By Julio G. Martinez-Clark, CEO, bioaccess
Clinical research has changed in the past two decades, shifting from industrialized Western countries to so-called emerging or low-income and middle-income countries (LMICs) in Eastern Europe, Latin America, and Africa.1 The globalization of research is receiving considerable attention due to the increasing number of offshored research and development (R&D) activities from the United States, Europe, and Japan. Recent studies have challenged the traditional thinking of cost-related factors as the primary reason for offshoring clinical trials. They have shown the importance of the recruitment of human subjects in trials. The “recruitment crisis” in the home country seems to be the main contribution to and a key driver of offshore clinical research activities.2
This article examines the need to conduct clinical trials outside the U.S. (OUS), addresses the recruitment crisis in the U.S., reviews the incentives for clinical trials overseas, and explores the growth of clinical trials in Latin America. We will profile Colombia as an example of a country committed to attracting more foreign investment in clinical trials.
The Recruitment Crisis In The U.S. And The Need For OUS Clinical Trials
Patient recruitment is known to be one of the most challenging aspects of conducting a clinical trial. Inadequate subject retention during the conduct of trial affects conclusive results.2 The main factors that prevent drug and medical device manufacturers from conducting clinical trials in the U.S. include:
- Recruiting subjects is challenging (fewer feel the need to participate).3
- There is a higher and costlier standard of care and operational and administrative staff are more expensive.3
- Busy specialists are unwilling to dedicate their time and dedication to unproven medical products.3
- There is mistrust based on the infamous Tuskegee Syphilis Study: Between 1932 and 1972, vulnerable subjects were not informed of the nature of the trial, and more than 100 died. This was a major violation of ethical standards and has been cited as "arguably the most infamous biomedical research study in U.S. history.” 3,4
- The Health Insurance Portability and Accountability Act of 1996 (HIPAA) strict privacy rule has had a substantial, negative influence on the conduct of clinical research, often adding uncertainty, cost, and delay.3,5
- The availability of alternative FDA-approved palliative therapeutic options makes subjects think twice before participating in a trial with an unproven therapeutic (especially in phase I or first-in-human studies).
- Industry data reveals that 35 percent of delays in clinical trials are due to a lack of subject recruitment, nearly one-fifth of investigators do not enroll any subjects, and about one-third of investigators enroll only five percent of eligible subjects.6
Several factors drive manufacturers to conduct clinical trials outside the U.S. (OUS or foreign clinical trials, FCTs):
- Easier and faster subject recruitment3
- Reduced costs3
- Motivated investigators eager to participate and publish results3
- Wide availability of patients interested in participating because they have difficulty accessing their national universal healthcare systems (i.e., delayed appointments, delayed approvals for high-cost procedures). This translates to the availability of larger subject pools and faster recruitment rates.3
- Countries and hospitals eager to attract foreign investment in clinical research (e.g., Colombia, Korea, Denmark, Norway)3
- Availability of local CROs connected with potential investigators and hospitals3
- Less regulatory red tape3
- Drug shortages create a narrow range of therapeutic options in the local market;7 thus incentivizes subjects to participate in clinical trials with innovative therapies that otherwise would not be available.
As a result, ClinicalTrials.gov reveals that 52 percent of global clinical trials take place outside the U.S.
The challenges faced by developed countries are making LMICs in Asia, Latin America, Central, and Eastern Europe, the Middle East, and Africa preferable centers for conducting clinical trials in all phases.8 LMICs are pushing to expand their involvement in all stages of drug and medical device development, primarily as a source of revenue.9
Latin America Is Emerging As A Desirable Clinical Trial Destination
There are many factors to consider when selecting a clinical trial destination, and Latin America is now one of the most desirable places for clinical research. Due to several factors including its ethnically diverse population and solid doctor-patient relations, Latin America has become one of the most attractive locations for international clinical trials.10 Latin America supports about 10 percent of clinical research worldwide.11 According to the Pan American Health Organization (PAHO), 202 (10.2 percent) of the global COVID-19 clinical trials were conducted in Latin America.12
The pharmaceutical industry invested approximately $980 million in clinical trials in Brazil, Argentina, and Mexico in 2019 (together representing 70 percent of the clinical trials in Latin America). Colombia and Chile received an additional 20 percent of clinical trials, and the remaining 10 percent were in Peru, Costa Rica, Panama, and Guatemala.13 In 2019 alone, the pharmaceutical industry financed almost 700 clinical studies in Latin America and has made investments of more than $1 billion in the same year.13 In 2020, there were 31 medical device trials in Latin America – an explosive 138 percent increase from 17 in 2017!14 In addition, GlobalData shows that now about 1 percent of the global medical device clinical trials happen in Latin America.15
Latin America has over 650 million people; over 80 percent of them live in urban areas.16 Latin America is now the planet’s most urbanized region. By 2050, 90 percent of Latin Americans will live in cities. Today, there are more than 55 cities with a population of 1 million or more, including some of the largest metropolitan areas on the planet. Depending on how one counts, there are roughly 2,000 cities driving Latin America's economy. No part of the world has urbanized more rapidly than Latin America.17
Latin America is one of the less exploited regions for patient recruitment compared to major saturated centers in the U.S. and the EU. Several studies indicate that awareness changes attitudes toward clinical trials, enrollment, and the benefits of participation. In a survey, 85 percent of patients were either unaware or unsure that participation in a clinical trial was an option at the time of diagnosis; and 75 percent of these patients said they would have been willing to enroll had they known it was possible.18 The lack of clinical trial awareness, drug shortages, difficult access to the national public healthcare systems, and the strong bond between patients and physicians make Latin America a fertile ground for subject recruitment and retention. Also, the large metropolitan areas in the region provide subject concentrations for robust enrollment and retention. These factors seem to explain why experts agree that dropout rates in Latin America are one-third of those in the U.S. and the EU.19
Colombia Stands Out As An Opportunity For Clinical Trials
Clinical research brings enormous benefits to a country regarding timely access by subjects to innovative, quality treatments, improving and increasing the medical knowledge base, promoting foreign investment, and generating jobs, conditions that undoubtedly contribute to stimulating social and economic development. With almost 52 million people (80 percent of them in urban areas),21 Colombia stands out as a clinical trial destination in Latin America thanks to its scientific rigor, ethics, and quality. The World Health Organization (WHO) ranks Colombia’s healthcare system 22 out of 191 countries and rates the country's healthcare system as the best in Latin America.22 Colombia offers the necessary guarantees to conduct clinical research of the highest level by having a rigorous level-4 regulatory agency (the FDA is also a level-4 agency) and strict regulations on this matter. Five Colombian research centers have been classified among the 15 best in Latin America.23 Colombia is the only country in Latin America with a GCP institutional-level certification to ensure the quality of the clinical data exported from the country. Colombia boasts 135 certified research centers and 76 certified institutional and central ethics committees.24
In 2019, Colombia hosted 60 industry-sponsored clinical trials, representing over $60 million in foreign investments.13,24 Several global CROs operate in Colombia and maintain open communication with its regulatory agency, INVIMA. The Colombian government has dedicated efforts to improving the clinical research environment to international standards and enhancing its relative attractiveness. Experts agree that Colombia could see over 100 new clinical trials every year and close to $500 million in economic gains per year.25 Colombia offers one of the most generous R&D tax incentives among the members of the OECD and partner economies. Introduced in 2020, the new Colombian R&D tax credit allows small and midsize companies to claim a 50% tax credit of what they spend on R&D and innovation projects investments.26,27
Colombia has recognized these benefits and has an ambitious science, technology, and innovation plan for 2022–2031 to become a knowledge economy.28 Through its investment-promoting agency, ProColombia, Colombia seems to be the only country in Latin America actively promoting itself as a top clinical trial destination in the region.29 Colombia, along with Mexico, Costa Rica, and Chile, is a member of the Organization for Economic Cooperation and Development (OECD) – an intergovernmental economic organization with 38 member countries, founded in 1961 to stimulate economic progress and world trade. OECD membership grants Colombia access to the best economic and social practices aligned with the U.S., Canada, and other advanced member economies, including best practices for international clinical research.30
The patient recruitment crisis in the U.S., its high healthcare costs, and other factors have led drug and medical device manufacturers to seek to conduct clinical trials in LMICs. Reduced costs, easier and faster subject recruitment and faster regulatory approvals have boosted foreign investment in clinical research in Latin America. The government of Colombia seems to be the only country in Latin America with an active initiative to attract more clinical trials as part of its plan to become a knowledge economy by 2031. Colombia has an advantageous geographical location in the Eastern Time Zone; its medical facilities rank highly in regional comparison; it has a pool of close to 52 million people with adequate universal health coverage; it has non-stop flights from the major cities in the U.S.; it has a sizable urban population; it offers competitive costs (the Colombian peso is the most devalued currency in Latin America);31 and the country is recognized for its scientific rigor, ethics, and quality of clinical data.
- Why are emerging countries popular for clinical research? V Strüver, S C Ibeneme. 5, 2021, SAMJ, Vol. 111.
- Kermanimojarad, Maryam. What is the impact of patient recruitment on offshoring of clinical trials? National Library of Medicine. [Online] December 2020. [Cited: April 27, 2020.] https://dx.doi.org/10.1186%2Fs40504-020-00104-4.
- Acceptance of foreign clinical trials data by US FDA. ProRelixResearch. [Online] August 13, 2021. [Cited: April 27, 2022.] https://prorelixresearch.com/acceptance-of-foreign-clinical-trials-data-by-us-fda/.
- Tuskegee Syphilis Study. Wikipedia. [Online] January 16, 2022. [Cited: May 8, 2022.] https://en.wikipedia.org/wiki/Tuskegee_Syphilis_Study.
- Influence of the HIPAA Privacy Rule on Health Research. Ness RB, Joint Policy Committee, Societies of Epidemiology FT. 18, 2007, JAMA, Vol. 298, pp. 2164–2170.
- Country Level Clinical Trial Feasibility: Top 7 Key Areas To Explore. CREDEVO. [Online] June 25, 2020. [Cited: April 29, 2022.] https://credevo.com/articles/2020/06/25/country-level-clinical-trial-feasibility-top-7-key-areas-to-explore/.
- Drug Shortage: Causes, Impact, and Mitigation Strategies. Shukar Sundus, Zahoor Fatima, Hayat Khezar, Saeed Amna, Gillani Ali Hassan, Omer Sumaira, Hu Shuchen, Babar Zaheer-Ud-Din, Fang Yu, Yang Caijun. 2021, Frontiers in Pharmacology , Vol. 12.
- Global migration of clinical research during the era of trial registration. Drain PK, Parker RA, Robine M, Holmes KK, Bassett IV. 2, s.l. : PubMed Central, 2018, PLoS One, Vol. 13.
- The case for conducting first-in-human (phase 0 and phase 1) clinical trials in low and middle income countries. Kapiriri, L., Lavery, J.V., Singer, P.A. et al. 811, October 18, 2011, BMC Public Health, Vol. 11.
- Doubly disadvantaged: on the recruitment of diverse subjects for clinical trials in Latin America, Tapuya. Pinto, Manuela Fernández. 1, s.l. : Taylor & Francis Online, Latin American Science, Technology and Society, Vol. 2, pp. 391-407.
- This is how clinical research is redefined in Latin America . FIFARMA. [Online] April 22, 2021. [Cited: April 30, 2022.] https://fifarma.org/en/this-is-how-clinical-research-is-redefined-in-latin-america/.
- El panorama de los ensayos clínicos sobre COVID-19 en América Latina y el Caribe: evaluación y desafíos. Carracedo S, Palmero A, Neil M, Hasan-Granier A, Saenz C y Reveiz L. e33, s.l. : Pan American Health Organization, 2021, Rev Panam Salud Publica, Vol. 45.
- Valuing the Research-based Pharmaceutical Industry in Latin America. IQVIA Insights. [Online] November 9, 2021. [Cited: April 29, 2022.] https://www.iqvia.com/insights/the-iqvia-institute/reports/valuing-the-research-based-pharmaceutical-industry-in-latin-america.
- ClinicalTrials.gov. [Online] [Cited: 4 27, 2022.] https://clinicaltrials.gov/ct2/results/map?cond=&term=device&strd_s=01%2F01%2F2018&strd_e=12%2F31%2F2018&cntry=&state=&city=
- Market Data. Medical Device Network. [Online] April 12, 2022. [Cited: April 26, 2022.] https://www.medicaldevice-network.com/marketdata/new-medical-device-clinical-trials-q1-2022/.
- Latin America & Caribbean: Urbanization from 2010 to 2020. Statista. [Online] February 22, 2022. [Cited: May 21, 2022.] https://www.statista.com/statistics/699089/urbanization-in-latin-america-and-caribbean/.
- Latin America’s cities are ready to take off. But their infrastructure is failing them. World Economic Forum. [Online] June 7, 2018. [Cited: May 21, 2022.] https://www.weforum.org/agenda/2018/06/latin-america-cities-urbanization-infrastructure-failing-robert-muggah/.
- The Need for Awareness of Clinical Research. National Institutes of Health. [Online] March 16, 2016. [Cited: June 1, 2022.] https://www.nih.gov/health-information/nih-clinical-research-trials-you/need-awareness-clinical-research.
- Why Latin America. COHORTIAS. [Online] [Cited: April 29, 2022.] https://www.cohortias.com/about/why-latin-america-clinical-trials/.
- Study Abroad: Tips for Successful Clinical Trials Outside of the United States. MD+DI. [Online] December 11, 2012. [Cited: April 29, 2022.] https://www.mddionline.com/news/study-abroad-tips-successful-clinical-trials-outside-united-states.
- Colombia Population (LIVE). Worldometer. [Online] May 8, 2022. [Cited: May 8, 2022.] https://www.worldometers.info/world-population/colombia-population/#:~:text=The%20current%20population%20of%20Colombia,the%20latest%20United
- Colombia, a World-class healthcare destination. Business Insider. [Online] October 23, 2020. [Cited: May 8, 2022.] https://markets.businessinsider.com/news/stocks/colombia-a-world-class-healthcare-destination-1029715798.
- Thanks To The Efforts Made By The Different Actors In The Health Sector, Colombia Is A Powerhouse In Clinical Research In Latin America. COHORTIAS. [Online] June 28, 2021. [Cited: April 30, 2022.] https://www.cohortias.com/cro-in-colombia-best-in-clinical-research/.
- Asociación Colombiana de Centros de Investigación Clínica (ACIC). [Online] February 2022. [Cited: May 7, 2022.] https://aciccolombia.org/wp-content/uploads/2022/03/Boletin-6-Febrero-2022.pdf.
- Clinical Trials Policy Annex: Improving Colombia’s Clinical Research Environment. Pugatch Consilium. [Online] 2016. [Cited: May 23, 2022.] https://www.pugatch-consilium.com/reports/Challenges%20and%20Opportunities_Annex_US_v3.pdf.
- R&D Tax Incentives: Colombia, 2021. Organisation for Economic Co-operation and Development (OECD). [Online] December 2021. [Cited: May 22, 2022.] https://www.oecd.org/sti/rd-tax-stats-colombia.pdf.
- Organisation for Economic Cooperation and Development (OECD). OECD. [Online] [Cited: May 1, 2022.] https://www.oecd.org/colombia/.
- CONPES aprobó política de ciencia, tecnología e innovación (CTI). Departamento Nacional de Planeación. [Online] December 27, 2021. [Cited: May 21, 2022.] https://www.dnp.gov.co/Paginas/CONPES-aprobo-politica-de-ciencia-tecnologia-e-innovacion-CTI.aspx.
- PHARMACEUTICAL SECTOR. Invest in Colombia. [Online] [Cited: April 30, 2022.] https://investincolombia.com.co/en/sectors/healthcare-services-and-life-sciences/pharmaceutical-sector.
- OECD. Wikipedia. [Online] April 30, 2022. [Cited: May 7, 2022.] https://en.wikipedia.org/wiki/OECD.
- According to the Big Mac index, Colombia is the country with the most devalued currency in the region. Infobae. [Online] April 20, 2022. [Cited: April 30, 2022.] https://www.infobae.com/en/2022/04/20/according-to-the-big-mac-index-colombia-is-the-country-with-the-most-devalued-currency-in-the-region/.
About The Author:
Julio G. Martinez-Clark is co-founder and CEO of bioaccess, a market access consultancy that works with medical device companies to help them do early-feasibility clinical trials and commercialize their innovations in Latin America. Julio is also the host of the LATAM Medtech Leaders podcast: A weekly conversation with Medtech leaders who have succeeded in Latin America. He serves as an advisory board member for Stetson University's Leading Disruptive Innovation program. He has a bachelor's degree in electronics engineering and a master's degree in business administration.