary to contribute continually to the interna-tional registries’ network and to improve itself.

Conclusions

Over the recent years, the strategy for the Cuban PublicRegistry of Clinical Trials allowed it to fulfil the require-ments established by the ICTRP of WHO to become a pri-mary registry. This was achieved in February 2011, allowingRPCEC to be incorporated into the international platform.Since April, the RPCEC has been a data provider to, WHOwith the consequent advantages related to the publication ofthe results in national and international Journals. This accep-tance also provides better reliability for the Cuban pharma-ceutical industry and biotech research centres and increasesthe integrity and transparency of the Cuban Health Systemand Medical sciences of the country.

Acknowledgements

We thank Pedro Urra for his support and his spirits. We alsothank him for being the first to introduce us to the processof clinical trials registration in Cuba. We thank Infomed forits technical support, in particular to the engineer HaddidVega who has collaborated very closely with the developmentand maintenance of the registry website. We thank PAHO inHavana for its collaboration with the translation of the trialrecords and for other activities, such as the participation of theregistry in the meeting of 2010 and the announcement of theregistry. We thank to the International Clinical Trials RegistryPlatform, in particular Davina Ghersi, Maribel Gomez andGhassan Karam, for their help in all the stages of our journeyto become in primary registry of WHO.

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