The Next Vaccine For Pregnant Women

In case you hadn’t heard, there’s a new vaccine that will likely be marketed toward pregnant women within the next couple of years. It’s for Respiratory Syncytial Virus (RSV) in the newborn – a common cold-like illness that is usually mild in healthy people. Nearly all children will have had an infection by their second birthday – according to the CDC, and of those who have an infection before 6mths of age, around 1-2% will be hospitalised, due to complications such as bronchiolitis or pneumonia [1].

The quest for an RSV vaccine actually began decades ago, and it had disastrous beginnings.

In the early 1960’s, an RSV vaccine, propagated on human embryonic kidney cells, and passaged through monkey cells, before being inactivated with formalin, and adjuvanted with aluminium, was trialled on infants, with disastrous results. Up to 80% of vaccinated infants were hospitalized with severe lower-respiratory infections, and two babies died [2].

It took scientists nearly four decades to figure out why the vaccine had such tragic results – which just goes to show how little is understood about the very system they seek to tamper with. It was due to “Lack of antibody affinity maturation followed poor Toll-like receptor stimulation”, according to the paper, published in Nature journal, in 2009 [3].

The quest for an RSV vaccine resumed with gusto.

At the forefront of the charge for an RSV vaccine, is Novavax, a biotechnology company with several products currently in the clinical testing stages. Following the announcement of positive results of Phase 2 clinical trials in older adults, in 2015, CEO of Novavax, Stanley Erck declared their RSV vaccine could be “the largest selling vaccine in the history of vaccines in terms of revenue”[4].

Unfortunately, the Phase 3 trial in older adults failed to show efficacy, and the company lost more than $1.5 billion in market value within hours of the announcement, as disappointed investors pulled their money [5].

This gives us some idea of the intense pressure faced by companies to deliver the next new ‘blockbuster’ vaccine. For a company like Novavax, with no products on the market yet, (just the potential of new products), investor confidence is crucial to financing the lengthy clinical trial and regulatory approval process.

Novavax then turned their attention to pregnant women, and in February 2019, announced favourable results (actually, not as favourable as they were hoping for, but nevertheless, they found a way to put a positive spin on them) from a Phase 3 clinical trial on pregnant women. The vaccine, called ‘Resvax’, is not only aluminium adjuvanted, it is also genetically-engineered with nano-particles. The press release stated “Our next steps include meeting with U.S. and European regulators to review these data and to discuss the path forward for licensure” [6].

The trials on pregnant women were funded in part, by an $89 million grant from the Bill and Melinda Gates Foundation, with the stated purpose “to advance to WHO Pre-Qualification the development of a respiratory syncytial virus (RSV) vaccine for maternal immunization to reduce the burden of RSV disease in infants less than six months of age in developing countries”[7-8].

Obviously, the burden of RSV disease falls mainly on developing nations, however, it’s likely that a new RSV vaccine will also be targeted at pregnant women in western countries.

One of the main ways to prevent respiratory disease in infants is via breastfeeding. A study published in British Medical Journal found that among 115 babies who had been hospitalized for RSV infection, only 8 were breastfed [9].

Given that breastfeeding rates are vastly lower in developing countries, one wonders why $89 million (and more) wasn’t spent to increase maternal nutrition and breastfeeding rates. As an example, in West/Central Africa, only a mere 20% of infants are exclusively breastfed for the first six months of their life [10].

One of the main groups promoting the need for an RSV vaccine during pregnancy, is the Oxford Vaccine Group, who admit that almost all infant deaths due to RSV are in developing countries [11].

The director of Oxford Vaccine Group is Andrew Pollard, who holds several patents relating to vaccines [12-13], and is Chair of the UK Department of Health’s Joint Committee on Vaccination and Immunisation, and the European Medicine Agency’s scientific advisory group.

Another member of the Oxford Vaccine Group, Matthew Snape, has been Principal Investigator in clinical trials of numerous RSV vaccine candidates. He is also the Director of the National Immunization Schedule Evaluation Consortium (NISEC) [14].

It is also interesting to note that the CDC has held a patent for an RSV vaccine, since 2010 [15]. How will that affect any future decisions regarding RSV vaccinations being promoted to pregnant women?

References:

[1] CDC, Respiratory Syncytial Virus Infection (RSV), https://www.cdc.gov/rsv/high- risk/infants-young-children.html. Accessed March 2019.

[2] Dudas RA, Karron RA. Respiratory syncytial virus vaccines. Clin Microbiol Rev. 1998;11(3):430-9.

[3] Delgado MF, Coviello S, Monsalvo AC, et al. Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. Nat Med. 2008;15(1):34-41. [4] FierceBiotech, Novavax craters after phase III RSV F vaccine failure; seeks path forward, https://www.fiercebiotech.com/biotech/novavax-craters-after-phase-iii-rsv-f-vaccine-failure- seeks- path-forward. Accessed March 2019.

[5] CNBC, Novavax is down 80%. Here’s why its been really hard to develop an RSV vaccine, https://www.cnbc.com/2016/09/16/heres-why-its-been-really-hard-to-develop-a-vaccine-for- rsv.html. Accessed March, 2019.

[6] Novavax, Press Release: Novavax announces topline results from Phase 3 PrepareTM Trial of Resvax TM for prevention of RSV disease in infants via maternal immunization, http://ir.novavax.com/news-releases/news-release- details/novavax-announces-topline-results-phase-3-preparetm-trial. Accessed March 2019.

[7] Novavax, Bill & Melinda Gates Foundation, https://novavax.com/page/19/bill-and- melinda-gates-foundation. Accessed March 2019.

[8] Bill and Melinda Gates Foundation,How We Work, Grant: Novavax, Inc, https://www.gatesfoundation.org/How-We-Work/Quick-Links/Grants- Database/Grants/2015/09/OPP1127647. Accessed March 2019.

[9] Downham MA, Scott R, Sims DG, Webb JK, Gardner PS. Breast- feeding protects against respiratory syncytial virus infections. Br Med J. 1976;2(6030):274-6.

[10] UNICEF Progress for Children, Nutrition Indicators: Exclusive Breastfeeding, https://www.unicef.org/progressforchildren/2006n4/index_breastfeeding.html. Accessed March 2019.

[11] Oxford Vaccine Group: Vaccine Knowledge Project, Respiratory Syncytial Virus, http://vk.ovg.ox.ac.uk/rsv. Accessed April 2019.

[12] Justia Patents, Vaccine, https://patents.justia.com/patent/20130089571, Accessed April 2019.

[13] Justia Patents, Compositions comprising OPA Protein Epitopes, https://patents.justia.com/patent/20100183676. Accessed April 2019.

[14] Oxford Vaccine Group, Matthew Snape, https://www.ovg.ox.ac.uk/team/matthew-snape. Accessed April 2019.

[15] Anti-RSV Immunogens and methods of Immunization, https://patents.google.com/patent/US8846056?oq=vaccine+inassignee:centers+inassignee:f or+inas signee:disease+inassignee:control. Accessed April 2019.

Vaccines & Cancer: Is There a Connection?

“On August 10th, 1998 our only child, Alexander, was diagnosed with the most common pediatric brain cancer, medulloblastoma. He was two years old. Our lives were shattered. The next six months became a race against time to try to understand the disease, find the appropriate treatment, and save Alexander.

After two brain operations Alexander recovered quickly. We wanted to give our son the most effective cancer therapy possible. After weeks of research, many conversations with parents who had children with brain cancer, and conversations with doctors from all over the world, we selected the Burzynski Clinic in Houston, Texas. We arrived there and incredibly we were turned away. Dr. Burzynski said he was not allowed to accept Alexander. I’ll never forget it. We sat in an examining room. Alexander was smiling at the doctor.

“Why can’t you take Alexander?” I asked Burzynski.

“The FDA dictates who I can and can’t accept,” Burzynski said.

Burzynski explained to us that the FDA would only allow him to accept children who had suffered through chemotherapy and/or radiation and still had “measurable tumor” left in their brains. Alexander hadn’t had either of these “world class treatments” but already endured two brain operations (16 hours of surgery in total) and was tumor free for the moment. He had paid a dear price to be tumor free. His optic nerves had been injured so that his big brown eyes were stuck pointing in opposite directions, he lost the ability to cry and laugh and he temporarily lost the ability to walk.

“Please accept my son. He’s only two years old. His whole life is in front of him. I know your treatment works. I’ve spoken to several parents whose children are here. They had malignant brain tumors like Alexander but now they’re alive and well. You have to treat my son,” I begged.

Dr. Burzynski said simply, “I am sorry but I can’t.” Burzynski was saddened but he was powerless. The FDA had made him turn away many children just like Alexander.

Chemotherapy was started soon after and Alexander died in my arms three months later.”

The above is part of written testimony to Congressman Dan Burton and the Government Reform Committee on Vaccines, held in 1999. The parents went on to outline a number of symptoms occurring after vaccines, that eventually led to a diagnosis of brain cancer. They believed his cancer was linked to the numerous rounds of vaccines he’d had as a baby [1].

They are not the only ones who suspect that vaccines played a part in causing cancer.

In 2001, a letter published in the Daily Mail, went as follows “My daughter had the MMR booster at four and her arm immediately swelled up and she started to feel unwell. Within six weeks, she was diagnosed as having leukaemia, and the doctors we spoke to accepted that the MMR jab was probably the trigger for the disease by overloading her immune system — though they believe she may have been already susceptible to the illness” [2].

It’s not just parent’s wondering. Some doctors and scientists, too, have obviously wondered.

In 1965, Dr. Michael Innis, an Australian pathologist and haematologist, wrote to The Lancet, and outlined how rates of leukemia in children at Brisbane Children’s Hospital between 1958 to 1964 showed a statistically significant association with diptheria-tetanus-pertussis vaccination [3].

In 1994, researchers found that MMR vaccination (among other things) increased the odds ratio of childhood acute lymphocytic leukemia [4].

Researchers in 2007 proposed a correlation between childhood leukemia and the introduction of widespread diptheria vaccination – “the significant peak-age (2–5 years) first appeared after 1940 in Great Britain. Since then, childhood leukemia has almost unchangeable incidence. In 1940 the introduction of immunization against diphtheria on a national scale was begun in Great Britain [5]”.

Nevertheless, the long-term studies required to prove whether vaccines increase cancer risk are not necessary for vaccine approval, nor does the CDC feel they are required…[6].

The following chart shows the incidence of childhood cancers in Australia [7].

Note that the most common age for childhood cancer is in the 0-4 years age group. Also note, that this is the same time period where the average child receives more than 40 different vaccines. The second most common age is in the 10-14 years age group, which coincides with the scheduled booster shots and HPV vaccines for secondary school. The least represented age group in cancer statistics, is the 5-9 years, which happens to coincide with a period where the average Australian child receives no vaccines, or, a yearly flu vaccine at the most [8].

It is also interesting to note that the most common type of cancer in children is acute lymphoblastic leukemia, or ALL [9]. This occurs when there is an overproduction of immature white blood cells in the bone marrow, which prevents the production of red blood cells [10]. It seems plausible that chronic activation of the immune system could potentially cause such a state of affairs – an hypothesis that has already been explored in the scientific literature [11-12]

I have already written here about the fact that excessive stimulation of humoral immunity (which includes antibody production – the aim of vaccination) results in suppression of cell-mediated immunity. This same immune system imbalance has already been shown to play a central role in facilitating tumour growth, invasion and metastasis [13].

In a study of oral cancer patients in Nigeria, those with cancer were found to have significantly higher levels of antibodies, than healthy controls [14]. Did the cancer cause the shift towards antibody production, or did the immune imbalance cause the cancer?

Actually, it was demonstrated as early as 1907, that an inappropriate immune response enhances tumour growth [15]. In the 1950’s, the phenomena of antibodies promoting tumour growth was labelled “immunological enhancement” [16].

Research published in the Journal of Infectious Diseases in 1988 found that one-year-old infants vaccinated with measles vaccine experienced a significant decrease in the level of alpha-interferon produced by lymphocytes. This marked reduction was still evident when the study ended a year later [17].

Interferons are a type of cytokine. These molecules communicate between cells to co-ordinate immune responses that help to expel pathogens. Interestingly enough, interferon therapy is now being used as a cancer treatment [18].

Now, obviously none of this proves that vaccines cause cancer, but until the CDC or others are convinced of the urgency of long-term studies in this area, we are left to surmise and hypothesize, and grieving parents are left to forever wonder. Given that the CDC has a large vested interest in vaccines, with dozens of vaccine-related patents [19]…it’s not likely to be anytime soon…

References:

[1] Testimony of Raphaele Moreau-Horwin & Michael Horwin, Government Reform Committee – Vaccines; Finding the Balance Between Public Safety and Personal Choice. US House of Representatives, 12th August 1999.

[2] Letter, Daily Mail, 25th Jan, 2001.

[3] Innis MD, Letter to the Editor: Immunization and Childhood Leukaemia, The Lancet, 13th March 1965, i605.

[4] Buckley JD, Buckley CM, Ruccione K, et al, Epidemiological characteristics of childhood acute lymphocytic leukemia. Analysis by immunophenotype. The Children’s Cancer Group, Leukemia, 1994, 8(5):856-864.

[5] Ivanovski P, Ivanovski I, Childhood acute lymphoblastic leukemia is triggered by the introduction of immunization against diphtheria, Medical Hypothesis, 2007, 68(2): 324-327.

[6] CDC, Parents Guide to Childhood Immunizations, Part 4: Frequently Asked Questions, https://www.cdc.gov/vaccines/parents/tools/parents-guide/parents-guide-part4.html. Accessed March 2019.

[7] Cancer Australia: Children’s Cancer Statistics, https://childrenscancer.canceraustralia.gov.au/about-childrens-cancer/statistics. Accessed September, 2017.

[8] Ibid

[9] St. Jude Children’s Research Hospital, Acute Lymphoblastic Leukemia (ALL), https://www.stjude.org/disease/acute-lymphoblastic-leukemia-all.html. Accessed March 2019.

[10] Poplack DG (1985) Acute lymphoblastic leukemia in childhood. In: Altman AJ (ed) The Paediatric Clinics of North America. Saunders Philadelphia, pp 669–697.

[11] O’Byrne KJ, Dalgleish AG. Chronic immune activation and inflammation as the cause of malignancy, Brit J Cancer, 2001, 85(4):473-83.

[12] Dalgleish AG, O’Byrne KJ. Chronic immune activation and inflammation in the pathogenesis of AIDS and cancer, Adv Cancer Research, 2002, 84:231-76.

[13] O’Byrne KJ, Dalgleish AG, Browning MJ, et al. The relationship between angiogenesis and the immune response in carcinogenesis and the progression of disease, Eur J Cancer, 2000, 36(2):151-69.

[14] Akinmoladun VI, Arinola OG, Elumelu-Kupoluyi T, Eriba LO. Evaluation of humoral immunity in oral cancer patients from a nigerian referral centre, J Maxillofac Oral Surg, 2013, 12(4):410-3.

[15] Flexner S, Jobling JW. Proceedings of the Society for Exp Bio Med. 1907. p. 461.

[16] Kaliss N. Immunological enhancement of tumor homografts in mice: a review. Cancer Res, 1958, 992-1003.

[17] Nakayama T, Maehara N, Sadaki K, Makino S. Long-term regulation of interferon production by lymphocytes from children inoculated with live measles virus vaccine, J Infect Dis, 1988, 158(6): 1386-1390.

[18] Cancer Research UK, Interferon (Intron A), https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/interferon. Accessed March 2019.

[19] Google search of vaccine-related patents held by CDC, https://www.google.com/search?tbo=p&tbm=pts&hl=en&q=vaccine+inassignee:centers+inassignee:for+inassignee:disease+inassignee:control&tbs=,ptss:g&num=100. Accessed March 2019.

How The Science Gets ‘Settled’

If you’ve heard it once, you’ve heard it a thousand times: The science is settled! If you disagree, you are branded ‘anti-science’ or ‘conspiracy theorist’.

You, too, might have the impression that the science on vaccines (or other drugs) is ‘settled’, and that’s not by accident. Here’s how the drug industry achieves that impression…

Clinical Trials

Almost 75% of U.S. clinical trials in medicine are now funded by the pharmaceutical industry [1].

Naturally, the industry has a huge financial stake in the outcome of these clinical trials – a phase III clinical trial may enrol 1000 – 5000 people over many years, and cost hundreds of millions of dollars to complete. Average cost per trial participant is around $36,000 [2]. That’s a lot of incentive to make it worth your while!

Analysis shows that trials funded by the industry are 5x more likely to recommend the experimental drug as treatment of choice, regardless of whether the results justify it, or not [3].

Clinical trials proceed in phases:

Phase I: Usually small numbers of healthy volunteers 20-100, to ascertain safety and dosage.

Phase II: Usually involves up to several hundred people with the disease/condition, or fits the user profile, to ascertain efficacy and side-effects.

Phase III: Involves several hundred to several thousand volunteers with the disease/condition, to monitor efficacy and adverse reactions.

There a number of ways clinical trials can be manipulated to give the results you want – or the appearance of the results you want…

First, you choose the people who are most likely to give the results you want. If you are looking at the safety of a vaccine, you enrol those who are least likely to have adverse reactions, and exclude those with a history of seizures, recent fevers or illness, or any blood clotting disorder [4]. (In the real world, these very people people are often urged to get the vaccine.)

Other methods used to increase the legitimacy of your product include [5]:

i) Seeding trials: Where a drug company induces a doctor to prescribe a certain drug to their patients, in order to gain feedback on the product. These are usually scientifically meaningless, have no clear end-points, but they are large-scale so represent considerable sales for the company. The doctor usually gets paid to enter patients in the trial.

ii) Switching trials: This is a variant of the seeding trial. Doctors are recruited to switch their patients from their usual treatment, to a new treatment. Again, the drug companies know that this will often lead to long-term customers.

iii) post-marketing surveillance: This is yet another variant of the seeding and switching trials, although with more scientific justification, as they are often published, and can provide important data on adverse effects. Again, doctors are paid substantial sums, and the patients may believe they are getting new and ‘better’ treatments.

iv) Dosage: The dose can be manipulated in order to give the desired results. For example, a competitor drug may be given at less-than-optimal dosage, to make the studied drug look more effective. Or the competitor drug may be given at higher-than-optimal dosages, to make the studied drug look safer.

v) Economic evaluations: These can be easy to manipulate, because they are too complex for the average journal editor or reader to fully understand.

Medical Journals

Now, when you get the favourable ‘results’, you have to let the world know all about it! A major randomised trial with favourable results, published in a prestigious journal, is a major win for a drug company, and an essential step in creating a ‘blockbuster’ drug [6-7].

A 2010 review of six major medical journals found that studies funded by industry are cited more often than those funded by other sources – more than twice as often in some journals [8].

So, if the industry-funded studies are more likely to recommend the drug in question (regardless of actual results), and then those same studies are used as a foundation for other research, being cited far more often than independent studies…can you see how the drug industry is able to build up an impression of their products being ‘rigorously tested’ and ‘highly effective’?

 The industry has figured out another way to keep their products in the editorial pages – it’s called ‘ghost-writing’. The drug company pays a writer to create an article containing ‘key marketing messages’, which is then sent to a doctor, who agrees to have his/her name attributed to the work in exchange for payment, before it is submitted to medical publications. Studies suggest that anywhere from 8% to 75% of journal articles may be ghost-written [9].

Clearly, this might appeal to some doctors who want the prestige of being a published author, quite apart from the financial incentive. The pharmaceutical company has final control over the paper, and if a doctor is not compliant enough, they simply get no further projects [10-11].

In many cases, if not all, the ghost-writer and the honorary author have not even viewed the raw data, they have merely been supplied with a summary from the sponsor company [12]. The honorary author is usually chosen because of their credentials, and their ability to influence other prescribers [13].

Of course, the desired effect of all this published data is threefold: a) it gives the appearance that the drug is thoroughly researched and widely accepted, b) which boosts doctor and patient confidence, c) while simultaneously providing an edge over rival products.

But…peer review!

At the heart of the scientific process is the concept known as peer review – where an author’s work is subjected to the scrutiny of other experts in the same field, before being published. The public perception is that the peer review process acts like a stop-gap that upholds the integrity of the scientific process, and filters out errors or fraud, but does it really?

The British Medical Journal decided to test for themselves how reliable the peer-review process is, by inserting major errors into papers before sending to reviewers. Some reviewers didn’t pick up any of the errors, while most picked up only about a quarter. Nobody picked up all the errors [14 -15].

So far, the evidence suggests that the peer review process is ‘slow, expensive, ineffective, something of a lottery, prone to bias and abuse, and hopeless at spotting errors and fraud [16] – but of course, the average internet troll doesn’t know that, yet!

The New England Journal of Medicine has long been ‘the journal to beat’ [17], yet two former editors-in-chief left their role in the top job, and went on to publish books exposing the excessive influence of the drug industry [18-19].

Meta-Analysis

A meta-analysis looks at data from multiple studies, and is used as part of systematic review. Naturally, these are useful and important in the interpretation of data.

A systematic review of vaccine meta-analyses, found that the methodological quality of all 121 meta-analyses included in the review (100%), were unsatisfactory. “The most frequent limitations include non-comprehensive bibliographic research; bias in the selection of the studies; lack of quality assessment of individual studies; absence of evaluation of heterogeneity among studies and publication bias” [20].

So, 100% of the vaccine meta-analysis cherry-picked the studies they wanted to include, in order for the ‘systematic review’ to show the results they wanted…These are the same meta-analyses that are used to guide government policies and legislation, WHO guidelines, doctors opinion…

The Role of Media

In order to further spread the good news of your product, you also need to make some news headlines, via press releases. The media are usually fairly compliant – they want a catchy headline, and…after all, drug companies do help to fund their jobs, via billions of dollars in advertising revenue [21].

A review of health news and current affair items on free-to-air TV in Sydney, Australia, estimated that up to 42% may have ‘been triggered by press releases and other forms of publicity [22].

Advertising and press releases are not the only way the pharmaceutical industry can influence the media. Another avenue is through a situation known as an interlocking directorate. This occurs when the director of one company sits on the board of directors of another company.

Many of the major news corporations have directors who also sit on director boards for pharmaceutical companies – and these cosy relationships have been shown to effect how health news is portrayed [23].

According to research, ‘the media can play an important role in influencing both the demand and supply of medical treatments, regardless of evidence of effectiveness [24].

Media coverage can increase uptake of the seasonal influenza vaccine, especially if reported in a headline, that includes words such as ‘vaccine shortage’ [25]. (Creates a sense of urgency.)

The so-called ‘swine flu pandemic’, which turned out to be more panic than pandemic, featured experts and academics making media appearances, promoting the use of retroviral drugs. It was later found that those who promoted retroviral drugs, were 8 times more likely to have links to industry – via research grants, honorarium payments, advisory roles, employment, board membership, speaker’s fees, etc – than those who did not comment on their use [26].

Getting Your Product Approved

Of course, all your journal articles and press releases are kind of pointless if you can’t get your drug through the regulatory process. In the US, UK, Australia and Canada, the regulatory agencies are all funded by industry (user-pays system), rather than by government [27-30].

Congressional investigations and reports have made damning conclusions on both the CDC and FDA: The Committee’s investigation has determined that conflict of interest rules employed by the FDA and CDC have been weak, enforcement has been lax, and committee members with substantial ties to the pharmaceutical companies have been given waivers to participate in committee meetings” [31].

If that’s not enough, you also have the ‘revolving door’ between government and industry – former employees now hired by drug companies to liaise with their former work-mates in the regulatory system. Studies suggest that more than half of former assessors at the FDA move on to positions within the pharmaceutical industry [32] – obviously their ‘inside knowledge’ is extremely valuable to the drug companies.

Occasionally, the door swings in the opposite direction – pharma employees moving into government jobs. The current secretary of the Department of Health and Human Services (HHS), Alex Azar was formerly a pharmaceutical lobbyist, and president of the US division of pharmaceutical giant Eli Lilly and Co [33]. In case you are not American, like myself, the HHS department guides the nation’s healthcare programs and policies, so…fairly influential.

Regulatory agents are not only funded by industry, as we have already noted, but they also rely on industry to conduct the trials, provide the safety data, and notify them of any issues that may arise post-licensure. The agencies themselves do not conduct clinical trials [34-37].

The Fate of Failed Clinical Trials

Now, what happens if, despite your best efforts, the clinical trials still didn’t give the results you wanted? You can still salvage your reputation by:

a) Just cut the trial short – to save money [38-40], or

b) Simply decide not to publish unfavourable trial results, even though doing so is considered to be scientific malpractice [41-42].

Research shows that less than half of government-funded clinical trial results are published in peer-reviewed medical journals within 30 months of trial completion [43].

One pharmaceutical company managed to suppress trial results for seven years, when they revealed that the drug in question was no more effective than cheaper generic formulations [44].

That, my friends, is a tiny glimpse into how science gets ‘settled’.

Any questions?

References

[1] Bodenheimer, T. 2000. Uneasy alliance: Clinical investigators and the pharmaceutical industry. New England Journal of Medicine 342:1539-1544.

[2] pHRma: Biopharmaceutical industry-sponsored clinical trials: impact on state economies, http://phrma-docs.phrma.org/sites/default/files/pdf/biopharmaceutical-industry-sponsored-clinical-trials-impact-on-state-economies.pdf. Accessed September, 2017.

[3] Als-Nielsen B, Chen W, Gluud C, Kjaergard LL. Association of Funding and Conclusions in Randomized Drug Trials A Reflection of Treatment Effect or Adverse Events?. JAMA. 2003;290(7):921–928.

[4] US National Library of Medicine: ClinicalTrials.gov. Hepatitis A vaccine, Inactivated and Measles, Mumps, Rubella and Varicella Virus Vaccine Live Safety Study, https://www.clinicaltrials.gov/ct2/show/NCT00326183?term=vaccine&recrs=e&cond=varicella&age=0&phase=3&fund=2&rank=4. Accessed October, 2017.

[5] Smith R. Medical journals and pharmaceutical companies: uneasy bedfellows. BMJ : British Medical Journal. 2003;326(7400):1202-1205.

[6] Guyatt GH, Naylor D, Richardson WS, et al. What is the best evidence for making clinical decisions? JAMA. 2000 Dec 27; 284(24):3127-8.

[7] Smith R. Medical journals are an extension of the marketing arm of pharmaceutical companies. PLoS Med. 2005 May; 2(5):e138.

[8] Lundh A, Barbateskovic M, Hrobjartsson A, Gotzche pC. Conflicts of interest at medical journals: The influence of industry-supported randomised trials on journal impact factors and revenue-cohort study, pLOS One, 2010, 7(10): e1000354.

[9] Hill M. Ghosts in the Medical Machine, Philadelphia Inquirer, 20th September 2009.

[10] Petersen M. Madison Ave. Plays Growing Role in Drug Research. New York Times. 2002 November 22. Available at: www.nytimes.com/2002/11/22/business/22DRUG.html?pagewanted=5, Accessed January, 2019.] [Ngai S, Gold J. L, Gill

[11] Rochon P.A. Haunted Manuscripts: Ghost Authorship in the Medical Literature. Accountability in Research. 2005;12:p103–114.

[12] McHenry L. Of Sophists and Spin-Doctors: Industry-Sponsored Ghostwriting and the Crisis of Academic Medicine. Mens Sana Monographs. 2010;8(1):129-145.]

[13] Ibid.

[14] Godlee F, Gale CR, Martyn CN. Effect on the quality of peer review of blinding reviewers and asking them to sign their reports: a randomized controlled trial. JAMA. 1998 Jul 15; 280(3):237-40.

[15] Schroter S, Black N, Evans S, et al.Effects of training on quality of peer review: randomised controlled trial.BMJ. 2004 Mar 20; 328(7441):673.

[16] Smith R. The trouble with medical journals. Journal of the Royal Society of Medicine. 2006;99(3):115-119.

[17] Smith R. Lapses at the New England Journal of Medicine. Journal of the Royal Society of Medicine. 2006;99(8):380-382.

[18] Angell M. The Truth About Drug Companies: How They Deceive Us and What To Do About It. New York: Random House, 2005.

[19] Kassirer JP. On The Take: How Medicine’s Complicity With Big Business Can Endanger Your Health. New York: Oxford University Press, 2004.

[20] De Vito C, Manzoli L, Marzuillo C, et al. A systematic review evaluating the potential for bias and the methodological quality of meta-analyses in vaccinology, Vaccine, 2007, 25(52):8794-806.

[21] CBS News, Drug Ads: $5.2 billion annually – and rising, https://www.cbsnews.com/news/drug-ads-5-2-billion-annually-and-rising/. Accessed September, 2017.

[22] Chapman S, Holding SJ, Ellerm J, et al. The content and structure of Australian television reportage on health and medicine, 2005–2009: Parameters to guide health workers. Med J Aust, 2009, 191(11) 620–624.].

[23] Fairness and Accuracy in Reporting: Single-payer and interlocking directorates, The corporate ties between insurers and media companies, http://fair.org/extra/single-payer-and-interlocking-directorates/. Accessed February, 2017.

[24] Benelli E (2003) The role of media in steering public opinion on healthcare issues. Health Policy 63: 179–186.

[25] Yoo B-K, Holland ML, Bhattacharya J, Phelps CE, Szilagyi PG. Effects of Mass Media Coverage on Timing and Annual Receipt of Influenza Vaccination among Medicare Elderly. Health Services Research. 2010;45(5 Pt 1):1287-1309.

[26] Wise Jacqui. Academics who spoke out on swine flu risks were more likely to have industry links, study finds BMJ, 2013; 347 :f6758.

[27] Frontline. How independent is the FDA? http://www.pbs.org/wgbh/pages/frontline/shows/prescription/hazard/independent.html. Accessed October, 2017.

[28] House of Commons Health Committee. The Influence of the pharmaceutical industry: Fourth Report of Session 2004-2005.Published on 5 April 2005 by authority of the House of Commons London: The Stationery Office Limited.

[29] Government of Canada. Funding and Fees, https://www.canada.ca/en/health-canada/services/drugs-health-products/funding-fees.html. Accessed October, 2017.

[30] Productivity Commission. Submission To The Productivity Commission, re: Federal Government Cost Recovery, https://www.pc.gov.au/inquiries/completed/cost-recovery/submissions/medical_industry_association_of_australia_/sub012.pdf. Accessed October, 2017.

[31] FACA: Conflicts of Interest and Vaccine Development: Preserving the Integrity of the Process, Before the Government Reform Committee of the House of Representatives, 106th Congress, June 15, 2000.

[32] Bien, J., & Prasad, V. (2016). Future jobs of FDA’s haematology-oncology reviewers. BMJ (Online), 354, i5055.

[33] Brennan Z. Revolving Door Between Industry and FDA Continues to Spin, Regulatory Affairs Professionals Society, 6th September, 2018.

[34] US Food and Drug Administration. Clinical Trials: What patients need to know, https://www.fda.gov/forpatients/clinicaltrials/. Accessed October, 2017.

[35] Medicines and Healthcare products Regulatory Agency. Medicines and Medical Devices Regulation: What you need to know, http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con2031677.pdf. Accessed October, 2017.

[36] Government of Canada. Clinical trials and drug safety, https://www.canada.ca/en/health-canada/services/healthy-living/your-health/medical-information/clinical-trials-drug-safety.html. Accessed October, 2017.

[37] Therapeutic Goods Administration. TGA regulatory framework, https://www.tga.gov.au/tga-regulatory-framework. Accessed October, 2017.

[38] Psaty BM, Rennie D. Stopping medical research to save money. A broken pact with researchers and patients.  JAMA2003;289:2128-2131.

[39] Canadian Association of University Teachers: The Olivieri Report, https://www.caut.ca/docs/af-reports-indepedent-committees-of-inquiry/the-olivieri-report.pdf?sfvrsn=0. Accessed September, 2017.

[40] Lievre M, Menard J, Bruckert E.  et al.  Premature discontinuation of clinical trial for reasons not related to efficacy, safety, or feasibility.  BMJ.2001;322:603-605.

[41] Bodenheimer, T. 2000. Uneasy alliance: Clinical investigators and the pharmaceutical industry. New England Journal of Medicine 342:1539-1544.

[42] Chalmers I. Underreporting research is scientific misconduct.  JAMA.1990;263:1405-1408.

[43] Ross Joseph S, Tse Tony, Zarin Deborah A, Xu Hui, Zhou Lei, Krumholz Harlan M et al. Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis BMJ 2012; 344 :d7292.

[44] Vogel G. Long-suppressed study finally sees light of day.  Science.1997;276:525-526. p

10 Reasons Why The Flu Shot is Worse Than Useless

  1. The number of “flu deaths” each year, used to scare people into getting vaccinated, is grossly inaccurate. There are several reasons for this, the main one being that so-called “flu deaths” are lumped in with deaths from pneumonia and ‘influenza-like illnesses’, and ‘respiratory and circulatory causes’ [1]. Out of all those deaths, the CDC ‘estimates’ how many were caused by influenza. Given that a) states are not even required to report flu cases or deaths in adults, and b) the ‘CDC feels it is important to convey the full burden of seasonal flu to the public’ (their words, not mine), one can just imagine how inflated their ‘guesstimates’ are!
  2. Seasonal flu vaccine makes you more susceptible to other respiratory infections [2].
  3. Influenza-related deaths have actually increased, as vaccination rates have increased [3].
  4. Numerous reviews have found that there is evidence of widespread manipulation of data in flu vaccine studies, and what’s more, no measurable benefits in vaccinating healthcare workers, young children, healthy adults, pregnant women or the elderly [4-8]. Actually, let’s just say that there are no measurable benefits for anybody [9].
  5. Flu vaccine induces auto-antibodies against gangliosides in the brain [10]. Gangliosides are found throughout the body, especially the central nervous system and play an important role in many cell functions.
  6. Flu vaccine makes people more susceptible to pandemic influenza strains [11].
  7. After three consecutive years, people who receive the annual flu vaccine, are more likely to get influenza [12].
  8. The prestigious Cochrane Review found that 71 people would need to be vaccinated in order to prevent one case of influenza…while at the same time concluding that only 10% of the studies included in their review had good methodological quality. Therefore, even this unimpressive finding is likely to be vastly over-inflated [4].
  9. Vaccines only target A and B strains of influenza, which account for approximately 10% of known circulating strains. Remembering that “efficacy” is based on ability to produce antibodies, which does not equal immunity anyway [4].
  10. Multidose flu vaccines (such as trivalent and quadrivalent vaccines) contain thimerosal, which is 50% ethylmercury by weight. Ethylmercury is highly toxic, converts to inorganic mercury, persists in the brain for many years. Oh, and it also suppresses the immune system… [13].

References:

[1] CDC. Influenza (Flu): Estimating seasonal influenza-associated deaths in the United States, https://www.cdc.gov/flu/about/disease/us_flu-related_deaths.htm. Accessed December, 2018.

[2] Cowling BJ, Fang VJ, Nishiura H, et al. Increased risk of non-influenza respiratory virus infections associated with receipt of inactivated influenza vaccine, Clin Infect Dis, 2012, 54(12):1778-1783.

[3] Simonson L, Reichert TA, Blackwelder WC, Miller MA, Benefits of influenza vaccination on influenza-related mortality among elderly in the US: an unexpected finding, Intern Cong Series, 2004, 1263: 163-167.

[4] Jefferson T, Di Pietrantoni C, Rivetti A, et al. Vaccines for preventing influenza in healthy adults, Cochrane Database Syst Rev, 2010, 7(7): CD001269.

[5] Thomas RE, Jefferson T, Lasserson TJ. Influenza vaccination for healthcare workers who work with the elderly, Cochrane Database Syst Rev, 2010, 17(2): CD005187.

[6] Szilagyi PG, Faibrother G, Griffin MR, et al. Influenza vaccine effectiveness among children 6-59 months of age during 2 influenza seasons: a case-cohort study, Arch Pediatr Adolesc Med, 2008, 162(10): 943-951.

[7] France EK, Smith-Ray R, McClure D, et al. Impact of maternal influenza vaccination during pregnancy on the incidence of acute respiratory illness visits among infants, Arch Pediatr Adolesc Med, 2006, 160(12): 1277-1283.

[8] Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza: a systematic review and meta-analysis, Lancet Infect Dis, 2012, 12(1)36-44.

[9] Simonsen L, Reichert TA, Viboud C, et al. Impact of influenza vaccination on seasonal mortality in the US elderly population, Arch Intern Med, 2005, 165(3): 265-272.

[10] Nachamkin I, Shadomy SV, Moran AP, et al. Anti-ganglioside antibody induction by swine and other influenza vaccines: insights into vaccine-associated Guillain-Barre syndrome, J Infect Dis, 2008, 198(2): 226-233.

[11] Bodewes R, Kreigtz JH, Baas C, et al. Vaccination against human influenza A/H3N2 virus prevents the induction of heterosubtypic immunity against lethal infection with avian influenza A/H5N1 virus, PLoS One, 2009, 4(5): e5538.

[12] Skowronski D, Chambers C, Sabaiduc S, et al. A perfect storm: impact of genomic variation and serial vaccination on low influenza vaccination effectiveness during 2014-2015 season, Clin Infect Dis, 2016, 63(1): 21-32.

[13] Loison E, Poirier-Beaudouin B, Seffer V, et al. Suppression by thimerosal of ex-vivo CD4+ T-cell response to influenza vaccine and induction of apoptosis in primary memory T cells, PLoS One, 2014, 9(4): e92705