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Background: This paper has set out to map the state of pharmaceutical regulation in the developing world through the construction of cross-national indices drawing from World Health Organization data. The last two decades have been characterized by deep changes for the pharmaceutical sector, including the complete transformation of intellectual property systems at the behest of the World Trade Organization and the consolidation of global active ingredient suppliers in China and India. Although the rules for ownership of medicine have been set and globally implemented, we know surprisingly little about how the standards for market entrance and regulation of pharmaceutical products have changed at the national level. How standardized are national pharmaceutical market systems? Do we find homogeneity or variation across the developing world? Are their patterns for understanding why some countries have moved closer to one global norm for pharmaceutical regulation and others have developed hybrid models for oversight of this sector? Access to medicine is a core tool in public health. This paper gauges the levels of standards in public and private generics markets for developing countries building on national-level pharmaceutical market surveys for 78 countries to offer three indicators of market oversight: State Regulatory Infrastructure, Monitoring the Private Market and Public Quality Control. Identifying the different variables that affect a state's institutional capacity and current standard level offers new insights to the state of pharmaceuticals in the developing world. It is notable that there are very few (none at the time of this paper) studies that map out the new global terrain for pharmaceutical regulation in the post-TRIPS context.Results: This paper uses item response theory to develop original indicators of pharmaceutical regulation. We find remarkable resistance to the implementation of global pharmaceutical norms for quality standards in developing states and in regulatory infrastructure. Human capacity across many developing countries remains limited. Most notably, variation among states is stark. Countries that have been leaders in establishing global norms do not appear to have influenced their neighbors in establishing regional patterns. Finally, in contrast to traditional theories of international norms diffusion, global standard-setters such as the United States or European Union appear to have surprisingly little influence on standard setting across our survey.Conclusions: Our research has implications for the framing of technical support on public health initiatives aimed at strengthening local public institutions in medicine and offers a new methodological approach for analyzing drug regulation systems in developing countries. [ABSTRACT FROM AUTHOR]

Background: Antibiotics have played an essential role in decreasing morbidity and mortality from infectious diseases. However, indiscriminate use and unrestricted access is contributing to the emergence of bacterial resistance. This paper reports on a situational analysis of antimicrobial use and resistance in Ghana, with focus on policy and regulation.Methods: Relevant policy documents, reports, regulations and enactments were reviewed. PubMed and Google search engines were used to extract relevant published papers. Websites of stakeholders such as Ministry of Health (MOH) and its agencies were also reviewed. An interview guide was used to elicit responses from selected officials from these sectors.Results: Laws and guidelines to control the use of antimicrobials in humans were available but not for animals. There was no National Antimicrobial Policy (NAP). A health practice regulatory law mandates Physicians, Physician Assistants, Midwives and trained Nurses to prescribe antimicrobials. However, antibiotics are widely prescribed and dispensed by unauthorised persons, suggesting weak enforcement of the laws. Antibiotics were also supplied to and from unapproved medicine outlets. The Standard Treatment Guidelines (STG), Essential Medicines List (EML) and the National Health Insurance Scheme Medicines List (NHISML) provide restrictions regarding levels of prescribing of antimicrobials. However, existing guidelines on antibiotic use are mostly not adhered to. The use of Automatic Stop Orders to avoid wastage in the hospitals is also not practiced. Data on use of antibiotics for individuals are not readily available in most facilities. Again, there are no standards or guidelines on veterinary use of antibiotics. Surveillance systems for consumption of antibiotics and resistance monitoring were not in place in most health facilities. However, there is an ongoing national action to create awareness on bacteria resistance, strengthening knowledge through research and surveillance and development of NAP in line with global action plan on antimicrobial resistance.Conclusion: Absence of national antimicrobial policy, weak regulatory environment and non-adherence to practice standards may have contributed to increased and unregulated access to antimicrobials in Ghana, a catalyst for development and spread of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background The heads of the Global Fund and the GAVI Alliance have recently promoted the idea of an international tiered pricing framework for medicines, despite objections from civil society groups who fear that this would reduce the leeway for compulsory licenses and generic competition. This paper explores the extent to which an international tiered pricing framework and the present leeway for compulsory licensing can be reconciled, using the perspective of the right to health as defined in international human rights law. Discussion We explore the practical feasibility of an international tiered pricing and compulsory licensing framework governed by the World Health Organization. We use two simple benchmarks to compare the relative affordability of medicines for governments -- average income and burden of disease -- to illustrate how voluntary tiered pricing practice fails to make medicines affordable enough for low and middle income countries (if compared with the financial burden of the same medicines for high income countries), and when and where international compulsory licenses should be issued in order to allow governments to comply with their obligations to realize the right to health. Summary An international tiered pricing and compulsory licensing framework based on average income and burden of disease could ease the tension between governments' human rights obligation to provide medicines and governments' trade obligation to comply with the Agreement on Trade-Related Aspects of Intellectual Property Rights. [ABSTRACT FROM AUTHOR]

Background: Rapidly evolving socioeconomic and technological trends make it challenging to improve access, effectiveness and efficiency in the use of pharmaceuticals. This paper identifies and systematically classifies the prevailing pharmaceutical policies worldwide in relation to a country's income status.Methods: A literature search was undertaken to identify and taxonomize prevailing policies worldwide. Countries that apply those policies and those that do not were then grouped by income status.Results: Pharmaceutical policies are linked to a country's socioeconomics. Developed countries have universal coverage and control pharmaceuticals with external and internal price referencing systems, and indirect price-cost controls; they carry out health technology assessments and demand utilization controls. Price-volume and risk-sharing agreements are also evolving. Developing countries are underperforming in terms of coverage and they rely mostly on restrictive state controls to regulate prices and expenditure.Conclusions: There are significant disparities worldwide in the access to pharmaceuticals, their use, and the reimbursement of costs. The challenge in high-income countries is to maintain access to care whilst dealing with trends in technology and aging. Essential drugs should be available to all; however, many low- and middle-income countries still provide most of their population with only poor access to medicines. As economies grow, there should be greater investment in pharmaceutical care, looking to the policies of high-income countries to increase efficiency. Pharmaceutical companies could also develop special access schemes with low prices to facilitate coverage in low-income countries. [ABSTRACT FROM AUTHOR]

Therapeutic use of an unauthorised drug (or of an authorised drug for an unauthorised indication) for patients with a life-threating disease is permitted outside a clinical trial as an Expanded Access Programme (EAP).The regulations regarding EAPs is not the same all over the world. For example, the recommendation of the European Medicines Agency (EMA) in EU countries also includes within EAPs patients who have been treated in a clinical trial and who wish to continue the treatment. Nevertheless, the patients treated in a clinical trial could have the option of continuing treatment for an extended period in an Open-label Extension study, aimed to generate long-term data on efficacy, safety, tolerability and administration.The aims of this paper - based on the difficulties and incoherence encountered by an Italian Ethic Committee (EC) during the authorisation process of EAPs - are: understanding the origin of this misclassification by analysing differences and similarities among USA, European and Italian regulations concerning EAPs; and showing difficulties in classifying international study protocols as a consequence of the lack of harmonisation of definitions.We performed a critical review of the current USA, European and Italian regulations and we analysed some practical cases by retrieving protocols from Clinicaltrials.gov and the Italian Clinical Trials Registry (OsSC) containing in the title the keywords 'Expanded Access Programme', "'Expanded Access', 'Open-label Extension study' or 'Early Access'.We observed that the Food and Drug Administration ( FDA) definition of EAP is very clear while the EMA definition is similar to that of an Open-label Extension study. This lack of a clear definition generates misclassification and it is possible to find an EAP with an efficacy or safety endpoint; or an EAP managed as a clinical trial; or an EAP classified in Clinical Trials Registries as a phase II, III or IV clinical trial.The internationalisation of the studies requires a harmonisation on a global level of legislation and definitions to eliminate misclassification of protocols. For this reason, the authors suggest that: a) the EMA definition should be harmonised with the FDA definition of EAPs, b) European regulation, even if optional, should be adopted in a compulsory way by national regulations. Moreover, separate registries for both EAPs and clinical trials should be organised. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship programs (ASPs) have been shown to reduce inappropriate antimicrobial use and its consequences. However, these programs lack legislative requirements in many places and it can be difficult to determine what human resources are required for these programs and how to create a business case to present to hospital administrators for program funding. The objectives of the current paper were to review legislative requirements and outline human resource requirements for ASPs, and to create a base business case for ASPs. Methods: A working group of antimicrobial stewardship experts from across Canada met to discuss the necessary components for creation of a business case for antimicrobial stewardship. A narrative review of the literature of the regulatory requirements and human resource recommendations for ASPs was conducted. Informed by the review and using a consensus decision-making process, the expert working group developed human resource recommendations based on a 1000 bed acute care health care facility in Canada. A spreadsheet based business case model for ASPs was also created. Results: Legislative and /or regulatory requirements for ASPs were found in 2 countries and one state jurisdiction. The literature review and consensus development process recommended the following minimum human resources complement: 1 physician, 3 pharmacists, 0.5 program administrative and coordination support, and 0.4 data analyst support as full time equivalents (FTEs) per 1000 acute care beds. Necessary components for the business case model, including the human resource requirements, were determined to create a spreadsheet based model. Conclusions: There is evidence to support the negative outcomes of inappropriate antimicrobial use as well as the benefits of ASPs. Legislative and /or regulatory requirements for ASPs are not common. The available evidence for human resource recommendations for ASPs using a narrative review process was examined and a base business case modelling scenario was created. As regulatory requirements for ASPs increase, it will be necessary to create accurate business cases for ASPs in order to obtain the necessary funding to render these programs successful. [ABSTRACT FROM AUTHOR]

Background: Over the past several decades, there have been numerous peer-reviewed articles written about people who use drugs (PWUDs) from the Downtown Eastside neighborhood of Vancouver, Canada. While individual researchers have engaged and acknowledged this population as participants and community partners in their work, there has been comparatively little attention given to the role of PWUDs and drug user organizations in directing, influencing, and shaping research agendas.Methods: In this community-driven research, we examine 20 years of peer-reviewed studies, university theses, books, and reports that have been directed, influenced, and shaped by members of the activist organization the Vancouver Area Network of Drug Users (VANDU). In this paper, we have summarized VANDU's work based on different themes from each article.Results: After applying the inclusion criteria to over 400 articles, 59 items containing peer-reviewed studies, books, and reports were included and three themes of topics researched or discussed were identified. Theme 1: 'health needs' of marginalized groups was found in 39% of articles, Theme 2: 'evaluation of projects' related to harm reduction in 19%, and Theme 3: 'activism' related work in 42%. Ninety-four percent of co-authors were from British Columbia and 44% of research was qualitative. Works that have been co-authored by VANDU's members or acknowledged their participations created 628 citations. Moreover, their work has been accessed more than 149,600 times.Conclusions: Peer-based, democratic harm reduction organizations are important partners in facilitating groundbreaking health and social research, and through research can advocate for the improved health and wellbeing of PWUDs and other marginalized groups in their community. This article also recommends that PWUDs should be more respectfully engaged and given appropriate credit for their contributions. [ABSTRACT FROM AUTHOR]

Chinese herbal medicines (CHMs) have unique advantages in the prevention and treatment of diseases, which are widely recognized in the world. More and more CHMs are becoming increasingly popular in the international markets. However, the quality control of CHMs is a significant issue for their acceptance and recognition in the international market. This review mainly focuses on the quality requirements for CHMs to enter the European Union (EU) market. Both Chinese and European regulations and quality controls are compared. Firstly, the EU medicinal regulatory system and relevant regulations were reviewed. Secondly, the key factors of the quality control of CHMs, including Chinese herbal drugs, extracts and products were compared with those of European herbal medicines in the EU market. Subsequently, three main registration routes for herbal medicinal products including Chinese herbal medicinal products entering the EU were introduced. Furthermore, the legal status of traditional Chinese medicine granules in the EU was also discussed. Through the comparison of the key quality factors for CHMs in China and the EU, the similarities and differences in terms of quality requirements and regulations are addressed, which provides a reference for the development of CHMs into the EU market. [ABSTRACT FROM AUTHOR]

Objective: Substandard and falsified (SF) medical products are a global public health threat. The presence and spread of SF drugs negatively affect (1) patients' safety and health outcomes, (2) national economy, (3) public trust in the healthcare system, and (4) the international fight against serious health challenges such as malaria and antimicrobial resistance. The objective of the current study was to investigate and provide a snapshot analysis of the evolution and developmental patterns of global research publications on SF products.Methods: A bibliometric approach was adopted using terms such as fake, falsified, counterfeit, substandard, and others. No language restriction was made. The study period was from 1900 up to 2020. The search strategy was validated and implemented using Scopus database.Results: The search strategy retrieved 978 documents authored by 2861 researchers from 100 different countries and published in 421 different journals. The retrieved documents received 11,237 citations (11.5 citations per document) with an H-index of 53. The 978 documents retrieved from Scopus were published from 1961 to 2020, giving an average of 16.6 publications per year. The present study indicated that research on SF medical products: (a) has experienced a steep growth from 2001 to 2012 followed by a steady-state growth; (b) was disseminated in a wide range of journals, mainly in the fields of the pharmaceutical industry, analytical chemistry, public health, infectious diseases, and internal medicine; (c) was published by scholars with diverse and distant geographical backgrounds; (d) was mainly produced in the United States, United Kingdom, and Germany; (d) has fragmented research networks and a limited number of researchers per network; (e) has limited cross-country collaboration except for that between the US and the UK in one hand and countries in the Mekong region in the other hand; (f) emphasized on medications related to malaria and sexual stimulants; and (g) received relatively inadequate funding.Conclusions: Research on SF medical products is important and should remain a priority to ensure good quality of medications. Research activity in the field needs to be encouraged in world regions such as Africa and the Middle East where drug regulations are unsatisfactory and cross-border trade of illegal medications is common. [ABSTRACT FROM AUTHOR]

Background: The National Medical Products Administration (NMPA) in China has set to advance the regulatory capacity of traditional Chinese medicines (TCMs) with the adoption of regulatory science (RS). However, the priority of actions at the interface of RS and TCMs were yet to be defined. This research aims to identify the priority areas and summarize core actions for advancing RS for traditional medicines in China. Methods: A mixed approach of documentary analysis of government policies, regulations and official information about TCMs regulation in China, and a scoping review of literature using 4 databases (PubMed, ScienceDirect, Scopus and CNKI) on major concerns in TCMs regulation was employed. Results: Ten priority areas in the development of TCM-related regulatory science in China have been identified, including: (1) modernizing the regulatory system with a holistic approach; (2) advancing the methodology for the quality control of TCMs; (3) fostering the control mechanism of TCMs manufacturing process; (4) improving clinical evaluation of TCMs and leveraging real world data; (5) re-evaluation of TCMs injection; (6) developing evaluation standards for classic TCMs formula; (7) harnessing diverse data to improve pharmacovigilance of TCMs; (8) evaluating the value of integrative medicine in clinical practice with scientific research; (9) advancing the regulatory capacity to encourage innovation in TCMs; and (10) advancing a vision of collaboration for RS development in TCMs. Conclusions: RS for TCMs in China encompasses revolution of operational procedures, advancement in science and technology, and cross-disciplinary collaborations. Such experiences could be integrated in the communications among drug regulatory authorities to promote standardized and scientific regulation of traditional medicines. [ABSTRACT FROM AUTHOR]

Background: Whilst many studies have linked increased drug and cannabis exposure to adverse mental health (MH) outcomes their effects on whole populations and geotemporospatial relationships are not well understood.Methods: Ecological cohort study of National Survey of Drug Use and Health (NSDUH) geographically-linked substate-shapefiles 2010-2012 and 2014-2016 supplemented by five-year US American Community Survey. Drugs: cigarettes, alcohol abuse, last-month cannabis use and last-year cocaine use. MH: any mental illness, major depressive illness, serious mental illness and suicidal thinking.Data Analysis: two-stage, geotemporospatial, robust generalized linear regression and causal inference methods in R.Results: 410,138 NSDUH respondents. Average response rate 76.7%. When drug and sociodemographic variables were combined in geospatial models significant terms including tobacco, alcohol, cannabis exposure and various ethnicities remained in final models for all four major mental health outcomes. Interactive terms including cannabis were related to any mental illness (β-estimate = 1.97 (95%C.I. 1.56-2.37), P <  2.2 × 10- 16), major depressive episode (β-estimate = 2.03 (1.54-2.52), P = 3.6 × 10- 16), serious mental illness (SMI, β-estimate = 2.04 (1.48-2.60), P = 1.0 × 10- 12), suicidal ideation (β-estimate = 1.99 (1.52-2.47), P <  2.2 × 10- 16) and in each case cannabis alone was significantly associated (from β-estimate = - 3.43 (- 4.46 - -2.42), P = 3.4 × 10- 11) with adverse MH outcomes on complex interactive regression surfaces. Geospatial modelling showed a monotonic upward trajectory of SMI which doubled (3.62 to 7.06%) as cannabis use increased. Extrapolated to whole populations cannabis decriminalization (4.26%, (4.18, 4.34%)), Prevalence Ratio (PR) = 1.035(1.034-1.036), attributable fraction in the exposed (AFE) = 3.28%(3.18-3.37%), P < 10- 300) and legalization (4.75% (4.65, 4.84%), PR = 1.155 (1.153-1.158), AFE = 12.91% (12.72-13.10%), P < 10- 300) were associated with increased SMI vs. illegal status (4.26, (4.18-4.33%)).Conclusions: Data show all four indices of mental ill-health track cannabis exposure across space and time and are robust to multivariable adjustment for ethnicity, socioeconomics and other drug use. MH deteriorated with cannabis legalization. Cannabis use-MH data are consistent with causal relationships in the forward direction and include dose-response and temporal-sequential relationships. Together with similar international reports and numerous mechanistic studies preventative action to reduce cannabis use is indicated. [ABSTRACT FROM AUTHOR]

Background: Choice of minimum legal age (MLA) for cannabis use is a critical and contentious issue in legalization of non-medical cannabis. In Canada where non-medical cannabis was recently legalized in October 2018, the federal government recommended age 18, the medical community argued for 21 or even 25, while public consultations led most Canadian provinces to adopt age 19. However, no research has compared later life outcomes of first using cannabis at these different ages to assess their merits as MLAs.Methods: We used doubly robust regression techniques and data from nationally representative Canadian surveys to compare educational attainment, cigarette smoking, self-reported general and mental health associated with different ages of first cannabis use.Results: We found different MLAs for different outcomes: 21 for educational attainment, 19 for cigarette smoking and mental health and 18 for general health. Assuming equal weight for these individual outcomes, the 'overall' MLA for cannabis use was estimated to be 19 years. Our results were robust to various robustness checks.Conclusion: Our study indicated that there is merit in setting 19 years as MLA for non-medical cannabis. [ABSTRACT FROM AUTHOR]

Background: Marijuana is the most commonly used illicit drug in the United States. More and more states legalized medical and recreational marijuana use. Adolescents and emerging adults are at high risk for marijuana use. This ecological study aims to examine historical trends in marijuana use among youth along with marijuana legalization.Method: Data (n = 749,152) were from the 31-wave National Survey on Drug Use and Health (NSDUH), 1979-2016. Current marijuana use, if use marijuana in the past 30 days, was used as outcome variable. Age was measured as the chronological age self-reported by the participants, period was the year when the survey was conducted, and cohort was estimated as period subtracted age. Rate of current marijuana use was decomposed into independent age, period and cohort effects using the hierarchical age-period-cohort (HAPC) model.Results: After controlling for age, cohort and other covariates, the estimated period effect indicated declines in marijuana use in 1979-1992 and 2001-2006, and increases in 1992-2001 and 2006-2016. The period effect was positively and significantly associated with the proportion of people covered by Medical Marijuana Laws (MML) (correlation coefficients: 0.89 for total sample, 0.81 for males and 0.93 for females, all three p values < 0.01), but was not significantly associated with the Recreational Marijuana Laws (RML). The estimated cohort effect showed a historical decline in marijuana use in those who were born in 1954-1972, a sudden increase in 1972-1984, followed by a decline in 1984-2003.Conclusion: The model derived trends in marijuana use were coincident with the laws and regulations on marijuana and other drugs in the United States since the 1950s. With more states legalizing marijuana use in the United States, emphasizing responsible use would be essential to protect youth from using marijuana. [ABSTRACT FROM AUTHOR]

Rare diseases collectively exert a global public health burden in the severity of their manifestations and the total number of people they afflict. For many patients, considerable barriers exist in terms of access to appropriate care, delayed diagnosis and limited or non-existing treatment options. Motivated by these challenges, the rare disease patient community has played a critical role, elevating the patient voice and mobilizing legislation to support the development of programs that address the needs of patients with rare diseases.The US Orphan Drug Act of 1983 served as a key milestone in this journey, providing a roadmap for other countries to introduce and implement similar orphan drug legislation; more recently, the European Union (EU) has gone further to encourage the widespread adoption and implementation of rare disease plans or strategies designed to more adequately address the comprehensive needs of patients with rare diseases. Despite these legislative efforts and the growing contributions of patient advocacy groups in moving forward implementation and adoption of rare disease programs, gaps still exist across the policy landscape for several countries. To gain deeper insights into the challenges and opportunities to address key needs of rare disease patients, it is critical to define the current status of rare disease legislation and policy across a geographically and economically diverse selection of countries. We analyzed the rare disease policy landscape across 11 countries: Germany, France, the United Kingdom, Canada, Bulgaria, Turkey, Argentina, Mexico, Brazil, China, and Taiwan. The status and implementation of policy was evaluated for each country in the context of key patient needs across 5 dimensions: improving coordination of care, diagnostic resources, access to treatments, patient awareness and support, and promoting innovative research. Our findings highlight the continuing role of the patient community in driving the establishment and adoption of legislation and programs to improve rare disease care. Further, we found that while national rare disease plans provide important guidance for improving care, implementation of plans is uneven across countries. More research is needed to demonstrate the effect of specific elements of rare disease plans on patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Policymakers and researchers frequently compare the prices of medicines between countries. Such comparisons often serve as barometers of how pricing and reimbursement policies are performing. The aim of this study was to examine methodological challenges to comparing generic drug prices.Methods: We calculated all commonly used price indices based on 2013 IMS Health data on sales of 3156 generic drugs in seven European countries.Results: There were large differences in generic drug prices between countries. However, the results varied depending on the choice of index, base country, unit of volume, method of currency conversion, and therapeutic category. The results also differed depending on whether one looked at the prices charged by manufacturers or those charged by pharmacists.Conclusions: Price indices are a useful statistical approach for comparing drug prices across countries, but researchers and policymakers should interpret price indices with caution given their limitations. Price-index results are highly sensitive to the choice of method and sample. More research is needed to determine the drivers of price differences between countries. The data suggest that some governments should aim to reduce distribution costs for generic drugs. [ABSTRACT FROM AUTHOR]

Background: Syndemics of illicit drug use and HIV remain as significant public health issues around the world. There has been increasing concern regarding the rapidly growing market of new psychoactive substances, particularly in Asia. In response, the Japanese government has increasingly banned such substances in recent years. We sought to identify the prevalence and correlates of use of quasi-legal psychoactive substances among people living with HIV/AIDS (PLHIV) in Japan.Methods: Data were derived from a nationwide survey of PLHIV conducted at nine leading HIV/AIDS care hospitals between July and December 2013. The prevalence and correlates of the use of quasi-legal psychoactive substances (e.g., synthetic cannabinoids, cathinone derivatives, etc. that had not been prohibited from using at the time of survey) among male participants were examined using multivariate survey logistic regression.Results: Among 963 study participants, the majority (95.3%) were male. The most commonly used drug among men was quasi-legal psychoactive substances (55.3% ever and 12.8% in the previous year). In multivariate analysis, the lifetime use of tryptamine-type derivatives (i.e., 5-MeO-DIPT or N,N-diisopropyl-5-methoxytryptamine) (adjusted odds ratio [AOR]: 2.42; 95% confidence interval [CI]: 1.36-4.28) and methamphetamine/amphetamine (AOR: 3.59; 95% CI: 2.13-6.04) were independently associated with recent quasi-legal psychoactive substance use.Conclusions: In our sample of male PLHIV in Japan, quasi-legal psychoactive substances were the most commonly used drugs. Individuals who had ever used tryptamine-type derivatives or methamphetamine/amphetamine were more likely to report recent quasi-legal psychoactive substance use, suggesting a potential shift in drug use patterns from regulated to unregulated substances among this population. These findings indicate a need for further research to examine implications for HIV care. [ABSTRACT FROM AUTHOR]

Background: More than 6,800 rare diseases and conditions have been identified in the US, which affect 25-30 million Americans. In 1983, the US Congress enacted the Orphan Drug Act (ODA) to encourage the development and marketing of drugs to treat rare diseases and conditions. This study analyzed all orphan designations and FDA approvals since 1983 through 2015, discussed the effectiveness of incentives for the development of treatments for rare diseases, and reflected on the ethical imperatives for timely access to orphan drugs.Methods: Study data were derived from the Food and Drug Administration (FDA) Orange Book and the Office of Orphan Drugs Development. A search was conducted to assess literature on the ethical principles and economic incentives for the development of orphan drugs.Results: In the period 1983-2015, the FDA granted 3,647 orphan drug designations and 554 orphan drug approvals. The orphan drug approvals corresponded to 438 different brand names. Cancer was the therapeutic area with the highest number of approvals. The increased number of patients with rare diseases and the growth in the cost of orphan drugs pose a significant economic burden for patients, public programs and private third party payers. Regulatory differences to qualify for orphan designation and various population thresholds employed by the FDA and the European Medicines Agency lead to further unmet health needs for patients with rare diseases and aggravate health inequities. There is no societal consensus on the population and economic thresholds, the drug effectiveness indicator(s), or the societal value to be placed for the approval and reimbursement of orphan drugs.Conclusion: Orphan drug development and marketing in the US concentrate in few therapeutic areas. Despite the increase in the number of FDA approved orphan drugs, the unmet needs of patients with rare diseases evidence that the current incentives are not efficiently stimulating orphan drug development. There is need to balance economic incentives to stimulate the development and marketing of orphan drugs without jeopardizing patients' access to treatment. Thus, aligning pharmaceutical companies' incentives with societal budgetary constraints is necessary and the ethical imperatives of timely access to orphan drugs need to be agreed upon. [ABSTRACT FROM AUTHOR]

Background: The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. Methods: Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. Results and discussion: A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84 % of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74 % of prescribers and 84 % of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. Conclusion: The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic medicines. [ABSTRACT FROM AUTHOR]

Background: Decentralization of ART services scaled up significantly with the country wide roll out of option B plus in Uganda. Little work has been undertaken to examine population level access to HIV care particularly in hard to reach areas in rural Africa. Most work on ART scale up has been done at health facility level which omits people not accessing healthcare in the community. This study describes health service usage, particularly HIV testing and care in 2/6 parishes of Lapono sub-county of northern Uganda, prior to introduction of ART services in Lira Kato Health Centre (a local lower-level health centre III), as part of ART decentralization.Methods: Household and individual questionnaires were administered to household members (aged 15-59 years). Logit random effects models were used to test for differences in proportions (allowing for clustering within villages).Results: 2124 adults from 1351 households were interviewed (755 [36%] males, 1369 [64 %] females). 2051 (97%) participants reported seeking care locally for fever, most on foot and over half at Lira Kato Health Centre. 574 (76%) men and 1156 (84%) women reported ever-testing for HIV (P < 0.001 for difference); 34/574 (6%) men and 102/1156 (9%) women reported testing positive (P = 0.04). 818/850 (96%) women who had given birth in the last 5 years had attended antenatal care in their last pregnancy: 7 women were already diagnosed with HIV (3 on ART) and 790 (97%) reported being tested for HIV (34 tested newly positive). 124/136 (91%) HIV-positive adults were in HIV-care, 123/136 (90 %) were taking cotrimoxazole and 74/136 (54%) were on ART. Of adults in HIV-care, most were seen at Kalongo hospital (n = 87), Patongo Health Centre (n = 7) or Lira Kato Health Centre (n = 23; no ART services). 58/87, 5/7 and 20/23 individuals walked to Kalongo hospital (56 km round-trip, District Health Office information), Patongo Health Centre (76 km round-trip, District Health Office information) and Lira Kato Health Centre (local) respectively. 8 HIV-infected children were reported; only 2 were diagnosed aged <24 months: 7/8 were in HIV-care including 3 on ART.Conclusions: Higher proportions of women compared to men reported ever-testing for HIV and testing HIV-positive, similar to other surveys. HIV-infected men and women travelled considerable distances for ART services. Children appeared to be under-accessing testing and referral for treatment. Decentralization of ART services to a local health facility would decrease travel time and transport costs, making care and treatment more easily accessible. [ABSTRACT FROM AUTHOR]

Background: Sustainability and the ability to maintain the right to health, with the guarantee of access to quality medicines and health services, have been a great challenge for countries with universal health systems. The great technological advances bring with it an expressive increase in the expenditures of the health systems, especially those directed towards the acquisition of high-cost drugs, which are still under patent protection, have a high cost and, in some cases, present uncertainties about their effectiveness and safety. As a way of maintaining the proper functioning of the systems and guaranteeing access to these medicines, some countries started to negotiate discounts with manufacturing companies. Pricing agreements have been adopted by developed countries with the objective of reducing their spending on high-cost medicines and, although they represent an opportunity for better negotiation with the industries, they violate the principle of transparency that regulates the world market. However, the existence of confidentiality agreements has meant that the declared prices are not the actual prices, unfairly harming the countries that use these price lists as beacons in their systems. Methods: Representatives of health, judicial, legislative, patient organizations and academics from eight countries in Latin America and South Korea participated in a meeting in September 2017 in Chile to discuss price confidentiality agreements and the impact on public health policies. During the meeting, participants were presented with a hypothetical case to subsidize the discussion on the topic. Divided into groups, participants should propose recommendations for the problem by pointing out the pros and cons if each proposed recommendation was adopted. The groups were then confronted by a simulated jury and finally issued a single and final recommendation for the problem. Results: The topic was widely discussed and recommendations were raised by the participants. Among them, it is worth noting the elaboration of norms that regulate the negotiations of prices between the countries bringing transparency and harmony in the adopted conducts. In addition, the possible consequences and potential impacts of confidentiality on drug prices and inputs, such as information asymmetry and inequity of access between countries, were pointed out. Conclusion: Despite there are efforts to make price negotiations more transparent, there is still no well-established standardization that promotes a well-functioning market. Confidentiality agreements hamper the fairness of access to essential health products. [ABSTRACT FROM AUTHOR]

Background: In response to widespread opioid misuse, ten U.S. states have implemented regulations for facilities that primarily manage and treat chronic pain, called "pain clinics." Whether a clinic falls into a state's pain clinic definition determines the extent to which it is subject to oversight. It is unclear whether state pain clinic definitions model those found in the medical literature, and potential differences lead to discrepancies between scientific and professionally guided advice found in the medical literature and actual pain clinic practice. Identifying discrepancies could assist states to design laws that are more compatible with best practices suggested in the medical literature.Methods: We conducted an integrative systematic review to create a taxonomy of pain clinic definitions using academic medical literature. We then identified existing U.S. state pain clinic statutes and regulations and compared the developed taxonomy using a content analysis approach to understand the extent to which medical literature definitions are reflected in state policy.Results: In the medical literature, we identified eight categories of pain clinic definitions: 1) patient case mix; 2) single-modality treatment; 3) multidisciplinary treatment; 4) interdisciplinary treatment; 5) provider supervision; 6) provider composition; 7) marketing; and 8) outcome. We identified ten states with pain clinic laws. State laws primarily include the following definitional categories: patient case mix; single-modality treatment, and marketing. Some definitional categories commonly found in the medical literature, such as multidisciplinary treatment and interdisciplinary treatment, rarely appear in state law definitions.Conclusions: This is the first study to our knowledge to develop a taxonomy of pain clinic definitions and to identify differences between pain clinic definitions in U.S. state law and medical literature. Future work should explore the impact of different legal pain clinic definitions on provider decision-making and state-level health outcomes. [ABSTRACT FROM AUTHOR]