Grandinite

The following blog post is a respnse to Antonia Zerbisias’ recent column in the Toronto Star, H1N1 Causes Outbreak of Conspiracy Claptrap. I don’t blame anyone for getting the vaccine, because it’s probably the best defense against H1N1. Also, it would absolutely suck to travel somewhere on vacation, get H1N1, and spend days in quarantine, which is what happened to a friend of mine.

But there’s something I’ve noticed about the H1N1 vaccination debate, and it’s that people in both the for and against camps seem to believe their interpretation of “the truth” is “the truth” when, in many respects, both are right and both are wrong. You will probably not die from H1N1 any more than you will fail to develop some nasty side effects if you choose to get the vaccine.

I am not going to try to convince anyone not to get their H1N1 shot, but rather explain why I’m not getting mine.

1. Limited Clinical Data.

Health Canada admits there’s not much clinical data on the adjuvant in our vaccine: “There is currently limited clinical experience with Arepanrix™ H1N1, and limited clinical experience with an investigational formulation of another AS03-adjuvanted vaccine containing the same or a slightly higher amount of antigen derived from A/California/7/2009 (H1N1) (see section Pharmacodynamics) in healthy adults aged 18-60 years and no clinical experience yet in the elderly, in children or in adolescents. ”

Reading the Dosage & Administration section of Health Canada’s fact sheet, we find the following clinical data available (my translation/interpretation is in italics). It’s not encouraging.

Adults aged 18-60:

“preliminary immunogenicity data obtained at three weeks after administration of an investigational formulation of another AS03-adjuvanted H1N1 vaccine ”

Translation: Data were obtained in a 3-week follow-up using the same adjuvant, but with a different strain of influenza

Elderly (>60 years):
“No clinical data are available for Arepanrix™ H1N1 in this age group.”

Translation: none needed

Children and adolescents aged 10-17 years:
“No clinical data are available for any influenza vaccines with AS03 in this age group. Consideration may be given to dosing in accordance with recommendations for adults.”

Translation: We have no clinical data, but we think it’s the same as adults (we won’t find much three weeks after vaccination).

Children aged 3-9 years:
Based on limited clinical data available for AS03-adjuvanted H5N1 vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 in this age group, 0.25mL of vaccine (i.e. half of the adult dose) at an elected date and a second dose administered at least three weeks later may be considered sufficient. See section Pharmacodynamics.

Translation: If you give a child half a dose, and after three weeks she or he has some response, there’s no need to give the second dose. But it’s best to do a follow-up.

Children aged from 6-35 months:
No clinical data are available for influenza vaccines with AS03 in this age group. Consideration may be given to dosing in accordance with the recommendation in children aged 3-9 years.

Translation: We don’t really know, so just experiment with the dosage you gave to the older kids because we’re guessing the two groups are the same.

Children aged less than 6 months:

Vaccination is not currently recommended in this age group.

Mother’s breast milk is probably good enough, and kids this young aren’t usually vaccinated anyhow.

All told, the Canadian government admits the clinical data are lacking, but because it perceives the risk to population health to be so large, it is going full steam ahead, which brings me to my next reason.

2. H1N1 is no more fatal than the regular flu.
This is what astonishes me. If the odds of dying from H1N1 are so low, then why would the Canadian government fast track a vaccine on the basis of limited clinical data? The WHO changed the definition of a level six pandemic to a weaker criteria that eliminates necessary conditions of mortality factors. That’s like changing the definition of GDP to exclude one of its components: Consumption, Investment, Gov’t Spending, and Net Exports. Take one of those away, and you don’t have GDP any more. The WHO has weakened its criteria to exclude the mortality aspect. So the virus just has to infect a large number of people in greater than two countries simultaneously.

All mortality data on H1N1 is going to be suspect. We will only have data on hospitalization rates and deaths confirmed by lab tests, and no way of knowing the true infection rate, because H1N1 can’t be confirmed without lab testing. It is likely that most people who contract H1N1 will experience it as a “flu they’ve never felt before”, and odds are, they’ll survive. They won’t go to their doctor. If you call your general practitioner with “flu like symptoms”, you will most likely be diagnosed with H1N1 as a safety precaution. Because we can only estimate the population infection rate, it’s likely that the mortality rate of H1N1 will be over-estimated.

3. AS03 is not MF59.

When debating the adjuvants in the squalene-containing AS03 “adjuvant system”, people conflate the data on MF59 and AS03 on the basis that both contain squalene. For example, a person will object to Canada’s H1N1 vaccine on the basis that it contains squalene, and invariably, someone will cite the fact that 45 million people have been vaccinated in the EU with Focetria, a vaccine containing squalene, and the world hasn’t ended because of it. It seems that I’m being nitpicky here, because both contain squalene, but squalene shouldn’t be the point of debate. The debate should be about the difference between the MF59 adjuvant and the AS03 “adjuvant system. The former contains squalene, but has a substantial track record, whereas the latter, while it also has squalene, constitutes an “adjuvant system” with a much shorter history of 39,000 subjects.

The EMEA had this to say about the difference between MF59 (in this case, Focetria), and AS03 (in this case, Pandemrix/Arepanrix):

“The vaccines recommended for authorisation, Focetria and Pandemrix, contain ‘adjuvants’ (substances that enhance the immune response so that less viral material can be used in each dose of vaccine). They are widely used in vaccine manufacture and have a good safety record. The adjuvant in Focetria has been used in another flu vaccine since 1997 in more than 45 million doses. The adjuvant in Pandemrix has been tested in clinical trials involving several thousand subjects.
As with all medicines, rare adverse reactions may only be detected once the vaccines are used in large numbers of people. The Agency has requested that vaccine manufacturers implement plans to actively investigate and monitor the safety of vaccines as soon as they are used across the EU, so that action can be taken as early as possible if a safety issue emerges. As part of this, the manufacturers have committed to carry out post-authorisation safety studies in about 9,000 subjects for each vaccine.

This point alone tells me that while both MF59 and AS03 contain squalene, MF59 has a track record that’s a thousand times longer than AS03. I’m not convinced Health Canada has done its due diligence, which brings me to my final pont:

4. The Interim Order

In order to get GlaxoSmithKline’s AS03-adjuvated vaccine to market, Canada had to do the following:

1. Sign a contract 10 years ago (one that the Canadian people aren’t allowed to see).
2. Exempt GSK from all liability, and place the liability onto the taxpayer.
3. Issue an Interim Order that does the following:

i. Changes the definition of new drugs from:

Division 8
New Drugs
C.08.001. For the purposes of the Act and this Division, “new drug” means
(a) a drug that contains or consists of a substance, whether as an active or inactive ingredient, carrier, coating, excipient, menstruum or other component, that has not been sold as a drug in Canada for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that substance for use as a drug;
(b) a drug that is a combination of two or more drugs, with or without other ingredients, and that has not been sold in that combination or in the proportion in which those drugs are combined in that drug, for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that combination and proportion for use as a drug; or
(c) a drug, with respect to which the manufacturer prescribes, recommends, proposes or claims a use as a drug, or a condition of use as a drug, including dosage, route of administration, or duration of action and that has not been sold for that use or condition of use in Canada, for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that use or condition of use of that drug.

To:

Prohibition
C.05.003. Despite sections C.01.014, C.08.002 and C.08.003, no person shall sell or import a drug for the purposes of a clinical trial unless
(a) the person is authorized under this Division;
(b) the person complies with this Division and sections C.01.015, C.01.036, C.01.037 to C.01.040, C.01.040.2, C.01.064 to C.01.067, C.01.070, C.01.131, C.01.133 to C.01.136, and C.01.435; and
(c) if the drug is to be imported, the person has a representative in Canada who is responsible for the sale of the drug. (link to various sections of the act)

This is outlined in the Interim Order as follows:

3. (1) For the application of the Regulations with respect to the sale of the vaccine,

1. a reference to the prohibitions under section C.08.002 of the Regulations shall be read as a reference to the prohibitions under section 5;

What does all this language mean? Basically, that the vaccine (adjuvant) does not have an established track record, and may be allowed into Canada for the purpose of clinical trials if it meets the various subsections of the act. These acts pertain to:

C.01.015 – Tablet Disintegration Times
C.01.036 – Misc. (Nasal sprays, salts, etc)
C.01.037 – Salicylic acids
C.01.040 – chloroform and arsenic
C.01.040.2 – Colouring agents
C.01.064 – Preservatives (in this case Thimerosal)
C.01.067 – presence of pyrogens
C.01.070 – Dissolvability of tablets
C.01.131 – Aminopyrine and Dipyrone
C.01.133 – Exemptions regarding the above, specific to vets and pharmacists
C.01.136 – Tablets containing potassium salts
C.01.435 – Chloramphenicol

The only regulation that really applies is C.01.064. It seems to me that the AS03 vaccine was exempted from regulations pertaining to its track record as an “Adjuvant system” and is instead being allowed on a clinical basis, primarily because one of the ingredients in said adjuvant system (Thimerosal) are at a safe level. By that logic, I could drink a glassful of gasoline on the basis it has levels of lead deemed to be safe.

It’s right there in front of you: The AS03 adjuvant is allowed into Canada on the basis of being a clinical trial. The reason this had to be done? Because the so-called studies of the AS03 adjuvant do not establish a long enough track record. I won’t even get into how GSK is heavily involved in the writing and interpretation of the results of these studies. I’ll save that for another day. To re-state, these previous studies on AS03 were a trial run, and the real experiment has just begun. We are all swine flu guinea pigs.