Although, thanks to the pharmaceutical industry, physicians have the
privilege of pertaining to a profession including no less than 28% of
“consultants” 1 (most of the remaining operating as “investigators”,
“experts”, “opinion leaders” and all that sort of persons), thousands of
hours of work on the hepatitis B vaccination inclined me (in overall
accordance with some others 2) to the sad conclusion that a vast majority
of our colleagues are definitely unable to pass an autonomous judgement on
the quality of a study, whereas a vast majority of the remaining small
minority fails to do so most probably due to lack of time: while since its
public communiqué of Feb 2000, the French Agency (which is certainly not
suspect of excessive criticism against this vaccination, its producers or
their experts) has concluded that the results of a study by Zipp et al 3
should be no less than “rejected” due to failures some of them should be
obvious at first sight, eminent scholars in that field go on quoting it as
a relevant reference in the debate on the vaccine toxicity 4.
Therefore, I have tried to develop an original alternative to Evidence-
Based Medicine, namely an “Idiot’s Guide to Epidemiology” in reference to
the well-known series of books on computing. Let’s illustrate by an
example. Fifteen years ago, just prior to the French campaign of
vaccination against hepatitis B, a medical doctor like me (even practising
as a “consultant”, s’il vous plaît) could have never seen a patient with
multiple sclerosis (MS); today, ask any non health professional in France
– a butcher, a trader, a clerk, a lawyer, a concierge, a gardener, a rep
of a pharmaceutical firm: almost everybody knows one or several cases of
MS in people around him/her… This does not deserve a Nobel price to guess
than when a change in health environment is so dramatic, the most likely
cause may be the irruption of an exogenous factor – a drug, for example:
just recall the precedents of phocomelia after thalidomide introduction or
pulmonary hypertension with Aminorex®.
This democratic experience of a sharp increase in the frequency of MS may
be easily correlated with harder data: whereas the total number of French
MS was less to 30 000 according to the last assessment available prior to
the vaccination campaign 5, it was at least 60 000 in the first one
delivered after the campaign 6, and a number of sources (e.g. from
patients associations) give now figures close to 80 000-90 000.
Interestingly enough, the French health authority – which strongly
supported the vaccination campaign in 1994 – did not order any serious
investigation about such a frightening human, medical as well as
economical epidemics, contending itself with the vague argument that this
increase would simply be an artefact due to an increase in the accuracy of
diagnosis procedures… However, as due to media coverage concerning the
neurological hazard of hepatitis B vaccines, the requirement to make a
diagnosis of MS became stronger and stronger in France (several attacks,
positive RMI, etc.), it is clear that if the real frequency had been
stable, the assessed frequency should have decreased, and certainly not
increased…
So, let’s try a more reasonable explanation. In its public communiqués,
the French Agency always contended that if the neurological risk of
vaccination “could not be excluded, it was small” – an assessment, by the
way, which is notoriously devoid of any scientific meaning 7. Only in a
recent publication 8, tried some of its experts to be more precise about
this “smallness”, admitting that the relative risk should not be higher
than a 3-fold increase – by the way an assessment strangely parallel to
that by Hernan et al 9, and perfectly consistent with the assertion by the
main persons in charge of the epidemiological studies performed on behalf
of the French Agency who admitted that US as well as French data were
consistent with an “epidemiologically important increase in risk” 10. With
an recognized proportion of half of the French population exposed to
hepatitis B vaccination, a background noise of less than 30 000
spontaneous MS in the overall population should have led to about 15 000
expected cases in those exposed to this vaccination (30 000 * 0.5). A 3-
fold increase in risk (according to Hernan et al’s expectations 9
reluctantly confirmed by the experts of the French Agency 8 10) should
thus have led to an observed number of 15 000*3 = 45 000 cases of MS in
the vaccinated sub-population; added to the 15 000 expected cases in the
sub-population not exposed to the vaccine, this should account (according
to the “Idiot’s Guide for Arithmetic”) for a total of 60 000 cases (45 000
+ 15 000) after the vaccination campaign, as exactly reflected by the most
official estimates of French governmental experts 5 6, some of them
directly involved in re-assuring investigations on this vaccination 11.
Due to fluctuations in current estimates, potential excess up to a total
of 90 000 MS could obviously be ascribable to the additional fact that,
due to vaccination of health professionals – mandatory in its principle,
but unequal in its application towards lower socio-economical status
(nurses, nursing auxiliaries, cleaning ladies) of high female prevalence –
the “universal vaccination” has been relatively more frequent in the young
female population, where the baseline incidence of MS comes to its peak,
therefore accounting for an additional increase in the absolute number of
cases on the basis of a 3-fold increase in risk.
A small checking according to the elementary principles of arithmetic:
such a frightening surge in MS prevalence is perfectly consistent with
another admission by the governmental experts, namely that the number of
cases spontaneously reported after hepatitis B vaccination was higher than
the expected cases 12. Having regard to the known scale of underreporting
in France, this admission cannot be less than the confession of an
unprecedented drug-induced epidemic.
As compared to the UK, whose population is approximately the same as in
France but with a higher prevalence of expected MS, and having regard to
the failure of the “universal” campaign which failed to reach more than
half of the French population, it can be hypothesized that a successful
universal campaign in that country could, in the long term, account for a
minimum of 60 000 vaccination-induced MS (to say nothing about the others
hazards of this vaccination, such as lupus, myelitis, thyroid diseases,
chronic fatigue, amyotrophic lateral sclerosis, etc. 13). To discuss the
benefit/risk of “universal childhood immunisation”, these figures should
be put in perspective with the expected number of significant
complications of hepatitis B within the same country – esp. in non
migrants, where the disease is generally benign and self-limited. However,
I missed to find this baseline parameter in the BMA’s “call for universal
childhood immunisation in the UK” 14.
As we say on this side of the Channel: “c’est trop idiot !” (that’s so
silly)…
References
1. Campbell EG, Gruen RL, Mountford J, Miller LG, Cleary PD,
Blumenthal D. A National Survey of Physician-Industry Relationships. N
Engl J Med 2007; 356:1742-50.
2. Anon. Doctors and medical statistics. Lancet 2007; 370:910.
3. Zipp F, Weil JG, Einhaupl KM. No increase in demyelinating
diseases after hepatitis B vaccination. Nat Med 1999; 5:964-5.
4. Hernan MA, Jick SS. Hepatitis B vaccination and multiple
sclerosis: the jury is still out. Pharmacoepidemiol Drug Saf 2006; 15:653-
5.
5. Delasnerie-Laupretre N, Alperovitch A. Epidémiologie de la
sclérose en plaques. Rev Prat 1991; 41:1884-7.
6. Confavreux C, Ginoux L. Scléroses en plaques. Rev Prat 2002;
52:529-37.
7. Nakao MA, Axelrod S. Numbers are better than words. Verbal
specifications of frequency have no place in medicine. Am J Med 1983;
74:1061-5.
8. Hanslik T, Valleron AJ, Flahault A. [Risk-benefit assessment of
hepatitis B vaccination in France, 2006]. Rev Med Interne 2006; 27:40-5.
9. Hernan M, Jick S, Olek M, Jick H. Recombinant hepatitis B vaccine
and the risk of multiple sclerosis. A prospective study. Neurology 2004;
63:838-42.
10. Begaud B, Alperovitch A. Vaccinations and multiple sclerosis. N
Engl J Med 2001; 344:1793.
11. Confavreux C, Suissa S, Saddier P, Bourdes V, Vukusic S.
Vaccinations and the risk of relapse in multiple sclerosis. N Engl J Med
2001; 344:319-26.
12. Fourrier A, Begaud B, Alperovitch A et al. Hepatitis B vaccine
and first episodes of central nervous system demyelinating disorders: a
comparison between reported and expected number of cases. Br J Clin
Pharmacol 2001; 51:489-90.
13. Girard M. Autoimmune hazards of hepatitis B vaccine. Autoimmun
Rev 2005; 4:96-100.
14. Pollard AJ. Hepatitis B vaccination. BMJ: BMJ 2007; 335:950.
Competing interests:
Dr Girard really works as an independent “consultant” for the pharmaceutical industry, including (at least until recently) hepatitis B vaccine manufacturers and a number of their competitors.
Rapid Response:
Being or not being an idiot
Although, thanks to the pharmaceutical industry, physicians have the
privilege of pertaining to a profession including no less than 28% of
“consultants” 1 (most of the remaining operating as “investigators”,
“experts”, “opinion leaders” and all that sort of persons), thousands of
hours of work on the hepatitis B vaccination inclined me (in overall
accordance with some others 2) to the sad conclusion that a vast majority
of our colleagues are definitely unable to pass an autonomous judgement on
the quality of a study, whereas a vast majority of the remaining small
minority fails to do so most probably due to lack of time: while since its
public communiqué of Feb 2000, the French Agency (which is certainly not
suspect of excessive criticism against this vaccination, its producers or
their experts) has concluded that the results of a study by Zipp et al 3
should be no less than “rejected” due to failures some of them should be
obvious at first sight, eminent scholars in that field go on quoting it as
a relevant reference in the debate on the vaccine toxicity 4.
Therefore, I have tried to develop an original alternative to Evidence-
Based Medicine, namely an “Idiot’s Guide to Epidemiology” in reference to
the well-known series of books on computing. Let’s illustrate by an
example. Fifteen years ago, just prior to the French campaign of
vaccination against hepatitis B, a medical doctor like me (even practising
as a “consultant”, s’il vous plaît) could have never seen a patient with
multiple sclerosis (MS); today, ask any non health professional in France
– a butcher, a trader, a clerk, a lawyer, a concierge, a gardener, a rep
of a pharmaceutical firm: almost everybody knows one or several cases of
MS in people around him/her… This does not deserve a Nobel price to guess
than when a change in health environment is so dramatic, the most likely
cause may be the irruption of an exogenous factor – a drug, for example:
just recall the precedents of phocomelia after thalidomide introduction or
pulmonary hypertension with Aminorex®.
This democratic experience of a sharp increase in the frequency of MS may
be easily correlated with harder data: whereas the total number of French
MS was less to 30 000 according to the last assessment available prior to
the vaccination campaign 5, it was at least 60 000 in the first one
delivered after the campaign 6, and a number of sources (e.g. from
patients associations) give now figures close to 80 000-90 000.
Interestingly enough, the French health authority – which strongly
supported the vaccination campaign in 1994 – did not order any serious
investigation about such a frightening human, medical as well as
economical epidemics, contending itself with the vague argument that this
increase would simply be an artefact due to an increase in the accuracy of
diagnosis procedures… However, as due to media coverage concerning the
neurological hazard of hepatitis B vaccines, the requirement to make a
diagnosis of MS became stronger and stronger in France (several attacks,
positive RMI, etc.), it is clear that if the real frequency had been
stable, the assessed frequency should have decreased, and certainly not
increased…
So, let’s try a more reasonable explanation. In its public communiqués,
the French Agency always contended that if the neurological risk of
vaccination “could not be excluded, it was small” – an assessment, by the
way, which is notoriously devoid of any scientific meaning 7. Only in a
recent publication 8, tried some of its experts to be more precise about
this “smallness”, admitting that the relative risk should not be higher
than a 3-fold increase – by the way an assessment strangely parallel to
that by Hernan et al 9, and perfectly consistent with the assertion by the
main persons in charge of the epidemiological studies performed on behalf
of the French Agency who admitted that US as well as French data were
consistent with an “epidemiologically important increase in risk” 10. With
an recognized proportion of half of the French population exposed to
hepatitis B vaccination, a background noise of less than 30 000
spontaneous MS in the overall population should have led to about 15 000
expected cases in those exposed to this vaccination (30 000 * 0.5). A 3-
fold increase in risk (according to Hernan et al’s expectations 9
reluctantly confirmed by the experts of the French Agency 8 10) should
thus have led to an observed number of 15 000*3 = 45 000 cases of MS in
the vaccinated sub-population; added to the 15 000 expected cases in the
sub-population not exposed to the vaccine, this should account (according
to the “Idiot’s Guide for Arithmetic”) for a total of 60 000 cases (45 000
+ 15 000) after the vaccination campaign, as exactly reflected by the most
official estimates of French governmental experts 5 6, some of them
directly involved in re-assuring investigations on this vaccination 11.
Due to fluctuations in current estimates, potential excess up to a total
of 90 000 MS could obviously be ascribable to the additional fact that,
due to vaccination of health professionals – mandatory in its principle,
but unequal in its application towards lower socio-economical status
(nurses, nursing auxiliaries, cleaning ladies) of high female prevalence –
the “universal vaccination” has been relatively more frequent in the young
female population, where the baseline incidence of MS comes to its peak,
therefore accounting for an additional increase in the absolute number of
cases on the basis of a 3-fold increase in risk.
A small checking according to the elementary principles of arithmetic:
such a frightening surge in MS prevalence is perfectly consistent with
another admission by the governmental experts, namely that the number of
cases spontaneously reported after hepatitis B vaccination was higher than
the expected cases 12. Having regard to the known scale of underreporting
in France, this admission cannot be less than the confession of an
unprecedented drug-induced epidemic.
As compared to the UK, whose population is approximately the same as in
France but with a higher prevalence of expected MS, and having regard to
the failure of the “universal” campaign which failed to reach more than
half of the French population, it can be hypothesized that a successful
universal campaign in that country could, in the long term, account for a
minimum of 60 000 vaccination-induced MS (to say nothing about the others
hazards of this vaccination, such as lupus, myelitis, thyroid diseases,
chronic fatigue, amyotrophic lateral sclerosis, etc. 13). To discuss the
benefit/risk of “universal childhood immunisation”, these figures should
be put in perspective with the expected number of significant
complications of hepatitis B within the same country – esp. in non
migrants, where the disease is generally benign and self-limited. However,
I missed to find this baseline parameter in the BMA’s “call for universal
childhood immunisation in the UK” 14.
As we say on this side of the Channel: “c’est trop idiot !” (that’s so
silly)…
References
1. Campbell EG, Gruen RL, Mountford J, Miller LG, Cleary PD,
Blumenthal D. A National Survey of Physician-Industry Relationships. N
Engl J Med 2007; 356:1742-50.
2. Anon. Doctors and medical statistics. Lancet 2007; 370:910.
3. Zipp F, Weil JG, Einhaupl KM. No increase in demyelinating
diseases after hepatitis B vaccination. Nat Med 1999; 5:964-5.
4. Hernan MA, Jick SS. Hepatitis B vaccination and multiple
sclerosis: the jury is still out. Pharmacoepidemiol Drug Saf 2006; 15:653-
5.
5. Delasnerie-Laupretre N, Alperovitch A. Epidémiologie de la
sclérose en plaques. Rev Prat 1991; 41:1884-7.
6. Confavreux C, Ginoux L. Scléroses en plaques. Rev Prat 2002;
52:529-37.
7. Nakao MA, Axelrod S. Numbers are better than words. Verbal
specifications of frequency have no place in medicine. Am J Med 1983;
74:1061-5.
8. Hanslik T, Valleron AJ, Flahault A. [Risk-benefit assessment of
hepatitis B vaccination in France, 2006]. Rev Med Interne 2006; 27:40-5.
9. Hernan M, Jick S, Olek M, Jick H. Recombinant hepatitis B vaccine
and the risk of multiple sclerosis. A prospective study. Neurology 2004;
63:838-42.
10. Begaud B, Alperovitch A. Vaccinations and multiple sclerosis. N
Engl J Med 2001; 344:1793.
11. Confavreux C, Suissa S, Saddier P, Bourdes V, Vukusic S.
Vaccinations and the risk of relapse in multiple sclerosis. N Engl J Med
2001; 344:319-26.
12. Fourrier A, Begaud B, Alperovitch A et al. Hepatitis B vaccine
and first episodes of central nervous system demyelinating disorders: a
comparison between reported and expected number of cases. Br J Clin
Pharmacol 2001; 51:489-90.
13. Girard M. Autoimmune hazards of hepatitis B vaccine. Autoimmun
Rev 2005; 4:96-100.
14. Pollard AJ. Hepatitis B vaccination. BMJ: BMJ 2007; 335:950.
Competing interests:
Dr Girard really works as an independent “consultant” for the pharmaceutical industry, including (at least until recently) hepatitis B vaccine manufacturers and a number of their competitors.
Competing interests: No competing interests