Paraguay's Clinical Research Landscape for Medtech Early Feasibility Studies
In the rapidly evolving landscape of medical device development, early feasibility studies have become a cornerstone of innovation. These studies, often conducted as first-in-human trials, offer invaluable insights into device safety and performance at a crucial stage of development. Paraguay, a lesser-known player in Latin America's clinical research scene, is emerging as an attractive destination for medtech companies looking to conduct these pivotal studies.
Paraguay's growing prominence in clinical trials for medical devices stems from its unique combination of factors. The country boasts a diverse patient population, a developing regulatory framework, and a burgeoning research infrastructure that appeals to both established medical device companies and clinical trial startups. This article delves into Paraguay's clinical research landscape, exploring its regulatory environment, patient demographics, and the expertise of local investigators. It also examines the ethical considerations and cost advantages that make Paraguay an increasingly popular choice for early feasibility studies in the medical device sector.
The Rise of Early Feasibility Studies
Early Feasibility Studies (EFS) have emerged as a critical step in the medical device development process, allowing investigators to gain early clinical experience with innovative technologies before starting larger clinical trials [1]. The FDA's EFS program, launched in 2014, has been instrumental in supporting device innovation and increasing patient access to potentially beneficial new technologies [2].
Approximately 60 new EFS IDE submissions are reviewed each year by the FDA, with over 70% of EFS IDEs approved within 30 calendar days [2]. Since the program's inception, more than 430 EFS IDEs have been approved, involving over 4,000 study participants [2].
Global Trends
The rising prominence of EFS reflects a global shift in the clinical research landscape. Historically, feasibility studies were often conducted outside the United States due to perceived resource constraints and requirements associated with US study conduct [1]. This led to delays in US patient access to beneficial new devices and limited hands-on experience for US physicians and clinical sites with new products [2].
FDA's EFS Program
To address these issues and promote public health by improving US patient access to new devices, the FDA launched the EFS program as part of its commitment to strengthening the clinical trial enterprise [2]. The program provides a regulatory toolkit containing new recommendations and policies to help study sponsors communicate the information needed to move from bench to bedside under an approved EFS IDE [2].
The FDA has actively promoted the EFS program through direct outreach to sponsors and partnerships with stakeholders like the Medical Device Innovation Consortium [2]. EFS are currently being used across all CDRH device areas, demonstrating the program's broad applicability and impact [2].
Benefits for Medical Device Companies
For medical device companies, conducting an EFS in the United States offers several key benefits:
Early and ongoing interactions with FDA staff that promote collaboration with device developers, industry sponsors, and clinical investigators [2]
Streamlined transition to pivotal trials and accelerated progress towards marketing authorization, particularly for devices intended for the US market [2]
First-in-world access to potentially beneficial medical devices for US patients [1]
Familiarizing regulatory review teams and care providers with the technology earlier in the product development process, applying a learn-as-you-go approach [1]
The EFS program has become a cornerstone of innovation in the rapidly evolving landscape of medical device development [3]. As the FDA continues to support the growth of the program and work collaboratively with sponsors, investigators, and patient advocates, the number of EFS IDEs is expected to increase further in the coming years [2].
Paraguay's Clinical Research Landscape
Paraguay's clinical research landscape has been shaped by a combination of historical factors, current challenges, and future opportunities. Despite severe and unequal gaps in access to the country's public health system, there is a growing interest in enhancing health research in Paraguay [4].
Paraguay's investment in research and development (R&D) as a percentage of its gross domestic product (GDP) was 0.15% in 2017, ranking it 8th out of 12 South American countries [5]. This underfunding poses a serious problem in a country where seven out of 10 people have no health insurance and generally rely on the Ministry of Public Health and Social Welfare for healthcare [4].
The gaps in access to healthcare are exacerbated by discrimination faced by certain groups like transgender women and Indigenous people [4]. Informal workers, who are often more vulnerable during medical emergencies, also face barriers to accessing health insurance [4].
Historical Context
Historically, Paraguay's clinical research activity has been limited. In 2018, the country ranked 10th out of 12 South American countries in total number of publications and cumulative h-index score [4]. The number of clinical trials registered on ClinicalTrials.gov with Paraguayan investigators from 2005 to 2021 was 52, with only 16 ongoing recruiting studies in 2021 [4].
Some of the main historical barriers identified include low incentives for academic careers and a lack of experience in pharmaceutical research [4]. There has also been a necessity to develop a straightforward normative framework for clinical research [4].
Current State of Affairs
In recent years, Paraguay has taken steps to enhance its clinical research capabilities. The development of two research initiative programs, PRONII and PROCIENCIA, by the National Council of Science and Technology (CONACYT) has been associated with higher budget allocation and an increase in the total number of publications from 2011 to 2017 [4].
A survey of ethical review boards (ERBs) in Paraguay found that most were based in universities (61%) and public healthcare institutions (21%) [4]. However, the composition of these ERBs often lacked multidisciplinary representation, with lawyers, social scientists, and community members being underrepresented [4].
Paraguay's regulatory framework for clinical research is overseen by the National Health Regulation Department (DINAVISA). As of 2020, there were no further registered regulations approved by DINAVISA to organize research activities since its creation in 1997 [4]. Applicable legislation includes MERCOSUR Resolution 129/96, ICH guidelines, CIOMS Ethical Guidelines, and the Helsinki Declaration [4].
Some medical device companies have conducted clinical trials in Paraguay. For example, Phagenesis Ltd, a UK-based company developing treatments for dysphagia, conducted a first-in-human study of its Phagenyx® System in Paraguay . Neuromodulation company Mainstay Medical has also established clinical trial sites in Paraguay for studies of its ReActiv8® implantable neurostimulation system [6].
Future Projections
There is a growing interest in enhancing health research in Paraguay, as evidenced by the creation of specific programs that encourage collaboration between healthcare providers, basic scientists, and private investors [4]. However, a comprehensive approach is needed to strengthen regulatory agencies and attract external sponsorship [4].
Interviewees in a qualitative study highlighted the need for a centralized policy to promote R&D, which incorporates training for investigators and ERBs, the development of standardized procedures, and the dissemination of research activities [4]. Sponsor associates underlined that real-world evidence may represent a distinctive opportunity to enhance local research [4].
While modern topics like artificial intelligence, real-world data, and translational research may represent key opportunities to seek investment, special policies should be adopted to prioritize research on the determinants of health in the Paraguayan population [4]. Coordinated efforts are needed to break the unvirtuous cycle and foster a scientific production that responds to the population's needs [4].
Regulatory Framework for EFS in Paraguay
Paraguay has established a robust regulatory framework for the approval of clinical studies, as outlined in Resolution 614 of December 2016 by the Ministry of Health [7]. This resolution has played a crucial role in attracting medical device companies to conduct their early feasibility studies (EFS) and first-in-human (FIH) trials in the country.
Several U.S. medical device companies have successfully initiated EFS and FIH clinical trials in Paraguay, including Vascudyne, Inc., which announced the successful first-in-human use of its TRUE vascular graft in end-stage renal disease patients requiring hemodialysis access in 2021 . NuVera Medical also initiated its FIH clinical trial in Paraguay to evaluate the performance of its NuVision intracardiac echocardiography (ICE) catheter in 2020 . Artio Medical successfully completed the FIH use of its Amplifi vein dilation system in Paraguay in 2021 [6].
Key Regulations
The Ministry of Health in Paraguay has implemented a comprehensive regulatory framework for the approval of clinical studies through Resolution 614 of December 2016 [7]. This resolution outlines the requirements and processes for conducting clinical trials in the country, ensuring the safety and well-being of study participants while facilitating medical research and innovation.
Approval Timelines
According to local experts, the timeline for a study to be approved in Paraguay is typically three to four months. However, with the right government contacts, the approval process can be expedited to as little as one week [7]. This streamlined approval process has made Paraguay an attractive destination for medical device companies looking to conduct EFS and FIH trials efficiently.
Documentation Requirements
To conduct a clinical trial in Paraguay, medical device companies must submit the necessary documentation to the Ministry of Health for review and approval. The specific documentation requirements are outlined in Resolution 614 of December 2016 [7]. These requirements ensure that the proposed study adheres to ethical guidelines, protects patient safety, and follows proper scientific protocols.
While Paraguay's regulatory framework has attracted medical device companies, there are industry concerns about corruption in the country's clinical trial regulatory approval process and light oversight of good clinical practices (GCPs) [8]. Companies that prioritize conducting clinical studies above reproach may have limited interest in conducting trials in Paraguay due to these concerns [8].
Despite these challenges, Paraguay has emerged as a popular destination for cardiovascular medical technology EFS and FIH trials, largely due to the presence of internationally renowned cardiovascular surgeon Dr. Adrian Ebner. Dr. Ebner, who trained in France, has been involved in more than 70 first-in-human studies for products that have gone on to receive CE marks, FDA approvals, or have been acquired by large medical device companies [9].
In conclusion, Paraguay's regulatory framework for EFS, as established by Resolution 614 of December 2016, has streamlined the approval process for clinical trials in the country. While concerns about corruption and light oversight of GCPs persist, the presence of experienced investigators like Dr. Adrian Ebner has made Paraguay an attractive destination for medical device companies conducting EFS and FIH trials, particularly in the cardiovascular space.
Patient Population and Demographics
Paraguay's population of approximately 7.2 million is characterized by a diverse genetic background and a high prevalence of certain diseases, making it an attractive location for early feasibility studies (EFS) in the medical device sector.
Disease Prevalence
Specific endemic diseases, such as tuberculosis, yellow fever, and penile cancer, are particularly prevalent in Paraguay compared to other countries in the region [9] . This high disease burden presents opportunities for conducting impactful research on innovative medical devices aimed at addressing these health challenges.
For example, the incidence of tuberculosis in Paraguay was 41 new cases per 100,000 population in 2021, and the overall tuberculosis mortality rate was 4.5 per 100,000 in 2019 [10]. Yellow fever and penile cancer also have a significant impact on public health in the country.
Genetic Diversity
Paraguay's population is predominantly of mestizo origin, resulting from the admixture of Spanish colonizers, indigenous Guaraní, and a small number of African slaves [11] [12] [13]. Genetic studies have shown that modern-day Paraguayan mestizos are genetically closer to Spaniards than to native Guaraníes, suggesting a Spanish genetic predominance [14].
However, the country also has a significant indigenous population, accounting for 1.7% of the total population in 2012 [14]. This genetic diversity may influence the response to medical interventions and is an important consideration for EFS.
Socioeconomic Factors
Socioeconomic factors play a crucial role in shaping Paraguay's clinical research landscape. In 2020, 26.9% of the population lived below the national poverty line, a decrease from 36.8% in 2001 [10]. Despite improvements, poverty remains a significant challenge, particularly in rural areas.
Income inequality also affects access to healthcare services. In 2014, 94.8% of the poorest quintile lacked health insurance, compared to 40.6% in the least poor quintile [4]. These disparities highlight the need for innovative medical devices that are accessible and affordable for the Paraguayan population.
Several medical device companies have recognized the potential of conducting clinical trials in Paraguay:
Vascudyne, Inc. announced the successful first-in-human use of its TRUE vascular graft in end-stage renal disease patients requiring hemodialysis access in 2021 [4].
NuVera Medical initiated its first-in-human clinical trial in Paraguay to evaluate the performance of its NuVision intracardiac echocardiography (ICE) catheter in 2020 [4].
Artio Medical successfully completed the first-in-human use of its Amplifi vein dilation system in Paraguay in 2021 [4].
These examples demonstrate the growing interest in leveraging Paraguay's unique patient population and demographics for early feasibility studies in the medical device sector.
Research Infrastructure in Paraguay
Paraguay's research infrastructure has been steadily developing in recent years, attracting medical device companies to conduct early feasibility studies (EFS) and first-in-human (FIH) trials in the country. The presence of experienced investigators like Dr. Adrian Ebner, who has been involved in more than 70 FIH studies for products that have gone on to receive CE marks, FDA approvals, or have been acquired by large medical device companies, has been a key factor in this growth [9].
Several medical device companies have successfully conducted clinical trials in Paraguay:
Vascudyne, Inc. announced the successful first-in-human use of its TRUE vascular graft in end-stage renal disease patients requiring hemodialysis access in 2021 .
NuVera Medical initiated its first-in-human clinical trial in Paraguay to evaluate the performance of its NuVision intracardiac echocardiography (ICE) catheter in 2020 .
Artio Medical successfully completed the first-in-human use of its Amplifi vein dilation system in Paraguay in 2021 [6].
These examples demonstrate the growing interest in leveraging Paraguay's research infrastructure for early feasibility studies in the medical device sector.
Clinical Trial Sites
Paraguay has a number of clinical trial sites capable of conducting EFS and FIH studies. The Italian Hospital in Asunción, where Dr. Adrian Ebner serves as the director of endovascular and cardiovascular surgery, has been a popular site for cardiovascular medical technology trials [9]. Other hospitals and clinics in the country have also been involved in medical device clinical research. A medical device CRO in Paraguay will be able to help you search and select the best clinical trial site for your study.
Laboratory Facilities
Paraguay's laboratory facilities have been expanding to support the growing clinical research activity in the country. These facilities provide essential services such as sample processing, storage, and analysis for clinical trials. The availability of reliable laboratory infrastructure is crucial for ensuring the quality and integrity of clinical trial data.
Data Management Capabilities
Effective data management is a critical component of successful clinical trials. Paraguay has been investing in its data management capabilities to support the increasing demand for clinical research services. This includes the implementation of electronic data capture (EDC) systems and the training of personnel in data management best practices.
For example, SGS, a global contract research organization (CRO), recently adopted Veeva Vault EDC to improve site data capture and quality for faster study cycle times during clinical trials [15]. The use of advanced data management tools like Veeva Vault EDC enhances Paraguay's ability to monitor and manage trials with real-time, reliable data from research sites.
In addition to EDC systems, Paraguay has also been exploring the use of innovative data management solutions. The Ministry of Health, in collaboration with the USAID-supported Meeting Targets and Maintaining Epidemic Control (EpiC) project, recently launched a DHIS2-based system to monitor pressure swing adsorption (PSA) plants and oxygen production in the country [16]. While not directly related to medical device trials, this initiative demonstrates Paraguay's commitment to leveraging technology for improved data management in the healthcare sector.
As Paraguay continues to strengthen its research infrastructure, including clinical trial sites, laboratory facilities, and data management capabilities, it is well-positioned to attract more medical device companies seeking to conduct early feasibility studies and first-in-human trials in the region.
Investigator Expertise and Training
Paraguay's growing prominence in the clinical research landscape for medical devices can be attributed, in part, to the expertise of its local investigators. These investigators bring a unique combination of qualifications, training, and international collaboration to the table, making them well-equipped to conduct early feasibility studies (EFS) and first-in-human (FIH) trials.
One notable example is Dr. Adrian Ebner, an internationally renowned cardiovascular surgeon based at the Italian Hospital in Asunción. Dr. Ebner, who trained in France, has been involved in more than 70 FIH studies for products that have gone on to receive CE marks, FDA approvals, or have been acquired by large medical device companies [9]. His extensive experience and expertise have made him a sought-after investigator for cardiovascular medical technology trials.
Several medical device companies have successfully conducted clinical trials in Paraguay, leveraging the expertise of local investigators:
Vascudyne, Inc. announced the successful first-in-human use of its TRUE vascular graft in end-stage renal disease patients requiring hemodialysis access in 2021 .
NuVera Medical initiated its first-in-human clinical trial in Paraguay to evaluate the performance of its NuVision intracardiac echocardiography (ICE) catheter in 2020 .
Artio Medical successfully completed the first-in-human use of its Amplifi vein dilation system in Paraguay in 2021 [6].
Qualifications of Local Investigators
Investigators in Paraguay must meet specific eligibility requirements to participate in clinical research training programs like the Clinical Research Training Institute in Latin America (CRTI-LA). These requirements ensure that investigators have the necessary clinical experience and research potential to conduct high-quality studies.
To be eligible for CRTI-LA, applicants must:
Be a clinician (medical doctor, nurse, psychologist, etc.) with a clinical practice in benign or malignant hematology [17].
Be a fellow or have a current faculty appointment within 15 years from the first faculty appointment in a division or department of hematology or oncology in Latin America [17].
Be fluent in written and spoken English [17].
Training Programs
Training programs like CRTI-LA play a crucial role in developing the skills and knowledge of local investigators. The two-day, highly-interactive in-person workshop covers topics such as biostatistics, literature searching, registry development, and conducting research in Latin America [17]. Participants also have the opportunity to develop a potential capstone project and receive individualized mentorship from program faculty [17].
The Universidad Nacional de Asunción (UNA) School of Medicine also offers enriching programs for visiting practicing physicians, fellows, residents, and medical students. The Visiting Medical Student Program and Observer Training Program provide strong clinical experiences and an overview of the Paraguayan medical system [18].
Collaboration with International Experts
Collaboration with international experts is another key factor in the development of investigator expertise in Paraguay. Dr. Adrian Ebner's training in France and involvement in numerous international studies highlight the importance of these collaborations [9].
The Universidad Nacional de Asunción (UNA) School of Medicine's programs for visiting physicians and students also foster international collaboration and knowledge exchange [18]. These programs allow local investigators to learn from and work alongside experts from around the world, enhancing their skills and expertise.
In conclusion, the expertise of local investigators, combined with targeted training programs and international collaboration, has positioned Paraguay as an attractive destination for early feasibility studies and first-in-human trials in the medical device sector. As more companies recognize the potential of conducting clinical trials in Paraguay, the country's role in the global clinical research landscape is likely to continue growing.
Ethical Considerations in Paraguayan EFS
Conducting early feasibility studies (EFS) in Paraguay requires adherence to ethical principles and guidelines to protect the rights, safety, and well-being of study participants. The informed consent process is a critical component of ethical research, ensuring that participants are fully informed about the study and voluntarily agree to participate [4].
In Paraguay, the informed consent process upholds the basic ethical principle of "autonomy" in human research. The informed consent document (ICD) consists of two parts: the "subject information sheet" and the "informed consent form" (ICF), which must be approved by the Institutional Ethics Committee (IEC) before administration [4]. The content of the ICD should be brief, lucid, non-technical, and simple enough for the participant to understand [4].
Consent should be obtained without any coercion, and in cases where a participant is unable to provide informed consent (e.g., unconscious, minor, or those suffering from severe mental illness or disability), it must be obtained from a legally acceptable representative (LAR) [4]. If the participant or LAR is unable to read/write, an impartial witness should be present during the entire informed consent process and must append their signatures to the consent form [4].
For children under 7 years old, verbal consent is essential, and for mature minors (aged 7-18 years), informed assent should be obtained [4]. The informed consent process is crucial for safeguarding the autonomy of a person regarding their willingness to participate in a trial and rebuilding trust between the physician and study participants [4].
Vulnerable Populations
Special considerations must be made when conducting EFS in vulnerable populations, such as those with incurable diseases, in nursing homes, in detention, unemployed or impoverished, prisoners, students, service personnel, in emergency rooms, homeless persons, nomads, refugees, and any ethnic or racial minority groups [4]. These individuals should not be included unless the research is essential to promote the health of the population represented, and the research cannot be performed on other participants [4].
Pregnant or nursing women should only be included if the drug in the trial is intended to be used by pregnant or nursing mothers or fetuses, and data on non-pregnant women are unsuitable [4]. Such research should carry less than minimal risk to the developing fetus, and these participants should not be unnecessarily debarred from the benefit of investigations, drugs, vaccines, or other agents that promise therapeutic or preventive benefits during pregnancy or lactation [4].
Post-Trial Access to Treatment
Ethical considerations extend beyond the duration of the EFS, and post-trial access to treatment is an important aspect to consider. The Declaration of Helsinki, which Paraguay has signed, emphasizes that "at the conclusion of the study, patients entered into the study are entitled to be informed about the outcome of the study and to share any benefits that result from it, for example, access to interventions identified as beneficial in the study or to other appropriate care or benefits" [12].
Ensuring post-trial access to treatment is particularly important in low- and middle-income countries like Paraguay, where access to healthcare may be limited [13]. Sponsors and researchers should engage with local communities and health authorities to develop plans for post-trial access to interventions that are found to be beneficial in the EFS [13].
In conclusion, conducting EFS in Paraguay requires a strong commitment to ethical principles, with a focus on informed consent, protection of vulnerable populations, and post-trial access to treatment. By adhering to these ethical considerations, researchers can ensure that the rights and well-being of study participants are prioritized throughout the EFS process.
Conclusion
Paraguay's emerging role in early feasibility studies for medical devices highlights its growing importance in the global clinical research scene. The country's diverse patient population, developing regulatory framework, and experienced investigators like Dr. Adrian Ebner have made it an attractive destination for innovative medical technology trials. Several companies, including Vascudyne, NuVera Medical, and Artio Medical, have successfully conducted first-in-human studies in Paraguay, showcasing its potential to drive healthcare innovation forward.
As Paraguay continues to strengthen its research infrastructure and address ethical considerations, it is well-positioned to play a crucial part in advancing medical device development. The country's unique combination of factors offers valuable opportunities for companies looking to conduct early-stage clinical trials efficiently and effectively.
With ongoing improvements in its clinical research landscape, Paraguay is set to make significant contributions to the field of medical device innovation in the years to come.
To accelerate your development process and drive healthcare innovation forward, contact bioaccess® today to learn how our comprehensive medical device CRO services in Paraguay can help.
References
[1] - https://mdic.org/program/early-feasibility-studies-efs/
[2] - https://mdic.org/celebrating-the-early-feasibility-studies-programs-10-year-journey/
[3] - https://www.avaniaclinical.com/blog/is-the-fdas-efs-program-right-for-your-medical-device/
[4] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687402/
[5] - https://www.meddeviceonline.com/doc/latam-s-regulatory-framework-for-medtech-early-feasibility-studies-0001
[6] - https://aws.amazon.com/financial-services/security-compliance/compliance-center/py/
[7] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625094/
[8] - https://wwwnc.cdc.gov/eid/article/27/5/20-4244_article
[9] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11004369/
[10] - https://hia.paho.org/en/node/160
[11] - https://www.researchgate.net/publication/375704700_Breaking_the_unvirtuous_cycle_barriers_and_opportunities_for_research_and_development_in_Paraguay_A_case_study
[12] - https://www.worldbank.org/en/country/paraguay/overview
[13] - https://www.clinicalleader.com/doc/latin-america-s-landscape-for-medtech-clinical-trials-0001
[14] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303215/
[15] - https://www.sgs.com/en-py/news/2022/06/sgs-advances-clinical-trial-data-management-with-veeva-vault-edc
[16] - https://epicproject.blog/paraguay-launches-first-of-its-kind-digital-system-to-track-medical-oxygen/
[17] - https://www.hematology.org/awards/career-enhancement-and-training/clinical-research-training-institute-latin-america
[18] - https://medicine.hsc.wvu.edu/tropmed/global-health-rotations/paraguay/
