Shit Happens with the A Team

September, 16, 2022 | 14 Comments

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  1. Shit Happens with the A Team

    A perfunctory look at Messrs. James Gordon McMurray MD and Robert Reisenberg MD and conclusions of Investigators to one failing of life and one death – wherever you look for them, up pops Shit Happens with the A Team | Dr. David Healy

    In the opinion of the investigator, there was no reasonable possibility that the cerebrovascular accident was related to the study intervention, concomitant medications, or clinical trial procedures, but rather it was related to hypertension and congestive heart failure. Pfizer concurred with the investigator’s causality assessment.

    In the opinion of the investigator, there was no reasonable possibility that the arteriosclerosis was related to the study intervention, concomitant medications, or clinical trial procedures, but rather it was related to suspected underlying disease. Pfizer concurred with the investigator’s causality assessment.

    The Pfizer nominees, one in waterworks and one in psychiatry –

    Shit happens –

    ‘whatever is wrong with you we have the answer.’

    Riding High on the Back of – Paroxetine/Seroxat…

    Andrew Witty, UnitedHealth Group CEO, joins ‘Squawk on the Street’ to discuss the company’s ability to lower health costs, how Covid trends fed into the company’s earnings beat and why the company is continuing to do deals.

    https://www.cnbc.com/video/2022/07/15/our-external-growth-was-at-the-same-rate-as-internal-growth-rate-says-unitedhealth-group-ceo.html

    Squark on the Street –

    The A Team –

    https://www.youtube.com/watch?v=h0L78S_Ln9o&t=1s

    ‘Embrace the Opportunity’ …

  2. Dear Professor Healy – You say that sales of Brexitalone have been disappointing – I think they are rather satisfying.

    It looks like Sage and Biogen will now promote Zuranolone in capsules for post partum depression.

    https://investors.biogen.com/news-releases/news-release-details/sage-therapeutics-and-biogen-announce-phase-3-skylark-study

    It seems to me that placebo is pretty effective as well.

    n.b. although this was a study into Severe Postpartum Depression, any patients “at significant risk of suicide” were excluded from the trial.

    https://clinicaltrials.gov/ct2/show/NCT04442503

  3. This is one of the companies contracted to give the autumn booster in UK Starting with the most vulnerable – the public is unaware of their criminal record but obviously the government,regulators , scientific advisers, etc could hardly not know

    Violation Tracker Current Parent Company Summary
    Current Parent Company Name: Pfizer
    Ownership Structure: publicly traded (ticker symbol PFE)
    Headquartered in: New York
    Major Industry: pharmaceuticals
    Specific Industry: pharmaceuticals
    Penalty total since 2000: $10,268,423,998
    Number of records: 89
    TOP 5 OFFENSE GROUPS (GROUPS DEFINED) PENALTY TOTAL NUMBER OF RECORDS
    safety-related offenses $5,637,024,615 16
    healthcare-related offenses $3,373,675,000 10
    government-contracting-related offenses $1,148,191,225 20
    competition-related offenses $98,166,568 8
    environment-related offenses $5,629,098 26
    TOP 5 PRIMARY OFFENSE TYPES PENALTY TOTAL NUMBER OF RECORDS
    drug or medical equipment safety violation $5,636,840,000 9
    off-label or unapproved promotion of medical products $3,373,675,000 10
    False Claims Act and related $1,148,191,225 20
    Foreign Corrupt Practices Act $60,216,568 3
    kickbacks and bribery $34,700,000 3

  4. ‘Lingering questions ‘ for Robin and Skylark If a woman isn’t feeling suicidal already there’s a new drug being marketed which could trigger it. And it wouldn’t be the drug to blame it would be the woman’s state of mind obviously – Read all about it mentally ill woman kills herself and newborn child.

    ‘The launch of brexanolone (Zulresso) has been complicated. Not only does brexanolone have to be administered as a 60-hour intravenous infusion, the FDA has raised concerns about two serious adverse events: suicidal ideation after the infusion in one subject and syncope/altered consciousness in another patient. Because of these concerns, Zulresso was approved with a Risk Evaluation and Mitigation Strategy (REMS) and “will only be available to patients through a restricted distribution program at certified health care facilities where the health care provider can carefully monitor the patient.”

    Could be the 9% of women described as ‘non compliant’ had realised the drugs were dodgy and came off them but their their reasons for refusing them aren’t given

    Don’t Forget About Brexanolone’s Little Sister: Zuranolone
    By MGH Center for Women’s Mental Health|January 7th, 2020|Postpartum Psychiatric Disorders|0 Comments

    While we have been talking about using brexanolone, marketed by Sage Therapeutics as Zulresso, for the treatment of postpartum depression, an oral version of this novel antidepressant – SAGE 217 or zuranolone – has been finishing up its Phase 3 trials.

    Like brexanolone, SAGE-217 is a neurosteroid, an analogue of allopregnanolone which is a positive allosteric modulator of the GABA-A receptor. What distinguishes SAGE-217 from brexanolone is that it has much better oral bioavailability and thus does not have to be administered intravenously. It can be taken as an oral medication, just like conventional antidepressants.

    Shortly before the end of the year, Sage Therapeutics released disappointing results for their Phase 3 MOUNTAIN study, where SAGE-217 was being used to treat adults with major depressive disorder (MDD). While this trial showed small but statistically significant differences between SAGE-217 and placebo HAM-D total score on Days 3, 8 and 12, the difference on day 15 was not statistically significant.

    But wait! Post-hoc analysis revealed that in the MOUNTAIN Study, about 9% of the patients in the SAGE-217 group did not have measurable drug levels, suggesting non-compliance in a substantial number of patients taking SAGE-217. When they repeated the analysis, excluding these patients who were non-compliant, they observed a statistically significant difference at all timepoints including Day 15.

    In another analysis, where they included only patients with more severe depressive symptoms (HAM-D > 24, n=124 for SAGE-217 30 mg), a post-hoc analysis demonstrated statistical significance at all timepoints through, and including Day 15.

    Hopefully future studies will help to answer some of these lingering questions.

    SAGE-217 Looks Different in Postpartum Depression Trials

    The results of the Phase 3 trials in women with postpartum depression have clearly received less attention, but in September last year, results of the ROBIN study were presented at the 32nd European College of Neuropsychopharmacology (ECNP) Congress.

    The Phase 3 ROBIN Study evaluated SAGE-217 in 151 women who were diagnosed with severe PPD (HAMD of 26 or higher). Similar to the MOUNTAIN protocol, women were randomly assigned to receive either placebo or SAGE-217 30 mg one daily for 15 days.

    By day 3, women receivingSAGE-217 experienced a greater reduction in HAM-D scores than women receiving placebo (mean reduction, 12.5 vs 9.8; P = .025). The difference in mean HAM-D scores steadily increased up to day 15. At day 15, the mean reduction in HAM-D scores was 17.8 in women receiving SAGE-217 vs. 13.6 in the placebo group (P = .003).

    At day 45, women treated with SAGE-217 continued to show a greater reduction in HAM-D scores than women receiving placebo (19.2 vs 15.1, P = .003). SAGE-217 treatment was also associated with a significant reduction in Hamilton Anxiety Rating Scale compared with placebo, 16.6 vs 12.7 (P = .006).

    SAGE-217 was well-tolerated. Among women receiving SAGE-217, 58% reported adverse events, compared to 51% of the women in the placebo group. No serious adverse events were reported. The most common adverse events in the SAGE-217 group included somnolence (12.8%), headache (9.0%), dizziness (7.7%), upper respiratory tract infection (7.7%), diarrhea (6.4%), sedation (5.1%), and nausea (3.8%).

    There was no indication of an increase in suicidal ideation or suicidal behavior over baseline, as measured with the Columbia Suicide Severity Rating Scale (C-SSRS).

    Looking Forward

    While data from the MOUNTAIN looks a little iffy, the data from the ROBIN study is actually pretty exciting and suggests that SAGE-217 has antidepressant effects in women with severe PPD. Also important is the finding that there were no concerning side effects. The launch of brexanolone (Zulresso) has been complicated. Not only does brexanolone have to be administered as a 60-hour intravenous infusion, the FDA has raised concerns about two serious adverse events: suicidal ideation after the infusion in one subject and syncope/altered consciousness in another patient. Because of these concerns, Zulresso was approved with a Risk Evaluation and Mitigation Strategy (REMS) and “will only be available to patients through a restricted distribution program at certified health care facilities where the health care provider can carefully monitor the patient.” No such worries for SAGE-217.

    We look forward to hearing what the next steps will be.

    Ruta Nonacs, MD PhD

    32nd European College of Neuropsychopharmacology (ECNP) Congress: Presented September 8, 2019.

    Oral drug for postpartum depression aces phase 3 trial (MD Edge)

  5. “at significant risk of suicide” were excluded from the trial.

    They can’t state who is at significant risk – even if you do a good Cytochrome P450 test people can still get akathisia.

    “Most readers likely will figure they are a long way from James Holmes position or that of Irish people locked up in English jails . But if a treatment injures you or a member of your family , you will end up in a similar position. If you attempt to find out what went wrong, you will find yourself up against a system that will almost certainly end up acquitting itself but perhsps even congratulate itself on having kept to procedures every step of which conform to standards of care.”

    Holmes was on a benzodiazepine and Sertraline which was pushed right up which made him worse. Eventually he went cold turkey on 150mg Sertraline and went toxic crazy with akathisia.

    https://en.wikipedia.org/wiki/James_Holmes_(mass_murderer)

    None of these GABA drugs will work the body has to adapt and harms happen.

  6. 1 of 1
    The Better Way Conferences is about to Get Started

    Josh Guetzkow from Jackanapes Junction
    7:52 AM (3 hours ago)

    The Better Way Conferences is about to Get Started

    Josh Guetzkow
    Sep 17

    ▷ LISTEN

    The Better Way Conference is about to get started here in Vienna. There’s a great line-up of speakers. Here’s a link to the livestream.

    I’m in the last panel that starts at 4:30pm Central European Time, 10:30am EST. I’m going to be talking about some of my analyses of the Pfizer clinical trial data that I have not yet written or talked about. See you there!

  7. Sage, Biogen’s zuranolone looks approvable, but will it sell?

    https://pharmaphorum.com/news/sage-biogens-zuranolone-looks-approvable-but-will-it-sell/

    Zuranolone’s rapidity of onset, much faster than conventional monoamine-based antidepressants which can take weeks to kick in, has been behind blockbuster sales projections in MDD. The premise is that the drug can be used to protect people with MDD who may be at risk of self-harm or even suicide quickly.

    Both CORAL and WATERFALL back up the drug’s potential to bring a deeply depressed person back from the brink, and CORAL involved patients with higher levels of anxiety, which may make them more vulnerable.

    Now the big question is whether the drug’s short window of efficacy will make it a commercially-viable product in the marketplace if approved – and meet blockbuster sales projections – and on this point opinion seems to be divided.

    Develop and Refine with Pfizer and GSK –

    Through 3 locations conveniently spaced in the North Alabama area, the New Horizon Research Group is involved with many pharmaceutical companies’ clinical trials to help develop and refine new medical treatments, vaccinations, and diagnostic services. Current and past partnerships include Pfizer, Phathom Pharmaceuticals, GSK, Discovery Life Sciences, Amgen, and the NIH.

    https://newhorizonresearchgroup.com/partnership-with-many-pharmaceutical-companies/

    Robert Riesenberg, MD

    ACMR Founder and Principal Investigator
    Dr. Riesenberg is a research psychiatrist with four decades of experience. His primary focus is on CNS, PK, Healthy Normal, and Child/Adolescent disorders.

    Dr. Riesenberg has been the Principal Investigator in over 600 studies.

    Dr. Riesenberg earned a bachelor’s degree in both Zoology and Psychology from Memphis State University in 1972. In 1975, he earned his MD from the University of Tennessee. He is licensed to practice in Georgia.

    https://cenexelresearch.com/acmr/about/

    Sertraline in children and adolescents with obsessive-compulsive disorder: A multicenter randomized controlled trial

    https://researchexperts.utmb.edu/en/publications/sertraline-in-children-and-adolescents-with-obsessive-compulsive-

    John S. March, Joseph Biederman, Robert Wolkow, Allan Safferman, Jack Mardekian, Edwin H. Cook, Neal R. Cutler, Roberto Dominguez, James Ferguson, Betty Muller, Robert Riesenberg, Murray Rosenthal, Floyd R. Sallee, Karen D. Wagner

    Sertraline appears to be a safe and effective short-term treatment for children and adolescents with obsessive-compulsive disorder.

    Young Minds
    https://www.youngminds.org.uk/young-person/medications/sertraline/

    Open letter to David Haslam, NICE

    https://davidhealy.org/dh-2-dh/

    I am not saying these drugs should never be used. There is evidence they may produce a benefit in paediatric OCD. I can envisage using them in conditions other than OCD. But these drugs cannot be used safely unless clinicians are aware of the true state of the evidence as regards both benefits and hazards, which include making young people suicidal, wiping out their ability to function sexually, perhaps forever, or hooking them to treatments forever.

    Developed and Refined…

  8. So this morning I made the mistake in looking at the trustees of Hospital Rooms.

    https://hospital-rooms.com/trustees

    I knew psychiatrists would be there couldn’t help myself just looked up one – curiosity got me:

    https://www.cambridge.org/core/journals/the-psychiatrist/article/faisil-sethi/3CBBEAD4C6B78FCB28B9C6B234C86309

    “What has been your most controversial idea?

    One of the most challenging scenarios in PICU is the management of the later stages of persistent challenging behaviour. Such patients are often in seclusion, have had many rapid tranquillisation episodes, and may well have unmanaged physical health concerns.

    In a very small number of complex cases, I have worked alongside liaison psychiatry colleagues and medical physicians (from the medical assessment unit) to achieve short-term tranquillisation and allow for urgent medical investigations to be conducted under unconscious sedation. These cases point to the benefits of involving physicians early in the management of severe acute disturbance, and are making me reconsider pharmacological interventions which may be usefully considered in the later stages of rapid tranquillisation clinical protocols.”

    “Later stages of persistent challenging behaviour.”

    This is AKATHISIA – they will totally deny this – which will go from emotional liability to toxic psychosis (Later stages) and it is caused by the drugs the psychiatrists and psych nurses forced and coerced to the patients. The akathisia is turbo charged by this: “have had many rapid tranquillisation episodes”

    “to achieve short-term tranquillisation and allow for urgent medical investigations to be conducted under unconscious sedation.”

    So they are making short-term tranquillisation to make urgent medical investigations when the tranquillisations – going back god knows how long but it’s going to be sometime – in the first place is why the patient is such a horrific state.

    This is torture not care.

    If Dr Faisil Sethi disagrees then I suggest he subject himself to the drugs antipsychotics and benzodiazepines

    “at least 50% of people on low doses of an antipsychotic
    up to 80% or more people on higher doses of an antipsychotic”

    https://rxisk.org/akathisia/

    which have caused the above states and induce akathisia in himself to find out.

    “How do you teach trainees?”

    “I like to use the ward round as a forum for teaching. I am pretty notorious for asking searching clinical questions of my trainees in the ward round. I imagine my trainees will say that I am interested in the physical/mental health interface and the medical aspects of psychiatry.”

    Oh I’d just love it. Those searching questions would come right back at you before you teach them to do what you have been doing.

    They also have an high level employee of Larry Gagosian – just about the most important fine art dealer in the world.

    It’s interesting how psychiatrists have funded fine art – Sackler and how the major art world establishments took the money and didn’t seem to care how they got that money. They like to remind readers of this:

    “The Sacklers have not been charged with a crime.”

    https://www.artnews.com/art-news/news/laura-poitras-nan-goldin-documentary-golden-lion-venice-film-festival-1234639137/

  9. VIDEO – MOUSE DATA…

    A study published Sept. 16 in the New England Journal of Medicine (NEJM) makes a strong case for an Omicron-based COVID-19 booster shot.

    https://www.msn.com/en-gb/health/medical/here-s-why-experts-believe-the-new-omicron-booster-will-work/ar-AA11UP5v?ocid=msedgdhp&pc=U531&cvid=e08b7a4bf25a469aa738a7429e3cfecd

    As more people roll up their sleeves to get the new Omicron booster, data on how well the vaccine protects people not just from serious illness, but also from infection, will become clear. Researchers will also be looking at how long that protection lasts.

    The hope is that better matching the vaccine booster to the circulating strain will afford people more durable protection and lead to yearly, rather than more frequent, shots.

    Edward Dowd
    @EdwardDowd
    ·
    2h
    Bottom line the data is in: The historically much healthier employed US working population experienced higher mortality rates & disability rates in 2021 & 2022 than the overall less healthy US population.

    What changed?

    An experimental mRNA gene therapy inoculation was force mandated onto the working employed population…that’s what!

    My book talks about this evidence in addition to other eye popping UK ONS data & EU Eurostat data.

    https://www.amazon.com/Cause-Epidemic-Sudden-Childrens-Defense/dp/1510776397/ref=mp_s_a_1_1?crid=2ZY48EBT9KFXC&keywords=cause+unknown%2C+ed+dowd&qid=1662157201&sprefix=%2Caps%2C97&sr=8-1

    It’s a shit show folks.

    NEJM
    @NEJM

    A bivalent vaccine with sequences from Wuhan-Hu-1 and omicron BA.1, given as a booster to previously vaccinated persons, was immunogenic in 100% of recipients, with higher levels of neutralizing antibodies against BA.4/BA.5 than a Wuhan-Hu-1 booster.
    https://nej.md/3U6pGvb

    https://www.nejm.org/doi/full/10.1056/NEJMoa2208343

    CONCLUSIONS

    The bivalent omicron-containing vaccine mRNA-1273.214 elicited neutralizing antibody responses against omicron that were superior to those with mRNA-1273, without evident safety concerns. (Funded by Moderna; ClinicalTrials.gov number, NCT04927065.)

     However, the study was not designed to evaluate vaccine effectiveness, and the follow-up time of infection after the booster is limited, which precludes conclusions about protection.

  10. The most common cause of diarrhea is a virus. As yet there is no cure to prevent the shit pouring out of Pfizer even though there is a published account of their criminal activities dating back to 2010 on Violation Tracker.

    STAT | The Readout

    11:18 AM (24 minutes ago)

    Pfizer’s next-gen vaccine comes through
    Before Covid hit, Pfizer’s biggest selling vaccine — really, its biggest product, full stop — was the pneumococcal vaccine Prevnar. Now, there’s a good old-fashioned marketing battle brewing with Merck over the two companies’ next-generation pneumococcal vaccines, which target a bacteria that can cause ear infections, pneumonia, bloodstream infections, and meningitis.

    Yesterday Pfizer said its 20-valent pneumococcal vaccine (that means it targets 20 different strains of the bacterium, compared to Prevnar’s 13) met its goals in a study in European infants. The results were better than those seen in a U.S. study of the same vaccine.

    “We believe the post-dose 3 results in the EU trial are encouraging for EU and U.S. approval odds and help address concerns over the mixed post-dose 3 results reported for the U.S. study,” SVB analyst David Risinger wrote in a note to clients.

    Moderna gives WHO’s mRNA hub some help; Pfizer snubs request,

    Moderna v. Pfizer: What the patent infringement suit means for biotech, Harvard Business Review
    STAT | The Readout
    11:18 AM (13 minutes ago)

    The Readout

    Pfizer’s next-gen vaccine comes through
    Before Covid hit, Pfizer’s biggest selling vaccine — really, its biggest product, full stop — was the pneumococcal vaccine Prevnar. Now, there’s a good old-fashioned marketing battle brewing with Merck over the two companies’ next-generation pneumococcal vaccines, which target a bacteria that can cause ear infections, pneumonia, bloodstream infections, and meningitis.

    Yesterday Pfizer said its 20-valent pneumococcal vaccine (that means it targets 20 different strains of the bacterium, compared to Prevnar’s 13) met its goals in a study in European infants. The results were better than those seen in a U.S. study of the same vaccine.

    “We believe the post-dose 3 results in the EU trial are encouraging for EU and U.S. approval odds and help address concerns over the mixed post-dose 3 results reported for the U.S. study,” SVB analyst David Risinger wrote in a note to clients

    Moderna v. Pfizer: What the patent infringement suit means for biotech, Harvard Business Review

  11. seems to be no cure , it’s very infectious throughout the medical world shit happens
    PHARMALOT
    Analysis of JAMA and NEJM articles finds most authors failed to disclose conflicts

    By Ed Silverman Jan. 19, 2022

    Amid ongoing concerns over conflicts of interest that may affect medical practice, a new analysis finds that 81% of authors whose work appeared in the New England Journal of Medicine and Journal of the American Medical Association — two of the most influential medical journals — failed to disclose payments as required. If there’s nothing to hide why not disclose..the payments may be gross but not illegal

  12. ThunderBirds…

    Read the Posts –

    https://davidhealy.org/gsks-transparency-and-access-journey/

    Here’s that Branded tone again – mentioned in SHIT Happens. A plaintiff note about how the world just doesn’t understand we are the good guys. GlaxoSmithKline (GSK) seem to have bought their own propaganda about being champions of transparency.

    As they mention, the House of Commons has rolled over and put its paws in the air so pleased are they – despite being told by GSK that the UK is not a fit place for Pharma to run trials in. No reference here to the recent fines in the USA for $3 Billion against GSK or the fraud action by New York State against GSK in 2004 hinted at above as the kickstart to GSK’s journey to transparency and access.

    Worryingly, there almost appears to be a hook-up between AllTrials and GSK. AllTrials have been campaigning to have all trials registered. When GSK endorsed this campaign, Ben Goldacre described it as a “cartwheel moment”.

    Any good investigative journalist could likely identify each of the children who became suicidal on paroxetine from the CSRs available on GSK’s website. Pretty well the only additional details that the patient level data that the company refuses to release contains are the patients’ initials. These could easily be redacted. This raises the question as to why GSK are so resistant to making the original case report forms (CRFs) available?

    SHIT Happens – 2

    https://davidhealy.org/shit-happens-2/

    https://davidhealy.org/shit-happens/

    [There’s the Branding again].

    SHIT Happens

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