Tamiflu lacks evidence of being effective.  Minimal difference is blown up.  Even without the raw data the benefit was shown to be a reduction of 1 day of illness, a benefit approximately equaled the side effects, and certainly not worth taking when the cost is factored in.  Recognizing the inadequacies of journal articles Cochrane sought the raw data so as to improve their studies of Tamiflu.  On bias:  A study published in the NEJM:  “showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall” for 37 studies reviewed (also at http://healthfully.org/index/id9.html).  The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials; these are published in the Cochrane Review. 

Search for evidence goes on

BMJ 2012; 344 doi: 10.1136/bmj.e458 (Published 17 January 2012); Cite this as: BMJ 2012;344:e458

Oseltamivir (Tamiflu) is a multibillion pound success for the Swiss drug manufacturer Roche, with profits rocketing during the pandemic influenza of 2010. In the UK, general practitioners can now prescribe it to anyone with flu and the drug is the mainstay of influenza treatment in critical care. But how has this happened to a drug whose effectiveness is not backed up by publicly available evidence and whose manufacturer has broken successive pledges to make full study reports available? As a new Cochrane Collaboration meta-analysis is published, Deborah Cohen investigates

Researchers working on the latest Cochrane Collaboration meta-analysis of the evidence on oseltamivir (Tamiflu) have claimed that the drug’s manufacturer is still denying them access to full trial data. This is despite Roche, the Swiss company behind oseltamivir, pledging in the BMJ two years ago that it would make “full study reports” available.1 As a consequence, confusion still surrounds the evidence on oseltamivir and guidance on how doctors should prescribe it.

The latest Cochrane review on oseltamivir, a drug on which governments around the world have spent billions of pounds, is published today (18 January). But the Cochrane reviewers have received only part of the clinical study reports—the summary of the study methods and the results. The company says this is enough for the Cochrane group to conduct their review, but Cochrane denies this.

Meanwhile, GlaxoSmithKline—the makers of the less popular antiviral drug zanamivir (Relenza)—have offered individual patient data. When the BMJ asked Roche why it was refusing to make its data available, despite GSK’s promises, it said it refused to answer until it had had the chance to see the full Cochrane review.

Clinicians can be forgiven for being confused about what the evidence on oseltamivir says. Last September, the UK Department of Health announced that in the event …

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Neuraminidase inhibitors for preventing and treating influenza in children Updated

Wang K, Shun-Shin M, Gill P, Perera R, Harnden A

Published Online:   http://summaries.cochrane.org/CD002744/neuraminidase-inhibitors-for-preventing-and-treating-influenza-in-children January 18, 2012

Influenza (true 'flu) is an infection of the airways caused by the Influenza group of viruses. Influenza occurs most commonly during winter months and can result in symptoms such as fever, cough, sore throat, headache, muscle aches and fatigue. These are usually self-limiting but may persist for one to two weeks. The most common complications of influenza are secondary bacterial infections including otitis media (ear infections) and pneumonia. Influenza infection is also highly contagious and is spread from person-to-person by droplets produced when an infected individual coughs or sneezes.

This update reviews the randomised controlled trial evidence of a class of drugs called the neuraminidase inhibitors in treating and preventing influenza in children. Neuraminidase inhibitors work against influenza by preventing viruses from being released from infected cells and subsequently infecting further cells. Oseltamivir (Tamiflu), an oral medication, and zanamivir (Relenza), an inhaled medication, are currently licensed, whilst laninamivir is undergoing Phase III clinical trials. Neuraminidase inhibitors are usually prescribed to patients presenting with flu-like symptoms during epidemic periods to reduce symptoms or prevent spread of the virus. ….

This review found that treatment with neuraminidase inhibitors was only associated with modest clinical benefit in children with proven influenza. Treatment with oseltamivir or zanamivir shortened the duration of illness in healthy children by about one day. One trial demonstrated that the new neuraminidase inhibitor drug laninamivir reduces duration of illness by almost three days in children with oseltamivir-resistant influenza. The effect of neuraminidase inhibitors in preventing transmission of influenza was also modest; 13 children would need to be treated to prevent one additional case. Neuraminidase inhibitors are generally well tolerated but there will be one extra case of vomiting for every 17 children treated with oseltamivir. Other side effects such as diarrhoea and nausea were no more common in children treated with neuraminidase inhibitors compared to placebo. There is currently no high-quality evidence to support targeted treatment of 'at risk' children (with underlying chronic medical conditions) with neuraminidase inhibitors.

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Drug are marketed on the basis of bio-intervention.  When this occurs without convincing evidence of endpoint benefits, assume that there isn’t.  This is the case with Tamiflu, statins, and many drugs.  

From WIkipedia

As of December 15, 2010, the World Health Organization (WHO) reported 314 samples of the prevalent 2009 pandemic H1N1 flu tested worldwide have shown resistance to oseltamivir.^[4]

Efficacy

On December 8, 2009, the Cochrane Collaboration, which reviews medical evidence, in a review published in the British Medical Journal, announced it had reversed its previous findings that the antiviral drug Tamiflu can ward off pneumonia and other serious conditions linked to influenza. They reported an analysis of 20 studies showed Tamiflu offered mild benefits in terms of duration of symptoms for healthy adults if taken within 24 hours of onset of symptoms, but found no clear evidence it prevented lower respiratory tract infections or other complications of influenza.^[15][16] These findings relate only to its use in healthy adults with influenza, not in patients judged to be at high risk of complications (This is pro-drug bullshit, since Cochrane made no such exception in their reversal, they couldn’t since Roche never supplied the promised evidence—jk). Tamiflu may still be a useful drug for reducing the duration of symptoms, although for this use it still has yet to be compared with NSAIDs or paracetamol.^[17]

Mechanism of action  {mechanism of action is a marketing ploy and doesn’t entail effective intervention--jk}

The prodrug oseltamivir is itself not virally effective; however, once in the liver, it is converted by natural chemical processes, hydrolysed hepatically to its active metabolite, the freecarboxylate of oseltamivir (GS4071).^[5]

Oseltamivir is a neuraminidase inhibitor, serving as a competitive inhibitor of the activity of the viral neuraminidase (NA) enzyme upon sialic acid, found on glycoproteins on the surface of normal host cells. By blocking the activity of the enzyme, oseltamivir prevents new viral particles from being released by infected cells.^[5]

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Technical article from Cochrane Library on Tamiflu supporting findings of its ineffectiveness

Tamiflu Cochrane Library

AB: BACKGROUND: The effectiveness and safety of amantadine (AMT) and rimantadine (RMT) for preventing and treating influenza A in adults has been systematically reviewed. However, little is known about these treatments in children and the elderly. OBJECTIVES: To systematically review the effectiveness and safety of AMT and RMT in preventing and treating influenza A in children and the elderly. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2) which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1966 to June week 3, 2011) and EMBASE (1980 to June 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing AMT and/or RMT with placebo, control, other antivirals or different doses or schedules of AMT or RMT, or both, or no intervention, in children and the elderly. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and assessed methodological quality. We resolved disagreements by consensus. In all comparisons except for one, we separately analysed the trials in children and the elderly using Review Manager software. MAIN RESULTS: A total of 12 studies involving 2494 participants (1586 children and adolescents and 908 elderly) compared AMT and RMT with placebo, paracetamol (one trial; 69 children) or zanamivir (two trials; 545 seniors). All studies were RCTs but most were still susceptible to bias. Two trials in the elderly had a high risk of bias because of incomplete outcome data. In one of those trials there was also a lack of outcome assessment blinding. Risk of bias was unclear in 10 studies due to unclear random sequence generation and allocation concealment. Only two trials in children were considered to have a low risk of bias.  AMT was effective in preventing influenza A in children. A total of 773 participants were included in this outcome (risk ratio (RR) 0.11; 95% confidence interval (CI) 0.04 to 0.30). The assumed risk of influenza in the control group was 10 per 100 and the corresponding risk in the RMT group was one per 100 (95% CI 0 to 3). The quality of the evidence was considered low. For treatment purposes, RMT was beneficial for abating fever on day three of treatment. For this purpose one study was selected with low risk of bias and included 69 children (RR 0.36; 95% CI 0.14 to 0.91). The assumed risk was 38 per 100 and the corresponding risk in the RMT group was 14 per 100, 95% CI 5 to 34. The quality of the evidence was moderate.  RMT did not show a prophylactic effect against influenza in the elderly, but the quality of evidence was considered very low. There were 103 participants (RR 0.45; 95% CI 0.14 to 1.41, for an assumed risk of 17 per 100 and a corresponding risk in the RMT group of 7 per 100, 95% CI 2 to 23). We did not identify any AMT trials in the elderly that met our inclusion criteria.  There was no evidence of adverse effects of AMT and RMT in children or an adverse effect of RMT in the elderly. We did not identify any AMT trials in the elderly that met our inclusion criteria. AUTHORS' CONCLUSIONS: AMT is effective in preventing influenza A in children but the NNTB is high (NNTB: 12 (95% CI 9 to 17). RMT probably helps the abatement of fever on day three of treatment, but the quality of the evidence is poor. Due to the small number of available studies, we could not reach a definitive conclusion on the safety of AMT or the effectiveness of RMT in preventing influenza in children and the elderly. AMANTADINE AND RIMANTADINE TO PREVENT AND TREAT INFLUENZA A IN CHILDREN AND THE ELDERLY: Influenza is a respiratory infection in which cough, runny nose, headache and fever are frequent manifestations. Most symptoms resolve without treatment within three to seven days. However, hospitalisation, pneumonia and even death may occur as rare complications of the illness, especially among children and the elderly. Pandemics are also a reason for concern. They occur when influenza spreads globally, infecting 20% to 40% of the world's population, resulting in as many as 10 million deaths.  Oseltamivir (also known as Tamiflu) is currently used for patients with influenza on the recommendation of the World Health Organization (WHO). In previous pandemics, the virus was susceptible to amantadine and rimantadine. So, if they are safe and if the circulating strain proves to be susceptible to these drugs, they could be a less expensive alternative in the management of influenza. This reinforces the importance of conducting reviews on a variety of drugs for the treatment and prevention of influenza. We conducted a review of trials in children and the elderly groups. We selected 12 trials on 1586 children and adolescents and 908 elderly were selected  .Amantadine can prevent influenza in children but it would be necessary to use the drug in up to 17 children during a 14- to 18-week period to prevent one case of influenza. There was no evidence of adverse effects of amantadine in children. We could not reach a conclusion on its use or adverse effects in the elderly, as we did not identify any amantadine trials in the elderly that met our inclusion criteria.  The only observed benefit of rimantadine was in the abatement of fever by day three of treatment in children.  Although it is not the objective of this review, it is possible to speculate if rimantadine can be prescribed in selected cases, such as in children with underlying medical conditions in which fever may lead to complications, or may impair treatment or control of diseases such as diabetes, cardiopulmonary illness and chronic anaemia, such as sickle cell disease. New trials should answer this issue. Due to the small number of studies, we could not reach a definitive conclusion on the safety of amantadine or the effectiveness of rimantadine on preventing influenza in both age groups. Amantadine et rimantadine pour les cas de grippe A chez les enfants et les personnes âgées AMANTADINE ET RIMANTADINE POUR LA PRéVENTION ET LE TRAITEMENT DE LA GRIPPE A CHEZ LES ENFANTS ET LES PERSONNES âGéES: La grippe est une infection respiratoire qui se manifeste généralement par l'apparition de toux, d'écoulements nasaux, de maux de tête et de fièvre. La majorité de ces symptômes disparaissent sans traitement au bout de trois à sept jours. Toutefois, des cas de complications rares de la maladie peuvent entraîner une hospitalisation, une pneumonie, voire la mort, surtout chez les enfants et les personnes âgées. Les pandémies sont également source de préoccupations. Elles apparaissent lorsque la grippe se propage de façon globale, infectant 20 à 40 % de la population et entraînant ainsi la mort de dizaines de millions de personnes.L'oseltamivir (aussi connu sous le nom de Tamiflu) est actuellement préconisé pour les patients atteints de la grippe sur recommandation de l'Organisation mondiale de la Santé (OMS). Lors des pandémies précédentes, le virus était sensible à l'amantadine et la rimantadine. Par conséquent, si leur innocuité est démontrée et que la souche en circulation se révèle être sensible à ces médicaments, ces derniers pourraient représenter une alternative moins coûteuse pour la gestion de la grippe. Ceci renforce l'importance des revues portant sur divers médicaments pour le traitement et la prévention de la grippe. Nous avons réalisé une revue d'essais portant sur des groupes d'enfants et de personnes âgées. Nous avons sélectionné 12 essais totalisant 1 586 enfants et adolescents, et 908 personnes âgées.L'amantadine permet de protéger les enfants de la grippe, mais sa prise doit s'étendre sur une période allant de 14 à 18 semaines chez 17 enfants afin d'éviter son apparition. Aucune preuve n'a permis de démontrer les effets indésirables de l'amantadine chez les enfants. Nous n'avons pu tirer aucune conclusion quant à son administration ou ses effets indésirables chez les personnes âgées car nous n'avons identifié aucun essai réalisé auprès de personnes âgées qui répondaient à nos critères d'inclusion.Les seuls effets bénéfiques observés de la rimantadine étaient une chute de la fièvre le troisième jo<Abstract truncated>

This pattern of manipulation of journal articles is consistent with the marketing science (not medical science) which has taken over the research, published results, and education of care givers, a process that began under the administration of Ronald Regan.   The corporate system puts profits first.  It gave us the Great Depression, the current minor depression, made cigarettes a blockbuster, and it sell bisphosphonates, selective COX inhibitors (VIOXX & Celebrex), Warfarin and Plavix, etc. while their marketing scientists attack the superior off-patent alternatives.  By sorting through their published journal articles and older studies done by independent scientists, I have published hundreds of articles supporting these accusations at www.healthfully.org.  I have struggled with the more recent journal articles, for the peer review process is flawed.  Reviewers do not see the raw data, and scientists are selected on the basis of being PhARMA (the drug industry’s powerful trade organization) friendly.  The articles are consistently slanted.  A group of scientists had obtained through the Freedom of Information Act the raw data submitted to the FDA for approval of neuroleptic drugs.  Comparing the raw data to the published journal articles they found that for the ___ reviewed that they were positive slanted between 11% and 69%, average 32%.  This finding has not been challenged; it was just ignored by the industry, though the study was published in the US’s most prodigious medical journal.  .    , ignored for there is no rebuttal.  Journal articles have positive bias which is not known to the reviewers for they never receive the raw data used to generate the article.  The very process of the researcher submitting the research to the drug company, having the company decide what if anything to publish, and having them often ghost write the journal submission, this is the norm.  There is a chorus of critics, but that doesn’t change the process, because money talks loudest

Inositol hexanicotinate

In 2009, the European Food Safety Authority (EFSA) Scientific Panel on Food Additives and Nutrient Sources Added to Food concluded that nicotinate from IHN is a bioavailable source of niacin.¹⁷ The data available suggests that intestinal absorption of IHN varies widely, with an average of 70% of the administered dose being absorbed into the bloodstream.¹⁸ Although the fraction absorbed is not as high as for NA, the majority of IHN is absorbed and appears to remain intact. Possible direct actions of IHN after absorption have not been demonstrated but are plausible. Metabolism of IHN to release NA can result in the physiological actions of NA, depending on the rate and amount of release. The beneficial lipid-lowering effects of NA and ER-NA are well established, but the beneficial effects of IHN on serum lipids are dependent on the uptake of IHN and the substantial subsequent release of the NA moieties from the IHN molecule.

The available reports indicate that IHN does not produce plasma NA levels sufficient to lower lipids. Humans given oral doses of IHN obtain peak plasma levels of NA at 6–12 h,^19,20 while oral doses of NA result in peak plasma levels of NA at 0.5–1 h.²¹ Interestingly, the peak plasma levels of NA after oral doses of IHN are dramatically lower when compared with those obtained after oral doses of NA; for example, a single oral dose of 1,000 mg NA resulted in a peak plasma level of 30 µg/mL NA,²¹ while 1,000 mg of IHN (weight equivalent to ∼910 mg NA) resulted in a peak plasma level of 0.2 µg/mL NA.²² Similarly, Kruse et al.²³ gave 12 healthy young women 2,400 mg of IHN orally over a 3-hour period and achieved a peak plasma NA level of 0.1 µg/mL. Another experiment conducted in dogs compared the bioavailability of oral doses of 1 g of NA to the same amount of IHN and pentaerythritol tetranicotinate. The peak plasma level of NA was 130 times (approximately 65 µg/mL) greater than the peak plasma level of IHN (approximately 0.5 µg/mL) and 80 times greater than that of pentaerythritol tetranicotinate (0.8 µg/mL).²²

Some reports indicate IHN produces a slight increase in the plasma level of NA but does not have any significant effects on plasma lipid profiles.^22–24 If IHN is, in fact, absorbed intact and hydrolyzed in the body with the release of NA and inositol, the extent of hydrolysis appears to be very low, as evidenced by the low levels of NA found in plasma after IHN ingestion. The significant differences in plasma levels of NA that are achieved after similar oral doses of IHN and NA may account for the different effects observed in clinical studies. In fact, the observed effects of IHN may not be related to its total NA content but rather to a direct effect of IHN itself. Overall, the evidence indicates that IHN produces only slight increases in plasma NA, but these changes are not large enough to significantly alter plasma lipid profiles.²⁵