Vinicius Ernani, MD
Carlos H. Barrios, MD
CLINICAL TRIALS are an essential research tool to advance medical knowledge and patient care. Traditionally, the majority of pharmaceutical-sponsored clinical trials have been implemented in Western Europe and North America. More recently, however, large pharmaceutical companies have increased their operational activities to include Latin America, Eastern Europe, and Asia.
Over the past 20 years, the number of active U.S. Food and Drug Administration (FDA)-regulated investigators based outside of the United States has increased by 15% yearly, whereas the number of U.S. investigators has decreased by 5.5%.1 In Brazil, for instance, the average relative annual growth rate has been around 16%.2 Nevertheless, according to ClinicalTrials.gov, only 201 clinical trials are currently open and recruiting patients with cancer in Brazil. This number significantly contrasts with the 6,337 recruiting studies in the United States.
Brazil is the 9th largest economy in the world. However, this beautiful South American country is facing tremendous hurdles ranging from basic educational needs, discrepancies in wealth distribution, and a broken public health-care system to an unprecedented history of corruption that plagues the country. In 1990, a health reform was implemented and the “Sistema Único de Saúde” (SUS)–Unified Health System was created based on decentralized universal access, with municipalities providing comprehensive and free health care to each individual in need financed by the states and federal government.3 This system is responsible for approximately 75% of the high-complex medical procedures performed in the country, and it’s without cost for any person.4 Given the current economic recession and political challenges in Brazil, the 2016 federal budget for Brazil’s universal health-care system has decreased by $1.1 billion dollars.
In contrast to the United States, where the overall cancer death rate has decreased by 13% from 2004 to 2013,5 cancer mortality is still increasing in most regions of Brazil. Plausible explanations for this rise include poor prevention strategies, late diagnosis, and lack of access to optimal diagnosis and treatment. Within this complex scenario, addressing the current situation of cancer clinical research in Brazil represents a challenge.
Barriers to Clinical Research Development
MOST OF CANCER clinical research conducted in this South American country is sponsored by the pharmaceutical industry. Investigator-initiated trials are still limited and need to be stimulated. In this context, the priority step is to build a “research culture” among government, hospitals, providers, and patients. Although the medical community is reasonably sensitized regarding the importance of developing clinical research, patients, institutions, and political entities are lagging far behind.
“Less than 1% of phase I cancer clinical trials are being conducted in Latin America, because of delays at the regulatory level.”— Vinicius Ernani, MD, and Carlos H. Barrios, MD
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For instance, the regulatory process to open a clinical trial in Brazil could take more than 12 months. Government’s mistrust toward the pharmaceutical industry and the lack of knowledge from the political leaders are important culprits of this inefficient and disorganized regulatory system. Less than 1% of phase I cancer clinical trials are being conducted in Latin America, because of delays at the regulatory level. Brazil has only 34 phase I clinical trials open for cancer patients.6 Changing the culture is a large-scale undertaking, and eventually all of the entities involved will need to collaborate in a multidisciplinary strategically designed effort.
Some of the other critical barriers that impose limits to the country’s clinical research development are the absence of reliable cancer registries (only 6% of the Latin America population is covered by population-based cancer registries), primitive cooperative research groups, lack of public and private funding, and very limited information provided to patients about clinical trials. It is important to recognize that Brazil is not alone facing these economic, social, and political dilemmas. Most of the issues and challenges described here are also present in the majority of Latin American countries, which encompass more than 600 million people.
Improving Brazil’s Participation in Clinical Research
WHAT ARE SOME of the positive measures the country is taking to advance oncology clinical research? Fortunately, there is a light at the end of the tunnel. Politically, in February 2017, the Senate approved a new law, which will significantly expedite the regulatory process for clinical trials. Even though still requiring approval by the House of Representatives, the new legislation is already having an impact, with some trials obtaining approval in less than 6 months and enabling the enrollment of some of the first study patients in the world. Hopefully, this measure will also allow the country to engage more in phase I clinical trials. Clinically, Brazil has a considerable number of world-class investigators and well-experienced audited clinical research sites with a broad experience in phase II and III clinical trials. Thus, the combination of experienced investigators, allied to a population of 200 million people and no competitive trials, is certainly a desirable niche.
Last, but not least, a few cooperative cancer research initiatives have been developed in South America and include groups such as the Argentine Group for Clinical Research in Oncology, the Uruguayan Oncology Cooperative Group, the Peruvian Oncology Clinical Studies Group, the Brazilian Group of Breast Cancer Studies, the Chilean Cooperative Group for Oncologic Research, among others.7 The Latin American Cooperative Oncology Group (LACOG), based in Porto Alegre, Brazil, is one of such initiatives, which congregates investigators and centers from 15 different countries in South America. The group intends to stimulate the development of investigator-initiated trials, epidemiologic data, and international collaboration. LACOG includes 225 investigator members distributed in 11 institutions and reports 21,000 new cancer patients per month of whom fewer than 200 are enrolled in clinical trials. These numbers represent the unexplored potential for clinical cancer research in Brazil and South America.
“Brazil has highly qualified oncology scientists, new promising cooperative groups, and a big population that deserves the latest treatments and opportunities. However, the country needs to change the negative perceptions regarding the impact of clinical trials.”— Vinicius Ernani, MD, and Carlos H. Barrios, MD
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Clinical trials are very welcome in Brazil and South America. They are certainly an extraordinary path to improve clinical care in the region, build infrastructure, facilitate access to technology, and advance science. Brazil has highly qualified oncology scientists, new promising cooperative groups, and a big population that deserves the latest treatments and opportunities. To become a reality, however, the country needs to change the negative perceptions regarding the impact of clinical trials. This organizational cultural change remains incipient; nevertheless, it needs to be accomplished at all hierarchical levels. As the business expert and author Daniel Ally said: “To change your reality, you need to change your mentality.” ■
DISCLOSURE: Drs. Ernani and Barrios reported no potential conflicts.
REFERENCES
1. Getz KA: Global clinical trials activity in the details. September 1, 2007. Available at www.appliedclinicaltrialsonline.com/node/230040?rel=canonical. Accessed November 20, 2017.
2. Thiers FA, Sinskey AJ, Berndt ER: Trends in the globalization of clinical trials. Nat Rev Drug Discov 7:13-14, 2008.
3. Paim J, Travassos C, Almeida C, et al: The Brazilian health system: History, advances, and challenges. Lancet 377:1778-1797, 2011.
4. SUS: The health of Brazil. Available at www.ccms.saude.gov.br/SUS20anos/ mostravirtual/index.php. Accessed November 20, 2017.
5. SEER cancer statistics review, 1975-2013. Available at https://seer.cancer.gov/ archive/csr/1975_2013/. Accessed November 20, 2017.
6. ClinicalTrials.gov. Available at clinicaltrials.gov. Accessed November 20, 2017.
7. Barrios CH, Werutsky G, Martinez-Mesa J: The global conduct of cancer clinical trials: Challenges and opportunities. Am Soc Clin Oncol Educ Book e132-e139, 2015.
