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.

5 Measles Facts Ignored by Mainstream Media

  1. Nobody knows how many people die globally from measles.

Global death statistics and statistics claiming to prove how many lives are saved by vaccinations are produced via computer modelling through the use of assumptions and mathematical algorithms. Two modelling systems are used: Lives Saved Tool (LiST) is used increasingly by donor organizations, and the WHO/IVB model used by the World Health Organization’s Department of Immunization, Vaccines and Biologicals.

Both have their shortfalls:

For example, WHO modelling assumes that all unvaccinated children will have a measles infection by their 20th birthday [1], and a proportion of those cases (ascertained by expert panel) would die from measles.

The LiST tool assumes that the ‘herd’ is protected when vaccination coverage reaches 90%, even though we know that outbreaks still occur in areas with 99% vaccination rate [2].

As an example of how these different modelling systems, with their inbuilt assumptions, can affect the numbers, researchers estimated measles deaths for the year 2000 via the two modelling systems. One model estimated 671,521 deaths, while the other model estimated 224,084 deaths – less than half [1].

2. Measles is notoriously hard to diagnose.

Once upon a time, anybody with a fever and a generalized rash may have been diagnosed with measles. In 1998, only a mere 14% of measles diagnoses turned out to be correct in Australia [3] (Even today, 1 in 10 of all medical diagnoses are incorrect, according to the Society to Improve Diagnosis in Medicine [4]).

Even with widespread use of laboratory screening to confirm or rule out measles, correct diagnoses are not guaranteed, for two reasons:

  • Diagnostic bias promoted by health authorities. For example, the CDC advice to health professionals is “To minimize the problem of false positive laboratory results, it is important to restrict case investigation and laboratory tests to patients most likely to have measles”. Those “most likely” to have measles, of course, are the unvaccinated and those who’ve recently travelled abroad. This, of course, serves to reinforce the current paradigm that vaccination ‘works’ and measles has been eliminated from the US, and the only reason outbreaks still occur is because of travellers and the unvaccinated [5].
  • Laboratory testing is not guaranteed to be correct. The specimen needs to be collected at just the right time, and stored under the right conditions. According to the World Health Organization, dengue fever, chikungunya and zika viruses can also present with fever and rash…and test positive for measles – due to “non-specific reactions or formation of immune complexes that can produce a false positive IgM result in measles or rubella IgM assays [6].”

3. Vitamin A saves lives…but apparently is not as profitable as vaccines.

It has been known for decades that supplementing with Vitamin A substantially reduces mortality rates from infectious diseases in developing countries. In the case of measles, Vitamin A supplementation can halve the mortality rate [7].

In the early 1990’s, control of Vitamin A deficiency in developing nations was declared a major international goal, and lauded as possibly the most cost effective of all health interventions [8-9]. This is because sufficient levels of Vitamin A not only benefit overall health and immunity, but also prevent blindness. Why is it then, that decades later, a country like Rwanda has a 98-99% vaccination rate, but only 3% rate of Vitamin A supplementation [10]?

In developing countries, Vitamin A may be administered intravenously in hospitalized measles cases, but oral Vitamin A supplementation is not promoted for home use (which would potentially avert the need for hospitalisation) [11].

4. How the measles virus was supposedly ‘isolated’

The measles component in today’s vaccine was developed in 1954, by scientist John Enders. In a paper published by The American Journal of Public Health, Enders described how he did it [12]:

First, his team obtained ‘throat washings and blood’ from an 11-yo boy with measles named David Edmonston. When he added it to a specimen of ‘post-natal cells’ (cervical cord? Infant foreskin?), these cells fell ill. He assumed this was caused by the measles virus.

He then added the mixture to a culture of HeLa cells – human cervical cancer cells that are so aggressive, and so prolific, they have managed to contaminate many cell lines all over the world. The fluid that ran out, he poured onto a second culture of cells, and then a third, and so on, until he could see under microscope ‘giant multinuclear cells’. He attributed this to measles virus, not to aggressive cervical cancer cells.

He then passaged the fluid through human kidney cells numerous times, followed by numerous passages through human amnion cells, each passage undoubtedly creating more stress and mutations for the cells. When he injected the resulting fluid into monkeys, some got a ‘mild illness’ that in ‘some aspects’ resembled measles. This was all the proof Enders needed, that he had isolated the viral culprit causing illness in kids.

Enders decided using monkeys was too expensive, so went with chicken embryos to save costs, and today’s vaccine is still prepared on chicken eggs [13].

5. Measles Used to Treat Cancer

In 1973, the British Medical Journal published a case study, describing remission of infantile Hodgkin’s disease after natural measles infection [14]. The 23-month-old child developed measles, before radiotherapy could be started, and the researchers noted, “much to our surprise, the large cervical mass vanished without further therapy”.

In fact, vaccine-strain measles is currently being investigated as a potential treatment for cancer, with early results deemed as “promising”, with open trials still being conducted [15]. Earlier research stated that attenuated live measles virus demonstrated “propensity to preferentially infect, propagate in, and destroy cancerous tissue” [16]. 

It was explained that the reason for using modified viruses was “concerns regarding the potential of wild-type-viruses to cause serious side effects, technical limitations in manufacturing viral lots of high purity for clinical use, as well as the overwhelming excitement and fervent support the, at the time, newly emerging chemotherapy approaches that slowed down research on alternative strategies [17]”.

(Note also that a laboratory-engineered virus strain can be patented, which makes it much more desirable for drug companies).

In 2014, CNN aired the story of a woman with incurable multiple myeloma, who had already endured every type of chemotherapy available for that kind of cancer, two stem cell transplants, yet relapsed time and time again [18].

Scientists from the Mayo Clinic injected the woman with a genetically-engineered measles virus. The woman than experienced a high fever of 105, and vomiting (but declared it was the ‘easiest treatment’ she’d done by far). She went into remission for nine months, and then a small growth had to be removed surgically.

But was it the ‘measles’ virus that affected the cancer, or was it the purgative and cleansing action of the fever and vomiting – self-correcting mechanisms of the human body that are now largely suppressed through modern medicine?

In 1890, a young surgeon at New York City’s Memorial Hospital became dismayed at the frequent failures of surgery to treat cancer. His name was William Coley. He began to dig through the records of the hospital, and was intrigued to find the case of an immigrant dockworker, who was admitted to the hospital with a malignant tumour on his neck. He was later discharged without any treatment…and without any further sign of tumour on his neck [19].

William Coley tracked the man down, and found him in good health. It turned out that while the man was in hospital awaiting surgery, he developed a severe case of erysipelas, a painful red inflammation on the skin, accompanied by high fevers. The sarcoma on his neck vanished.

Coley began to experiment on those with inoperable cancers, by injecting bacterial endotoxins to produce a high fever, with an estimated cure rate of 60% (far surpasses the success rate of today’s treatment for stage 4 cancers). Note that the treatment was only successful if fever and skin eruption could be induced.

His product, Coley’s Toxins, was used all over the United States and Europe, but in the post-war years, when science and medicine were enthralled by the promise of ‘cutting edge’ technology such as radiation and chemotherapy, ‘fever therapy’ fell out of favour, and in 1962, Coley’s Toxins were banned by the Food and Drug Administration.

Ironically, ‘immunotherapy’ to treat cancer is now regarded as the ‘hottest area of cancer research’ [20]. Perhaps, if we looked at why people’s immune system had become so dysregulated to start with…?

Other random findings:

While still on the subject of measles, it would appear the current MMR vaccine was approved without having been tested in clinical trials, but rather, based on studies of the individual components.

The vaccine insert for the current MMR II vaccine references numerous studies, but they are ALL for the individual components of the vaccine, not the MMR vaccine [21].

There is one (small) study mentioned that appears to have been based on the MMR II vaccine but…no references are provided.

Clinical trials are generally conducted in phases of ever-increasing numbers of participants. Phase 1 trials usually involve 20-100 healthy volunteers. Phase II usually involves 100-300 volunteers from the target market. And phase III usually involves 300-3000 volunteers from the target market. So, we’d expect to see more than just one study referenced for a new vaccine.

A visit to Merck’s website leaves us none the wiser. The same small study is promoted, but still, puzzlingly, no references are given for said study [22].


Since being approved, more and more adverse reactions have become apparent [23]:

Additionally, Merck stopped making the single vaccines in 2009, so if one wanted to be vaccinated for ‘measles’, they must have the triple-antigen vaccine [24].

References:

 [1] Chen WJ. Comparison of LiST measles mortality model and WHO/IVB measles model. BMC Public Health. 2011;11 Suppl 3(Suppl 3):S33. Published 2011 Apr 13. doi:10.1186/1471-2458-11-S3-S33.

[2] Boulianne N, De Serres G, Duval B, Joly JR, Meyer F, Déry P, Alary M, Le Hénaff D, Thériault N. Département de santé communautaire, Centre Hospitalier de l’Université Laval. [Major measles epidemic in the region of Quebec despite a 99% vaccine coverage] [Article in French]. Can J Public health. 1991 May-Jun;82(3):189-90].

[3] Francombe H. Measles diagnosis unreliable, Australian Doctor, Feb 18, 2000.].

[4] Society to Improve Diagnosis in Medicine. Reducing Harm From Diagnostic Error, http://www.improvediagnosis.org/. Accessed October, 2017

[5] Centers for Disease Control and prevention, Manual for Surveillance of Vaccine-preventable Diseases: Measles, https://www.cdc.gov/vaccines/pubs/surv-manual/chpt07-measles.html. Accessed February, 2019.

[6] WHO, Manual for the Laboratory-based Surveillance of Measles, Rubella, and Congenital Rubella Syndrome, https://www.who.int/immunization/monitoring_surveillance/burden/laboratory/manual_section4.2/en/. Accessed February, 2019.

[7] SOMMER A. Vitamin A prophylaxis, Archives of Disease in Childhood 1997;77:191-194.

[8] World Bank. World development report 1993: investing in health. Washington DC: World Bank/New York: Oxford University Press, 1993.

[9] National strategies for overcoming micronutrient malnutrition. 45th World Health Assembly (agenda item 21), 1992. World Health Organisation, Geneva.

[10] UNICEF, Statistics: Rwanda, https://www.unicef.org/infobycountry/rwanda_statistics.html#114. Accessed September, 2017.

[11] Mayo Clinic, Measles: https://www.mayoclinic.org/diseases-conditions/measles/diagnosis-treatment/drc-20374862. Accessed February, 2019.

[12] Enders J et al, Measles Virus: A Summary of Experiments Concerned with Isolation, Properties and Behavior, Am J Pub Health, 1957, 47(3):275-282.

[13] CDC, Prevention of Measles, Rubella, Congenital Rubella Syndrome, and Mumps, 2013 Summary Recommendations of the Advisory Committee on Immunization Practices (ACIP), MMRW, 2013, 62(4), pp 8.

[14] Mota C. Infantile Hodgkins’ disease: remission after measles. BMJ, 1973; 2(5863): 421.

[15] Aref S, Bailey K, Fielding A. Measles to the Rescue: A Review Of Oncolytic Measles Virus. Viruses, 2016; 8(10):294.

[16] Msaouel P, Dispenzieri A, Galanis E. Clinical testing of engineered oncolytic measles virus strains in the treatment of cancer: An overview. Curr Opin Mol Ther, 2009, 11(1): 43-53.

[17] ibid

[18] CNN, Measles virus used to put woman’s cancer into remission, https://edition.cnn.com/2014/05/15/health/measles-cancer-remission/index.html. Accessed February, 2019.

[19] Engelking C, Germ of an Idea: Coley’s Cancer-Killing Toxins, Discover Magazine, http://discovermagazine.com/2016/april/11-germ-of-an-idea. Accessed February, 2019

[20] Ibid

[21] FDA, MMR II vaccine, https://www.fda.gov/downloads/BiologicsBloodVaccines/UCM123789.pdf. Accessed February 2, 2019.

[22] MerckVaccines.com, Seroconversion Rates, https://www.merckvaccines.com/products/mmr/seroconversion-rates. Accessed February, 2019.

[23] FDA, Measles, Mumps and Rubella Virus Vaccine, Live, https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094050.htm. Acessed February 2, 2019.

[24] CDC, Q&A’s About Monovalent MMR vaccines, https://www.cdc.gov/vaccines/hcp/clinical-resources/mmr-faq-12-17-08.html. Accessed February 2, 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

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[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.

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[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.

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