The current state of clinical trials in Portugal

January 26, 2013 | By Márcio Barra

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As a first year student in pharmaceutical medicine in Portugal, I’m very interested on how does my country behaves when it comes to clinical trials, especially since in a few months I will be giving, hopefully, my first steps in the world of drug clinical research. As my readers surely know, Portugal (and the rest of Europe) is going through a very rough economic crisis, with recession hitting all sectors of the economy and budget cuts left and right. It’s a very daunting prospect for first jobs, as unemployment just hit a record high of 16% here in Portugal.

So, my interest on how my field of training fares in Portugal is non-surprising. I have previously published two reports which provided some raw numbers on clinical trials in Portugal for the last few years, (link 1 and link 2), but they don’t explain what’s behind those numbers, and a lot of questions occur when looking:

  • Why is the number of clinical trials submitted for approval in Portugal decreasing?
  • Why is it that, year after year for the last couple of years, we have less and less clinical trials conducted in our hospital centers?
  • Why do we have so few Phase I clinical trials?
  • How does Portugal stand against other EU member states?
  • What is the reason for these numbers? Is it the hospitals? Lack of patients? Sponsors? The regulatory authority?
  • What can be done to change this trend?

As previously stated in the two reports, the number of clinical trials submitted for approval in Portugal is decreasing, with 76 trials approved in 2012. Placed against other EU countries, these numbers are very poor.

In a survey conducted by APIFARMA in 2009 to ten pharmaceutical companies who conduct a big slice of the clinical trials in Portugal, the number of active clinical trial in Portugal was lower than Austria, Belgium and the Czech Republic (countries with similar number of inhabitants).

Country

Number of active clinical trials

Number of planned sites

Planned patient recruitment

Investment (in millions of euros)

Portugal

147

461

3.917

58,755

Austria

188

596

5.602

97,530

Belgium

328

1.024

12.996

194,940

Czech Republic

218

967

15.433

231,495

With the lower number of trial comes lower investment from sponsors. Portugal, compared to Belgium, lost 136 million of euros in potential investments.

Another study from APIFARMA, this one still in progress, presents some preliminary data collected from 443 clinical trials conducted in 2007 to 2011, which shows light on how much money was planned to be invested in Portugal versus the money that was actually invested. The still preliminary data shows that 14 million euros were lost in that period, mostly from unsatisfactory patient recruitment.

Looking at these numbers, one wonders how a pharmaceutical company chooses where to conduct a trial? They usually look for the following factors:

  • The presence of expert investigators and opinion leaders, who can carry a trial forward and help promote the knowledge produced in a trial.
  • The market share of the country, its economic dimension, if the country is a significant player in the international economy and if he has a market that can afford the medication after approval.
  • Quality of the execution of the trial versus the cost. Pharma companies place a lot of importance on if the country has the appropriate facilities and procedures to recruit patients.  Usually, the less bureaucracy and legal hurdles a country has, the better he is at recruiting. Good approval times by the regulatory authorities and ethic committees are also a big plus.

Sucess stories

Belgium, a country with similar dimensions to Portugal, is a case of success in Europe in the field of clinical trials. It has a strong presence of initial phase exploratory clinical trials and a good number of phase III trials. Their approval times for clinical trials are extremely competitive, averaging 15 days for exploratory and 28 days for confirmatory studies (not counting clock-stop periods). Sponsors choose Belgium as a CT location because of the quality of the data produced, access to the CT sites, the mentioned approval time and the expertise of the healthcare professionals. Cost is a big hurdle in Belgium though, alongside patient recruitment rates, but major Belgium stakeholders have set up initiatives to counter these limitations.

Poland, another case of success in the European Union, is ranked 10th in the world and 1st among emerging (and CEE) markets in the number of total clinical trials, with 1,176 clinical trial sites (2008 data). In 2010 they saw 469 new clinical trial applications.  The market structure of Poland is a bit different than the rest of the world, with CROs operating the majority (70% by volume, 53% by value) of trials. What is behind this success?

  • The population size (38 million)
  • Efficient patient recruitment
  • Quality of the execution, data produced, and of the medical staff
  • Number of CRA’s assigned to each clinical trial

The efficient patient recruitment is due to the population size and the incentives provided to the patient, as better healthcare service is provided to them under a clinical trial compared to standard healthcare. Contrary to Belgium, they lack in efficient approval times for clinical trials.

Looking at the wider picture, of the 4000-5000 new clinical trials approved in the EU, Portugal has a small slice of the cake, usually 100 new trials each year. Almost all of the trials conducted in Portugal are multinational trials; few are exclusive to our territory. In other EU countries, there are a bigger number of national clinical trials. This can be justified by the low number of academia sponsored trials in Portugal (only 2% of the applications in 2012 ). As academia sponsored trials are usually smaller scale studies, the clinical trial activity in Portugal is mostly focused on phase III trials. Competition is tightening up at the moment for Europe though, with emerging economies, like the BRIC countries, providing fast patient recruitment rates and less bureaucratic red tape to companies.

Impact of clinical research

The lack of interest from sponsors to conduct clinical trials in Portugal is harmful to the country and its economy. The direct (and indirect) impacts of clinical trials in a country’s economy are very significant:

  • They contribute to the budget of a state, through paid taxes.
  • Provide alternative cost savings.
  • An additional mechanism of remuneration to investigators.
  • Employment opportunities, additional work for researchers and young physicians and economic stimuli for other supporting business.
  • Improved access for patients to better treatments; usually sponsors provide more intense care and therapy for a clinical trial patient than what a normal patient gets under the standard healthcare system. Sometimes patients can’t even afford the drug when it’s released in the market, but volunteering in a clinical trial can make it accessible.
  • Knowledge sharing and transfer of new technologies. Potential spillover effect to other areas of healthcare.

Portugal could certainly find these contributions useful in the current economic circumstances. Efforts should be done to motivate pharmaceutical sponsors to invest in Portugal and conduct clinical trials here. GSK, Lilly, and recently Pfizer closed their clinical research units in Portugal, which shows that big sponsors are simply not interest in investing in Portugal.

Portugal’s flaws

From my experiences talking with some members of the Portuguese clinical trial industry and reading interviews and reports, the low focus of sponsors to conduct trials in Portugal can be explained by a series of issues:

  • The financial contract is the first big one in Portugal. This document states the financial terms of the trial and other details, and is signed between the sponsor of the trial and the concerned sites. Moreover, it has to be approved by the national ethics committee before coming into full force. While the national legislation states that financial compensation to the investigators must be detailed in the financial contract, few hospitals in Portugal actually pay their physicians for conducting and being involved in clinical research. Thus, there is very little incentive for many physicians and other healthcare professionals to be actively involved in clinical research. Motivation is extremely important for conducting any job, and investigators should be rewarded for their effort when working in a trial.
  • The lack of a standard model for financial contracts delays negotiations between sponsors and clinical trial sites.A standard model for financial contracts, accepted and approved by all Portuguese clinical trial stakeholders would surely be helpful in reducing bureaucracy.
  • The need of approval from several ethic committees is another hurdle. In Portugal, the ruling ethic committee is the CEIC, and a study to be legal has to be approved by it. However, all public and private health institutions have what is called a CES, a local ethic committee.  What usually happens is that, while the CEIC has a 60 day period to give their evaluation, the clinical trial sites do not approve the trial without the favorable opinion of their own ethic committee, creating a kind of double ethical evaluation, delaying the trial start. Worse yet, there is no standard procedure on how the different CES conduct their evaluation. One CES may do one thing, and other CES may do something completely different.
  • CEIC is not a centralized ethic committee and thus cannot provide a single, national opinion on a clinical trial. Some structural reforms in how the Portuguese ethic committees conduct their operations are certainly needed.
  • Morevoer, Belgium’s clinical trial legislation doesn’t mention that approval from a national commission for data protection (CNPD) is needed, unlike Portugal. The more agents a sponsor needs approval from, the slower a trial starts. Streamlining is definitely in order for Portugal.
  • There are many flaws how on a sponsor requests authorization from the Portuguese national commission for data protection. Their electronic form is outdated in format, not allowing the sponsor to attach a document or annex a file in some sections, while allowing in other sections.
  • As for the low number of phase I and phase II trials, it could be due to cultural reasons and absence of proper facilities.  Before the clinical trial directive standardized the EU clinical trial landscape, the national legislation didn’t allow clinical trials to be conducted in healthy patients. Consequently, Portugal didn’t have a background in exploratory trials, until the creation of the phase I unit by BIAL.
  • Another concern is the almost nonexistence of clinical trials conducted at the initiative of academia and academic researchers. The shortage of funds and incentives to conduct clinical research makes them a tricky proposition to academic researchers. Turning this type of research into a more appealing proposition for them could potentially attract more phase I and phase II trials.
  • But it’s not just phase I trials that need proper facilities. Throughout Portugal, many hospitals are simply ill equipped to manage a clinical trial, usually by lack of a clinical trial management team, experienced physicians in clinical trials and proper standardized procedures for it’s operations. Creating specialty sites could probably help, but it’s probably something currently not on the government agenda.
  • There is also the issue of public perception. The general public and many members of the media don’t understand what a clinical trial is and the value it holds. The idea that patients who join clinical trials are guinea pigs, submitted to numerous risks is very much ingrained in Portugal, and that needs to change. The public needs to understand that a clinical trial is a way for a patient to access an innovative therapy, which may very well extend his life or get rid of a serious symptom. The media should also play a more active part in this. Promotion of clinical trials is hard enough as it is, with all its restrictions in Portugal. Changing the perception of patients would be a great boost to patient recruitment rates.

And last, there is the nagging feeling that all Portuguese stakeholders are aware of what is needed to improve the current state of clinical trials in Portugal, but a strategic agenda is still needed, to reunite all agents. Maybe someone who steps up and takes the role of a leader is necessary.

Sources:

PWC study on Belgium

PWC study on Poland 

EC best practices legislation recommendations 

APIFARMA studies

6 comments
  1. gurjendersihe2012 said:

    Thank you for sharing valuable information. Nice post. I enjoyed reading this post. The whole blog is very nice found some good stuff and good information here Thanks..Also visit my page FMCG Companies jobs .,,,,,,,,,,,,

  2. lívia Sousa said:

    Thanks for your paper I´de liked it. Portugal need beeing more involved in clinical trials
    Lívia Sousa CHUC- Centro de Ensaios Clínicos Coimbra Portugal

    • Dear Lívia Sousa, thank you for your kind comment! Yes, as a trainee in clinical trial coordination at the Neurology Clinical Research Unit of the Hospital Santa Maria, I feel very strongly that hospitals should be more open to clinical trials.

  3. Norma Portugal said:

    I liked your post a lot!
    It gives an idea on what does it takes to do Clinical Research in Portugal and we can understand how an EU country can face difficulties way too different from other countries in the EU.
    You know, it is sad, but Portugal looks like having the same issues than Latin America countries.
    I am a CRA from Mexico, and I felt you were describing our region!!
    Hopefully Clinical Research culture and processes can improve worldwide, as you said, it is a great opportunity in terms of economy and health that is unknown for the majority of people.
    Congratulations!
    Norma Portugal – Sr. CRA Chiltern International

    • Dear Norma,

      Thank you! This is a old piece I wrote three years ago! Definitely in need of a few updates, but most of the issues still remain. Contract approval at sites is still slow, there is still the lack of a clinical trial culture in physicians, and the lack of support structures for researchers ad physicians wishing to do trials or observational studies. It is curious that CROs are now popping up in Portugal (NOVA CRU, Scientific Toolbox for example) that offer to provide help to researchers in conducting investigator driven trials.

      Hit me up on Linkedin! I really enjoy seeing the perspective of other countries in regards to clinical reserach, and what they feel about Portugal.

      https://www.linkedin.com/in/m%C3%A1rcio-barra-4295a958?trk=nav_responsive_tab_profile_pic

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