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BACKGROUND: During the past two years, the COVID-19 pandemic has cost millions of lives around the globe, caused major morbidity and provoked widespread economic and social disruption. In response, governments have enacted policies to mitigate the impacts of the pandemic. This research focuses in on policies aimed at increasing access to essential health products and services by comparing them to the global rules governing trade, investment and intellectual property. We have assessed whether these rules have or could have constrained countries in responding to this and future crises. The study identifies the nature and scope of the trade-related health sector policies implemented by our sample group of countries, selected because of their systemic significance: the United States, Germany, France, China, South Africa and India. Each policy is placed into one of five broad categories covered by trade and investment rules so that we could assess their consistency with those rules. RESULTS: We found, among other things, that the types of trade-related health measures were quite diverse. The high-income countries in our study were the most active in the policy space and tended to rely on subsidies-based measures while the middle-income countries relied more heavily on export and import measures. Policies directly relevant to intellectual property protection were virtually non-existent. When evaluating the implemented policies against the global trade and investment rules, we found potential constraints under five different types of rules: those governing subsidies, import and export trade barriers, investment measures, government procurement and trade-related intellectual property. CONCLUSIONS: Given the tension between the global rules and the practices of policymaking during the pandemic, we conclude that the tension must be resolved in favor of governments making policy rather than relying on existing exceptions or pushing national governments to comply more exactly with the rules. Although the pandemic itself does not respect national borders, governance still generally occurs at the national level because national governments are often the only entities with both the legal authority and the practical ability to respond.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Investimentos em Saúde , Política de Saúde , ChinaRESUMO
BACKGROUND: Insurances in high-income countries (HIC) often contract with private community pharmacies to dispense medicines to outpatients. In contrast, dispensing of medicines in low- and middle-income countries (LMICs) often lacks such contractual arrangements. Furthermore, many LMICs lack sufficient investment in supply chains and financial and human resources to guarantee stock levels and services at public medicine-dispensing institutions. Countries striving to achieve universal health coverage (UHC) can, in principle, incorporate retail pharmacies into their supply chains to expand access to essential medicines (EMs). The objectives of this paper are (a) to identify and analyze key considerations, opportunities and challenges for public payers when contracting out the supply and dispensing of medicines to retail pharmacies and (b) to provide examples of strategies and policies to address these challenges. METHODS: A targeted literature strategy was used to conduct this scoping review. We created an analytical framework of key dimensions: (1) governance (including medicine and pharmacy regulation); (2) contracting (3) reimbursement; (4) medicine affordability (5) equitable access; and (6) quality of care (including 'patient-centered' pharmaceutical care). Using this framework, we selected a mix of three HIC and four LMIC case studies and analyzed the opportunities and challenges encountered when contracting retail pharmacies. RESULTS: From this analysis, we identified a set of opportunities and challenges that should be considered by public payers considering public-private contracting: (1) balancing business viability with medicine affordability; (2) incentivizing equitable access to medicines; (3) ensuring quality of care and delivery of services; (4) ensuring product quality; (5) task-sharing from primary care providers to pharmacies and (6) securing human resources and related capacity constraints to ensure sustainability of the contract. CONCLUSION: Public-private partnerships offer opportunities to improve access to EMs. Nonetheless, managing these agreements is complex and is influenced by a variety of factors. For effective contractual partnerships, a systems approach is needed in which business, industry and regulatory contexts are considered in tandem with the health system. Special attention should be devoted to rapidly changing health contexts and systems, such as changes in patient preferences and market developments brought about by the COVID-19 pandemic.
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Taiwan's National Health Insurance (NHI) is a widely acclaimed universal healthcare system. In the past few years, particularly following the COVID-19 outbreak, challenges related to maintaining the NHI system have surfaced. Since 2020, NHI has faced a series of challenges, including excessive patient visits to the hospital emergency department, a lack of an effective primary care and referral system, and a high turnover rate of healthcare workers. We review major problems related to Taiwan's NHI, emphasizing input from frontline healthcare workers. We provide recommendations for potential policies addressing the concerns around NHI, for example, strengthening the role of primary care services under the NHI administration, reducing the high turnover rate of healthcare workers, and increase the premium and copayments. We hope that this policy analysis may allow policymakers and scholars to understand both the merits and critical problems related to NHI from the clinical perspective.
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COVID-19 , Humanos , Taiwan/epidemiologia , Programas Nacionais de Saúde , Formulação de Políticas , Serviço Hospitalar de EmergênciaRESUMO
Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas.
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Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Mitose , Sarcoma , Telômero , Humanos , Variação Genética , Células Germinativas , Melanoma/genética , Mitose/genética , Sarcoma/genética , Complexo Shelterina/genética , Telômero/genéticaRESUMO
A Community Genetics carrier screening program for the Jewish community has operated on-site in high schools in Sydney (Australia) for 25 years. During 2020, in response to the COVID-19 pandemic, government-mandated social-distancing, 'lock-down' public health orders, and laboratory supply-chain shortages prevented the usual operation and delivery of the annual testing program. We describe development of three responses to overcome these challenges: (1) pivoting to online education sufficient to ensure informed consent for both genetic and genomic testing; (2) development of contactless telehealth with remote training and supervision for collecting genetic samples using buccal swabs; and (3) a novel patient and specimen identification 'GeneTrustee' protocol enabling fully identified clinical-grade specimens to be collected and DNA extracted by a research laboratory while maintaining full participant confidentiality and privacy. These telehealth strategies for education, consent, specimen collection and sample processing enabled uninterrupted delivery and operation of complex genetic testing and screening programs even amid pandemic restrictions. These tools remain available for future operation and can be adapted to other programs.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Manejo de Espécimes/métodos , Consentimento Livre e Esclarecido , Testes GenéticosRESUMO
Background: Patenting medicine-delivery devices (inhalers and pens) is controversial when it extends market protections beyond that of the underlying therapeutic agent. We evaluated how common device patenting is, internationally. Method: Using a product sample (n = 88) and an international patent database, we assessed the issue's scope. Results: When comparing the 88 patent portfolios for each product in each country, Canada was found to be among the most impacted, with 90% of the portfolios containing at least one device patent and 35% of the portfolios containing device patents exclusively. Conclusion: Patenting of delivery devices impacts major pharmaceutical manufacturing centres worldwide. International consensus among stakeholders (regulators and payors) is needed on which device modifications represent meaningful clinical value.
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Preparações Farmacêuticas , Humanos , CanadáRESUMO
BACKGROUND AND OBJECTIVES: High out-of-pocket expenditures (OOPE) increases the probability that households will become impoverished or will forgo needed care. The aim of this paper is to study household medicines expenditure and its associated determining factors to develop policies to protect households from financial hardship. METHODS: The present cross-sectional and population-level study used the Bangladesh 2016-17 National Household Income and Expenditure Survey (HIES). The final sample size was 46,080 households. We analyzed the probability of OOPE for medicines, the share of total OOPE due to medicines out of total OOPE in health (reported as a ratio between zero and one), the OOPE amount for medicines reported (in United States Dollars), and the share of OOPE amount on medicines out of total household expenditure (reported as a ratio between zero and one). Predictors of analyzed outcomes were identified using three regression models. RESULTS: Out of those households who spent on healthcare, the probability of having any OOPE on medicines was 87.9%. Of those who spent on medicines, the median monthly expenditure was US$3.03. The poorest households spent 9.97% of their total household expenditure as OOPE on medicines, nearly double that of the wealthiest households (5.86%). The characteristic which showed the most significant correlation to a high OOPE on medicines was the presence of chronic diseases, especially cancer. Twenty six percent of all surveyed households spend more than 10% of their OOPE on medicines. CONCLUSIONS: Our study shows that financial protection should be targeted at the poorest quintiles and such protection should include enrollment of rural households. Further, outpatient medicines benefits should include those for non-communicable diseases (NCDs).
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Gastos em Saúde , Pobreza , Bangladesh , Estudos Transversais , Humanos , Inquéritos e QuestionáriosRESUMO
Background: Universal access to essential medicines and routine diagnostics is required to combat the growing burden of cardiovascular disease (CVD) and diabetes. Evaluating health systems and various access dimensions availability, affordability, accessibility, acceptability, and quality is crucial yet rarely performed, especially in low- and middle-income countries. Objective: To evaluate health system capacity and barriers in accessing diagnostics and essential medicines for CVD and diabetes in Nepal. Methods: We conducted a WHO/HAI nationally-representative survey in 45 health-facilities (public-sector: 11; private-sector: 34) in Nepal to collect availability and price data for 21 essential medicines for treating CVD and diabetes, during MayJuly 2017. Data for 13 routine diagnostics was obtained in 12 health facilities. Medicines were considered unaffordable if the lowest paid worker spends >1 days wage to purchase a monthly supply. To evaluate accessibility, we conducted facility exit interviews among 636 CVD patients. Accessibility (e.g., private-public health facility mix, travel to hospital/pharmacy) and acceptability (i.e. Nepals adoption of WHO Essential Medicine List, and patient medication adherence) were summarized using descriptive statistics, and we conducted a systematic review of relevant literature. We did not evaluate medicine quality. Results: We found that mean availability of generic medicines is low (<50%) in both public and private sectors, and less than one-third medicines met WHOs availability target (80%). Mean (SD) availability of diagnostics was 73.1% (26.8%). Essential medicines appear locally unaffordable. On average, the lowest-paid worker would spend 1.03 (public-sector) and 1.26 (private-sector) days wages to purchase a monthly supply. For a person undergoing CVD secondary preventive-interventions in the private sector, the associated expenditure would be 7.511.2% of monthly household income. Exit-interviews suggest that a long/expensive commute to health-facilities and poor medicine affordability constrain access. Conclusions: This study highlights critical gaps in Nepals health system capacity to offer basic health services to CVD and diabetes patients, owing to low availability, poor affordability and accessibility of essential medicines and diagnostics. Research and policy initiatives are needed to ensure uninterrupted supply of affordable essential medicines and diagnostics.
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Doenças Cardiovasculares , Diabetes Mellitus , Medicamentos Essenciais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Acessibilidade aos Serviços de Saúde , Humanos , NepalRESUMO
Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By comparison, less is known about pathogenic DNA variants in people from other parts of the world. Consequently, inclusion of currently underrepresented Indigenous and other minority population groups in genomic research is essential to enable equitable outcomes in ECS and other areas of genomic medicine. Here, we discuss this issue in relation to the implementation of ECS in Australia, which is currently being evaluated as part of the national Government's Genomics Health Futures Mission. We argue that significant effort is required to build an evidence base and genomic reference data so that ECS can bring significant clinical benefit for many Aboriginal and/or Torres Strait Islander Australians. These efforts are essential steps to achieving the Australian Government's objectives and its commitment "to leveraging the benefits of genomics in the health system for all Australians." They require culturally safe, community-led research and community involvement embedded within national health and medical genomics programs to ensure that new knowledge is integrated into medicine and health services in ways that address the specific and articulated cultural and health needs of Indigenous people. Until this occurs, people who do not have European ancestry are at risk of being, in relative terms, further disadvantaged.
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Metagenômica/métodos , Grupos Populacionais/genética , Austrália , Variação Genética/genética , HumanosRESUMO
Breast cancers display phenotypic and functional heterogeneity and several lines of evidence support the existence of cancer stem cells (CSCs) in certain breast cancers, a minor population of cells capable of tumor initiation and metastatic dissemination. Identifying factors that regulate the CSC phenotype is therefore important for developing strategies to treat metastatic disease. The Inhibitor of Differentiation Protein 1 (Id1) and its closely related family member Inhibitor of Differentiation 3 (Id3) (collectively termed Id) are expressed by a diversity of stem cells and are required for metastatic dissemination in experimental models of breast cancer. In this study, we show that ID1 is expressed in rare neoplastic cells within ER-negative breast cancers. To address the function of Id1 expressing cells within tumors, we developed independent murine models of Triple Negative Breast Cancer (TNBC) in which a genetic reporter permitted the prospective isolation of Id1+ cells. Id1+ cells are enriched for self-renewal in tumorsphere assays in vitro and for tumor initiation in vivo. Conversely, depletion of Id1 and Id3 in the 4T1 murine model of TNBC demonstrates that Id1/3 are required for cell proliferation and self-renewal in vitro, as well as primary tumor growth and metastatic colonization of the lung in vivo. Using combined bioinformatic analysis, we have defined a novel mechanism of Id protein function via negative regulation of the Roundabout Axon Guidance Receptor Homolog 1 (Robo1) leading to activation of a Myc transcriptional programme.
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BACKGROUND: Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC through unknown mechanisms. METHODS: Here, we have defined unique molecular insights into the function of ID4 in BLBC and the related disease high-grade serous ovarian cancer (HGSOC), by combining RIME proteomic analysis, ChIP-seq mapping of genomic binding sites and RNA-seq. RESULTS: These studies reveal novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins (γH2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage. Analysis of clinical samples demonstrates that ID4 is amplified and overexpressed at a higher frequency in BRCA1-mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair deficiency. CONCLUSIONS: These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOC.
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Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Proteínas Inibidoras de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/metabolismo , Animais , Apoptose/fisiologia , Neoplasias da Mama/patologia , Carcinoma Basocelular/patologia , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Cromatina/genética , Cromatina/metabolismo , Dano ao DNA , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Prognóstico , Proteogenômica , Células Tumorais CultivadasRESUMO
Acquired resistance to endocrine therapy is responsible for half of the therapeutic failures in the treatment of breast cancer. Recent findings have implicated increased expression of the ETS transcription factor ELF5 as a potential modulator of estrogen action and driver of endocrine resistance, and here we provide the first insight into the mechanisms by which ELF5 modulates estrogen sensitivity. Using chromatin immunoprecipitation sequencing we found that ELF5 binding overlapped with FOXA1 and ER at super enhancers, enhancers and promoters, and when elevated, caused FOXA1 and ER to bind to new regions of the genome, in a pattern that replicated the alterations to the ER/FOXA1 cistrome caused by the acquisition of resistance to endocrine therapy. RNA sequencing demonstrated that these changes altered estrogen-driven patterns of gene expression, the expression of ER transcription-complex members, and 6 genes known to be involved in driving the acquisition of endocrine resistance. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, and proximity ligation assays, we found that ELF5 interacted physically with members of the ER transcription complex, such as DNA-PKcs. We found 2 cases of endocrine-resistant brain metastases where ELF5 levels were greatly increased and ELF5 patterns of gene expression were enriched, compared to the matched primary tumour. Thus ELF5 alters ER-driven gene expression by modulating the ER/FOXA1 cistrome, by interacting with it, and by modulating the expression of members of the ER transcriptional complex, providing multiple mechanisms by which ELF5 can drive endocrine resistance.
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Neoplasias da Mama/genética , Proteínas de Ligação a DNA/metabolismo , Elementos Facilitadores Genéticos , Regulação Neoplásica da Expressão Gênica , Receptores de Estrogênio/metabolismo , Fatores de Transcrição/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Humanos , Células MCF-7 , Camundongos , Ligação ProteicaRESUMO
Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing.
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Bases de Dados Genéticas , Variação Genética , Genoma Humano , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Frequência do Gene , Predisposição Genética para Doença , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Neoplasias/genética , Desempenho Físico Funcional , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Affordability is a key barrier to access to medicines. Generic medicines policies can address this barrier and promote access. Successful uptake of generic medicines depends, in part, on ensuring that these products are interchangeable with reference products. Typically, bioequivalence certification is established in order to demonstrate such interchangeability. OBJECTIVE: To study the implementation of the bioequivalence certification policy in Chile. METHODS: We used Chilean Market Regulatory Authority data for analysis to study the number of products that obtained bioequivalence certification, the time until bioequivalence certification and associated factors to obtain bioequivalence. RESULTS: As of January 2017, out of 2,336 products with a valid market authorization containing at least one of the 167 APIs that required BE certification, 1,026 products actually have BE certification (1,026/2,336, 43.9% compliance). Where data were available, the time between submission of the market authorization as a bioequivalent product to final authorization by the national medicine regulatory authority for most products varied between 4-6 months. The fraction of all BE products containing a given API out of the total marketed products containing that API varies considerably, e.g. for the API olmesartan there was only a single BE product marketed, the API diclofenac had none. CONCLUSIONS: Although the implementation of Chile's bioequivalence policy increased the number of bioequivalent products, over 50% of generic products requiring bioequivalence that did not obtain this certification. Also for some of the API none or very few BE products are marketed which limits the success of a substitution policy. Further studies are required to identify the apparent lack of incentives to obtain bioequivalence certification. Studies of sales volumes and prices of the products are needed to identify whether generic products without bioequivalence certification either become bioequivalent or eventually exit the market.
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Medicamentos Genéricos/economia , Equivalência Terapêutica , Certificação/economia , Chile , Humanos , Políticas , Registros/economiaRESUMO
We compared antibiotic prescribing for children with and those without an underlying chronic condition associated with increased risk for invasive pneumococcal disease. Children with a chronic condition had significantly greater cumulative exposure to antibiotics and higher rates of prescriptions per person-year than those without a chronic condition; this population is at increased risk for the emergence of multidrug-resistant pathogens.
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Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Doença Crônica , Farmacorresistência Bacteriana Múltipla , Infecções Pneumocócicas/diagnóstico , Padrões de Prática Médica/estatística & dados numéricos , Criança , Pré-Escolar , Humanos , Prescrição Inadequada , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Infecções Pneumocócicas/microbiologia , Fatores de RiscoRESUMO
Allele frequency data from human reference populations is of increasing value for the filtering, interpretation, and assignment of pathogenicity to genetic variants. Aged and healthy populations are more likely to be selectively depleted of pathogenic alleles and therefore particularly suitable as a reference population for the major diseases of clinical and public health importance. However, reference studies of confirmed healthy elderly individuals have remained under-represented in human genetics. Here we describe the Medical Genome Reference Bank (MGRB), a large-scale comprehensive whole-genome data set of healthy elderly individuals. The MGRB provides an accessible data resource for health-related research and clinical genetics and a powerful platform for studying the genetics of healthy ageing. The MGRB is comprised of 4000 healthy, older individuals, mostly of European descent, recruited from two Australian community-based cohorts. Each participant lived ≥70 years with no reported history of cancer, cardiovascular disease, or dementia. DNA derived from blood samples has been subject to whole-genome sequencing. The MGRB has committed to a policy of data sharing, employing a hierarchical data management system to maintain participant privacy and confidentiality, while maximising research and clinical usage of the database. The MGRB represents a resource of international significance, which will be made broadly accessible to the clinical and genetic research community.
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Envelhecimento/genética , Bases de Dados Genéticas/normas , Genoma Humano , Idoso , Estudos de Coortes , Feminino , Voluntários Saudáveis , Humanos , Masculino , Sequenciamento Completo do Genoma/normasRESUMO
National Health Insurance (NHI) was implemented in Taiwan in 1995, and has significantly increased coverage to 99% of the population. The implementation of NHI has had large impacts on health disparities. Despite that, the NHI faces multiple challenges, including the condition of "coverage without access" among the Taiwanese aboriginal population, mostly residing in mountainous townships and experiencing lower socioeconomic status, decreased health outcomes, and limited access to adequate high-quality health care services. This paper summarizes the persistent health gap and the differences in health care utilization and health outcomes between the aboriginal population in rural townships and urban populations in Taiwan. Mountainous townships face challenges including lack of access to high-quality health care services and limited medical resources. Further policy recommendations and current progress are highlighted and discussed.
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Programas Nacionais de Saúde , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , População Rural/estatística & dados numéricos , Política de Saúde , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Programas Nacionais de Saúde/estatística & dados numéricos , Grupos Populacionais/estatística & dados numéricos , Serviços de Saúde Rural/estatística & dados numéricos , TaiwanRESUMO
BACKGROUND: We present a systematic review describing ex-ante and ex-post evaluations of the impacts of intellectual property provisions in trade treaties on access to medicine in low and middle income countries. These evaluations focused on multilateral and bilateral trade agreements. We ascertained which IP provisions impacting access to medicines were the focus of these evaluations. We provide a further research agenda related to investigating the effect of trade agreement's intellectual property provisions on access to medicines. We followed systematic review guidelines with 7 different databases to identify post-2000 ex ante and ex post evaluations of trade treaties on access to medicines in low and middle-income countries. We included only quantitative ex-ante studies that used structural modeling and simulations to derive quantitative predictions and ex-post studies that utilized empirical data and econometric techniques to quantify the effects of intellectual property provisions in free trade agreements on host country's pharmaceutical industry. The search strategy identified 744 titles after removal of duplicates. We identified 14 studies that fulfilled all eligibility; 7 studies are ex-ante and 7 are ex-post. The studies looked at medicine price and cost, affordability, welfare effects and speed of medicine market launch. Changes in intellectual property policy due to the implementation of trade agreements affect price, medicines expenditure and sales, consumer welfare, and ultimately the affordability, of medicines. The direction and magnitude of the price effects differ between ex-ante and ex-post studies. Further, the reported impacts of policy changes due to trade agreements on medicine access seem clearly multifactorial. CONCLUSION: Both ex ante and ex post methods have advantages and limitations and, on balance, both types report, for the most part, an increase in price and a decrease in consumer welfare with imposition of intellectual property protection in trade agreements. The main differences between these studies are in the magnitude of the changes. There is a gap in our empirical understanding of the mechanisms through which such changes affect access to medicines and which outcomes relevant to access are most affected by which type of changes in intellectual property policy and law.