Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain.

Even though the early reports from China provided advance warning of what was to come, the COVID-19 pandemic has spread throughout the world with devastating consequences. Emergency measures are being implemented to reduce the magnitude of the public health crisis, prevent healthcare facilities from becoming overwhelmed and reduce the death toll of the disease. Containment strategies to mitigate viral transmission and emergency measures to increase the capacity of each country to provide intensive care are at the forefront of the public health management of the epidemic, even though the detrimental social and psychological effects of quarantine are evident on a global scale. Optimal management of critically ill patients with COVID-19 is also unclear, and the initial suggestion for early intubation as in typical ARDS may have caused significant harm. The management of mild cases of confirmed infection is another point of controversy, as drugs which may be repurposed for COVID-19 treatment have significant, potentially irreversible toxic effects and their use in mild cases of a viral illness which is typically self-limited may be harmful.

In and Beyond COVID-19: US Academic Pharmaceutical Science and Engineering Community Must Engage to Meet Critical National Needs.

The supply of affordable, high-quality pharmaceuticals to US patients has been on a critical path for decades. In and beyond the COVID-19 pandemic, this critical path has become tortuous. To regain reliability, reshoring of the pharmaceutical supply chain to the USA is now a vital national security need. Reshoring the pharmaceutical supply with old know-how and outdated technologies that cause inherent unpredictability and adverse environmental impact will neither provide the security we seek nor will it be competitive and affordable. The challenge at hand is complex akin to redesigning systems, including corporate and public research and development, manufacturing, regulatory, and education ones. The US academic community must be engaged in progressing solutions needed to counter emergencies in the COVID-19 pandemic and in building new methods to reshore the pharmaceutical supply chain beyond the pandemic.

[Ebola : an uncontrolled outbreak despite vaccines and new treatments]. / Ebola : vaccin et traitements efficaces mais épidémie persistante.

The Ebola virus disease outbreak raging in the North-Kivu and Ituri provinces of Democratic Republic of the Congo already accounts for more than 3400 cases, from which 2200 died. Major progress have been achieved since the 2014-2016 West Africa outbreak. A vaccine is now approved by the European Medicine Agency and has been administered to more than 250 000 volunteers in the field. New specific antiviral treatments are now available. Ebola virus disease shifted from a deadly disease to a preventable, curable one. However, the long-lasting conflict and repeated attacks of civilians and health workers hampers the control of the outbreak.

L'épidémie de maladie à virus Ebola (MVE) qui sévit dans les provinces du Nord-Kivu et de l'Ituri en République démocratique du Congo dans le nord-est du pays a déjà touché plus de 3400 personnes dont plus de 2200 sont décédées. Depuis la grande épidémie d'Afrique de l'Ouest en 2014-2016, d'énormes progrès ont été faits en termes de prise en charge et de prévention de la maladie. Il existe maintenant un vaccin homologué en Europe et d'autres sont en développement. L'efficacité des traitements spécifiques permet de modifier le devenir des patients infectés. De mortelle, la MVE est devenue évitable et guérissable. L'insé- curité de la région, zone de conflit depuis plus de 30 ans, rend cependant le contrôle de l'épidémie difficile.

100 Years of Medical Countermeasures and Pandemic Influenza Preparedness.

The 1918 influenza pandemic spread rapidly around the globe, leading to high mortality and social disruption. The countermeasures available to mitigate the pandemic were limited and relied on nonpharmaceutical interventions. Over the past 100 years, improvements in medical care, influenza vaccines, antiviral medications, community mitigation efforts, diagnosis, and communications have improved pandemic response. A number of gaps remain, including vaccines that are more rapidly manufactured, antiviral drugs that are more effective and available, and better respiratory protective devices.

Pharmaceutical lobbying and pandemic stockpiling of Tamiflu: a qualitative study of arguments and tactics.

Background: Little is known about how pharmaceutical companies lobby authorities or experts regarding procurement or the use of vaccines and antivirals. This paper investigates how members of Denmark's pandemic planning committee experienced lobbying efforts by Roche, manufacturer of Tamiflu, the antiviral that was stockpiled before the 2009 A(H1N1) pandemic. Methods: Analysis of interviews with six of seven members of the Danish core pandemic committee, supplemented with documentary analysis. We sought to identify (1) arguments and (2) tactics used in lobbying, and to characterize interviewees' views on the impact of (3) lobbying and (4) scientific evidence on the decision to stockpile Tamiflu. Results: Roche lobbied directly (in its own name) and through a seemingly independent third party. Roche used two arguments: (1) the procurement agreement had to be signed quickly because the drug would be delivered on a first-come, first-served basis and (2) Denmark was especially vulnerable to an influenza crisis because it had smaller Tamiflu stocks than other countries. Most interviewees suspected that lobbying had an impact on Tamiflu procurement. Conclusions: Our study highlights risks posed by pharmaceutical lobbying. Arguments and tactics deployed by Roche are likely to be repeated whenever many countries are negotiating drug procurements in a monopolistic market.

Direct Acting Antivirals Improve HCV Treatment Initiation and Adherence Among Underserved African Americans.

INTRODUCTION AND AIM: Adherence to hepatitis C (HCV) care was suboptimal in the interferon era among underserved African Americans (AA), but adherence data in the era of direct acting antivirals (DAA) is lacking in this population. We aimed to evaluate the impact of DAA on HCV care in underserved AA. MATERIAL AND METHODS: Clinical records of AAs undergoing HCV evaluation attending a safety net health system liver clinic were reviewed from 2006 to 2011 (pre-DAA), and January 1, 2014 to December 31, 2016 (post-DAA). RESULTS: 291 patients were identified (129 pre-DAA, and 162 post-DAA). Median age was 58, 66% were male, 91% had HCV genotype 1, and 70% had fibrosis ≥ stage 2. Post-DAA patients were older (60 vs. 53 years; p < 0.001), had higher rates of insurance (98 vs. 88%; p < 0.001), liver fibrosis ≥ stage 2 (77 vs. 61%; p = 0.048), ≥ 2 medical comorbidities (19 vs. 0.8%; p < 0.001), and median baseline log10 HCV RNA (6.07 vs. 5.81 IU/mL; p < 0.001), but lower median ALT (46 vs. 62 U/L; p < 0.001). Post-DAA, fewer patients were treatment ineligible (5.6 vs. 39%; p < 0.001) and more initiated therapy (71 vs. 8.5%; < 0.001), were adherent to HCV care (82 vs. 38%; p < 0.001), and achieved cure (95.7 vs. 63.6%, p < 0.001). Availability of DAA was independently associated with improved adherence to HCV care (OR 10.3, 95% CI 4.84-22.0). CONCLUSION: Availability of DAA is associated with increased treatment eligibility, initiation, adherence to HCV care, and cure in HCV-infected underserved AAs; highlighting the critical role of access to DAA in this population.

Is elimination of hepatitis C from the UK by 2030 a realistic goal?

Introduction: Highly effective, combination therapy for chronic hepatitis C virus (HCV) infection is now available. Current cure rates are close to 100% and applicable to all patients irrespective of race, age, severity of liver disease or viral genotype. Remarkably for persistent infection, current treatment is recommended for as little as 12 weeks; recent studies suggest even shorter courses. In contrast to interferon-based therapy, present regimens have few side effects and serious adverse events are rare. The success and safety of these regimens has stimulated interest in the possible eventual elimination of HCV. Barriers to elimination include cost of drugs and finding patients in the community less likely to interact with medical services who are a potential reservoir of infection. Sources of data: Pubmed. Areas of agreement: Antiviral agents already available are highly effective. Areas of controversy: The cost of the newer antiviral agents is very high, restricting treatment numbers in the UK in 2015/16 and focusing therapy on those patients with significant fibrosis. Recently, patients with less severe disease have been offered therapy, but delivery may be slowed by high costs. Many believe that insufficient pressure has been brought to bear to reduce costs. Eventual elimination will depend first on reducing treatment costs for those known to have chronic HCV infection and then finding patients in the community with infection unaware of their illness or reluctant/unable to engage with medical services. Areas for developing research: Determining the most effective strategies to identify 'invisible' patients in the community with chronic HCV infection.

Value for Money in H1N1 Influenza: A Systematic Review of the Cost-Effectiveness of Pandemic Interventions.

BACKGROUND: The 2009 A/H1N1 influenza pandemic generated additional data and triggered new studies that opened debate over the optimal strategy for handling a pandemic. The lessons-learned documents from the World Health Organization show the need for a cost estimation of the pandemic response during the risk-assessment phase. Several years after the crisis, what conclusions can we draw from this field of research? OBJECTIVE: The main objective of this article was to provide an analysis of the studies that present cost-effectiveness or cost-benefit analyses for A/H1N1 pandemic interventions since 2009 and to identify which measures seem most cost-effective. METHODS: We reviewed 18 academic articles that provide cost-effectiveness or cost-benefit analyses for A/H1N1 pandemic interventions since 2009. Our review converts the studies' results into a cost-utility measure (cost per disability-adjusted life-year or quality-adjusted life-year) and presents the contexts of severity and fatality. RESULTS: The existing studies suggest that hospital quarantine, vaccination, and usage of the antiviral stockpile are highly cost-effective, even for mild pandemics. However, school closures, antiviral treatments, and social distancing may not qualify as efficient measures, for a virus like 2009's H1N1 and a willingness-to-pay threshold of $45,000 per disability-adjusted life-year. Such interventions may become cost-effective for severe crises. CONCLUSIONS: This study helps to shed light on the cost-utility of various interventions, and may support decision making, among other criteria, for future pandemics. Nonetheless, one should consider these results carefully, considering these may not apply to a specific crisis or country, and a dedicated cost-effectiveness assessment should be conducted at the time.

Access to medicines and hepatitis C in Africa: can tiered pricing and voluntary licencing assure universal access, health equity and fairness?

BACKGROUND: The recent introduction of Direct Acting Antivirals (DAAs) for treating Hepatitis C Virus (HCV) can significantly assist in the world reaching the international target of elimination by 2030. Yet, the challenge facing many individuals and countries today lies with their ability to access these treatments due to their relatively high prices. Gilead Sciences applies differential pricing and licensing strategies arguing that this provides fairer and more equitable access to these life-saving medicines. This paper analyses the implications of Gilead's tiered pricing and voluntary licencing strategy for access to the DAAs. METHODS: We examined seven countries in Africa (Egypt, Ethiopia, Nigeria, Democratic Republic of Congo, Cameroon, Rwanda and South Africa) to assess their financial capacity to provide DAAs for the treatment of HCV under present voluntary licensing and tiered-pricing arrangements. These countries have been selected to explore the experience of countries with a range of different burdens of HCV and shared eligibility for supply by licensed generic producers or from discounted Gilead prices. RESULTS: The cost of 12-weeks of generic DAA varies from $684 per patient treated in Egypt to $750 per patient treated in other countries. These countries can also procure the same DAA for 12-weeks of treatment from the originator, Gilead, at a cost of $1200 per patient. The current prices of DAAs (both from generic and originator manufacturers) are much more than the median annual income per capita and the annual health budget of most of these countries. If governments alone were to bear the costs of universal treatment coverage, then the required additional health expenditure from present rates would range from a 4% increase in South Africa to a staggering 403% in Cameroon. CONCLUSION: The current arrangements for increasing access to DAAs, towards elimination of HCV, are facing challenges that would require increases in expenditure that are either too burdensome to governments or potentially so to individuals and families. Countries need to implement the flexibilities in the Doha Declaration on Trade Related Intellectual Property Rights agreement, including compulsory licensing and patent opposition. This also requires political commitment, financial will, global solidarity and civil society activism.