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.

Five years of non-prescription oseltamivir: effects on resistance, immunization and stockpiling.

OBJECTIVES: In 2007 New Zealand (NZ) became the first country to make oseltamivir (Tamiflu®) available off-prescription. This study investigated the extent of pharmacist supply of oseltamivir over 5 years, including during the influenza A(H1N1) pandemic, and the impact of pharmacist supply of oseltamivir on influenza virus oseltamivir susceptibility, personal stockpiling and influenza vaccine uptake. METHODS: Randomly selected community pharmacies in NZ reported oseltamivir provision by prescription and through pharmacist supply from 1 January 2007 to 15 September 2011. Oseltamivir resistance data on influenza viruses isolated during influenza surveillance from 2008 to 2011 were obtained, along with influenza vaccine uptake data from 2005 to 2011 and influenza detection data. RESULTS: Seventy of 85 eligible pharmacies completed the study (82% response rate). Most supplies of oseltamivir throughout the 5 years were dispensed against a prescription rather than pharmacist supplied, with pharmacist supply responsible for 11% of supplies during the pandemic years (2009-10) versus 27% and 31% during 2007 and 2008, respectively. Pharmacist-supplied oseltamivir did not appear to be associated with the development of resistance, with identified likely stockpiling or with a decline in influenza immunization. Pharmacist supplies largely matched the timing of influenza in the community and peaked in June 2009, as did prescription supplies. CONCLUSIONS: Five years of non-prescription oseltamivir in NZ has resulted in no significant change in the development of resistance or rates of influenza immunization. Supplies remained modest and significant consumer stockpiling through pharmacist supply has not occurred, even during the influenza A(H1N1)pdm09 pandemic in 2009 and 2010. Pharmacists could be better utilized in ensuring fast distribution of antivirals to influenza sufferers during a pandemic.

Oseltamivir storage, distribution and dispensing following the 2009 H1N1 influenza outbreak in Mexico.

PROBLEM: During an influenza outbreak or pandemic, timely access to antivirals is essential to reduce disease severity and transmission. Best practices in antiviral procurement, storage, distribution, prescription and dispensing must be followed for prompt drug delivery. APPROACH: Mexico implemented a national pandemic preparedness plan in 2006 and created a strategic antiviral stockpile. Oseltamivir powder was stored centrally in bulk for distribution to all 31 states and the capital district during an influenza outbreak. LOCAL SETTING: San Luis Potosí, in northern Mexico, was one of the states most intensely affected by the 2009 H1N1 influenza outbreak. RELEVANT CHANGES: The oseltamivir powder was meant to be reconstituted locally but had to be reconstituted centrally during the 2009 influenza outbreak. Doubts arose surrounding the shelf-life of the reconstituted product. As a result of these problems, the first supply of the drug reached San Luis Potosí 11 days after the influenza outbreak had begun. Furthermore, dispensing criteria at the state level had to be changed in conformity with the availability of oseltamivir. LESSONS LEARNT: Antiviral demand forecasts should be based on clearly defined distribution and dispensing criteria and decentralization of some of the medication stockpile should be considered. Mexico's national pandemic preparedness plan needs to be updated in accordance with the lessons learnt in 2009 to improve strategic stockpile management and ensure rapid delivery of oseltamivir to the population.

Is non-prescription oseltamivir availability under strict criteria workable? A qualitative study in New Zealand.

OBJECTIVES: in 2007, New Zealand became the first country to make oseltamivir (Tamiflu) available off prescription. Strict rules for supply were developed to ensure that potential public health benefits were balanced against possible risks. We wished to explore the success of implementing this unique decision through elucidating pharmacists' attitudes to and experiences of non-prescription supply of oseltamivir. METHODS: semi-structured interviews with a maximum variation sample of 26 community pharmacists were conducted and analysed using a framework approach. RESULTS: most participants were positive about non-prescription availability of oseltamivir with the majority appearing to apply the rules successfully. However, some rules were difficult to recall and/or frustrating. Supply did not appear to be driven by potential for commercial gain and the inappropriate requests were manageable. Some of these were driven by other health professionals. Pharmacists valued the manufacturer-supplied 'Pharmacist Protocol' and 'Consultation Record' and kept them ready for use. Certain rules potentially restricted consumer access and pharmacists were generally conservative about recommending the medicine. CONCLUSIONS: while pharmacists welcomed non-prescription oseltamivir, the rules for supply frustrated pharmacists and limited potential public health benefits. If medicines are reclassified with various rules of supply, multiple reminders of the rules for supply to pharmacists and other health professionals are desirable along with the rationale for such rules. Protocols and/or consultation pads for use at time of supply are likely to be valued and are an important aid where there is a risk of faulty recall of rules. Research in the first year of availability may highlight issues to address.

[Scientific research in times of pandemics.] / La ricerca scientifica in tempi di pandemia.

When a pandemic occurs, scientific research moves fast in order to achieve readily results, such as effective therapies to fight the SARS-CoV-2 and vaccines. But this high-speed science, engaged by the emergency and characterized by the explosion of online publications in preprint form not subject to scrutiny by peer reviewers, carries some risks. And it represents a challenge to maintain research integrity and to comply with those globally recognized standard principles of fairness. Competition and the pressure to publish immediately - a way of encouraging rapid data sharing - can favor the dissemination of incomplete if not erroneous results obtained from partial studies, which feed false news, such as the benefits of a drug, and illusory hopes. It is commonly through press releases that "speed science" disseminates information to an audience that wants to be informed and reassured. Financial and political interests often mix with the urgency to find solutions. Covid-19 has highlighted in particular the risk of a politicization of science at the expense of transparency.

Issues in pharmacotherapy of 2009 H1N1 influenza infection.

The pandemic caused by the 2009 H1N1 influenza A virus has been a cause of great concern for healthcare professionals and the scientific community worldwide. Due to the widespread resistance of the virus to adamantanes, pharmacotherapy is currently limited to neuraminidase inhibitors, oseltamivir and zanamivir. The use of neuraminidase inhibitors in India is primarily associated with issues of patient and physician awareness, variability in disease management guidelines, safety and efficacy in the Indian population, need for active drug safety monitoring, and development of resistance due to possible misuse. In addition, other issues like availability of the drugs in retail and stockpiling by the public health authorities need careful introspection. The development of influenza vaccines in India and its adequate availability to the country's populace also poses significant challenges in the management of the pandemic. In light of the limited therapeutic options available for the management of the disease, research on novel targets and pharmacological agents would also be beneficial in addressing the challenges of future outbreaks.

Investment decisions in influenza pandemic contingency planning: cost-effectiveness of stockpiling antiviral drugs.

BACKGROUND: The threat of an influenza pandemic has led to stockpiling of antiviral drugs in order to mitigate a plausible outbreak. If the stockpile would be used in relation to the recent pandemic alert, an investment decision about renewing the stock for a possible subsequent pandemic is essential. The decision should include cost-effectiveness considerations. METHODS: We constructed a cost-effectiveness analysis in the Dutch context, explicitly including risk of an outbreak. Outcomes from a dynamic transmission model, comparing an intervention with a non-intervention scenario, were input in our health economic calculations. RESULTS: Stockpiling was cost-effective from the health-care perspective if the actual risk is 37% for 30 years. If less than 60% of the population would take the antiviral drugs or the attack rate is about 50%, the investment would not be cost-effective from this perspective. CONCLUSION: Risk perception, realistic coverage among population and size of a pandemic are crucial parameters and highly decisive for the investment decision.

Oseltamivir prescribing in pharmacy-benefits database, United States, 2004-2005.

We reviewed information from a US pharmacy benefits manager database from 2004 through 2005 during periods with little influenza activity. We calculated rates of oseltamivir prescriptions to enrollees. Prescription rates increased significantly from 27.3/100,000 in 2004 to 134/100,000 in 2005 (p<0.05), which suggested that personal stockpiling of oseltamivir occurred.

The Tamiflu fiasco and lessons learnt.

Oseltamivir (Tamiflu), a neuraminidase inhibitor, was approved for seasonal flu by US Food and Drug Administration in 1999. A number of randomized controlled trials, systematic reviews, and meta-analysis emphasized a favorable efficacy and safety profile. Majority of them were funded by Roche, which also first marketed and promoted this drug. In 2005 and 2009, the looming fear of pandemic flu led to recommendation by prominent regulatory bodies such as World Health Organization (WHO), Centers for Disease Control and Prevention, European Medicines Agency and others for its use in treatment and prophylaxis of influenza, and it's stockpiling as a measure to tide over the crisis. Serious Adverse Events, especially neuropsychiatric events associated with Tamiflu started getting reported leading to a cascade of questions on clinical utility of this drug. A recent Cochrane review and related articles have questioned the risk-benefit ratio of the drug, besides raising doubts about the regulatory decision of approving it. The recommendations for stockpiling the said drug as given by various international organizations viz WHO have also been put to scrutiny. Although many reviewers have labeled the Tamiflu saga as a "costly mistake," the episode leaves us with some important lessons. This article takes a comprehensive relook on the subject, and we proceed to suggest some ways and means to avoid a similar situation in the future.