Memorandum by Mr David Thrower - continued
Yellow Card Reports
227. Under the yellow card scheme:
". . . doctors, dentists, hospital pharmacists
and coroners are asked to provide details of suspectedNOT
NECESSARILY PROVENADRs they encounter during their regular
work. For established drugs, report only serious reactions".
(source: Committee on Safety of Medicines factsheet, 1998, their
228. There is a Sub-Committee on Pharmacovigilance
(SCOP), which meets every two months and which advises the main
committee on the safety and risk/benefit considerations relating
to vaccines and other medicines. The Committee has eight members
with appropriate specialist medical backgrounds, but there is
concern by parents that they may lack sufficient specialist expertise
in statistical methodology in their original in-the-field data-collection,
and may have taken insufficient measures to search-out cases of
suspected degeneration, because degeneration into autism was not
recognised as potentially connected with vaccination.
229. There seems to be a contradictory attitude
within the MCA towards the yellow card system:
"The yellow card system . . . has a proven
record in quickly identifying new safety concerns" (letter
of MCA of 18 June 1998).
"The yellow card system is well established
and has been shown to be effective in identifying previously unrecognised
adverse drug reactions" (letter of MCA of 21 August 1998).
"The level of under-reporting varies with
the condition being reported . . . For very serious events
which are caused by a medicine, then our evidence suggests that
under-reporting will be much less" (my emphasis. Letter
of MCA of 21 August 1998).
230. But then, apparently in direct contradiction:
"In most situations there is considerable
under-reporting of reactions. It has been estimated from various
surveys that only 10-15 per cent of serious ADRs are reported"
(my emphasis. Source: Adverse Drug Reaction Information Service;
Guidance On Interpretation Of Yellow Card Data, published by the
Committee On Safety Of Medicines and the Medicines Control Agency,
"Spontaneous reporting systems such as the
UK yellow card scheme provide a major data source . . . (but)
. . . it is accepted that spontaneous reporting schemes have limitations,
including the level of under-reporting)". (Letter of MCA
of 29 March 1999.)
and perhaps even more significantly:
"In our whole database . . . autism has
been very rarely reported as an adverse drug reaction . . . These
figures are unsurprising since autism is not a recognised ADR
to any particular medicinal substance" (letter of MCA of
29 March 1999, my emphasis).
"Evidence from the yellow card scheme is
unlikely to resolve the issue as to whether or not autism could
be causally associated with MMR vaccine" (letter of MCA of
29 March 1999).
231. An indication that the level of under-reporting
of adverse drug reactions could be extremely high, even higher
than is being acknowledged by the Medicines Control Agency and
the Committee on Safety of Medicines, is provided by the West
Midlands Centre for Adverse Drug Reactions Reporting. The West
Midlands Centre has reported:
"A recent survey from a major teaching hospital
in Oxford gives a clearer idea of the proportion of adverse reactions
seen on the general medical wards and reported to the CSM . .
. 1,420 adverse reactions were collected from 20,695 consecutive
admissions, a rate of 60 per 1,000 admissions. Of these, 477 would
have fulfilled the CSM criteria for reporting, but only 30 yellow
cards seem to have been sent, accounting for only 6.3 per cent
of the identified `reportable' reactions"
232. The West Midlands Centre offers three
possible explanations for this extremely poor rate:
the reporter has not proved the relationship
between drug and reaction;
the reaction is not severe enough;
the reaction is already well known,
even when severe; and is therefore not "news".
233. It is suggested here that the first-mentioned
could be particularly important when applied to degeneration into
the Department is actively attempting
to persuade doctors that there is not a relationship (though this
paradoxically could alert them to the possibility of one);
many parents would not suspect a
relationship, though this is now changing;
some doctors will be anxious not
to be "taking on" their Department and Chief Medical
Officer over the degeneration issue; and
degeneration could be spread over
successive weeks/months, and thus be missed altogether.
234. The extremely low level of reporting
is also backed up by a study based upon the whole UK yellow card
database (Belton et al, Journal of Clinical Pharmacology 1995,
39, 223-6). This found that in any one year, 11-13 per cent of
all UK doctors sent in at least one yellow card. The study estimated
that about 60 per cent of all doctors would report at some stage
in their working lives.
235. But turning these statistics around,
it seems remarkable that in any one year 87-89 per cent of doctors
do not put in a single yellow card report, and, even more remarkably,
that it is estimated that 40 per cent of doctors would not expect
to submit any yellow cards throughout their entire working lives.
This could theoretically imply that almost all medicines are totally
safe, but alternatively, it is also possible to conclude, that
many parents do, that the yellow card system is extraordinarily
ineffectivea viewpoint clearly endorsed by the West Midlands
figures quoted above.
236. Also it is interesting to note that,
in the United States, the view is:
"Accumulations of events reported to a passive
surveillance system do not allow incidence rate calculations,
due to the generally unknown extent of under-reporting . . . On
the basis of VAERS data alone, we don't have proof that vaccines
are not contributing to these problems and we certainly don't
have proof that they are contributing" (source: Caveats to
the Interpretation of VAERS Data, Center for Biologics Evaluation
and Research, Vaccine Adverse Event Reporting System (VAERS),
1998, my emphasis).
Other Warning Mechanisms That Miss Autism
237. Correspondence has revealed that the
MCA appears to be placing faith in other auxiliary mechanisms
that do not seem likely to identify autism as a potential serious
adverse effect of vaccination for a minority of individual children.
"It is accepted that spontaneous reporting
schemes have limitations, including the level of under-reporting.
For this reason the MCA employs a variety of other data sources
. . . For example, the MCA also monitors the safety of medicines
through . . . a number of world-wide data bases. There are two
large computerised GP databases in the UK which are used by the
MCA routinely to evaluate drug safety concerns." (source:
letter of MCA of 29 March 1999).
238. However, the above does not address
the obvious criticism, that GP databases are highly unlikely to
contain details of slow degeneration into autism following vaccination,
and that once again, the MCA may not be able to grasp the numerous
cases of degeneration that may have occurred, because its systems
are pointing at (in the context of autism) the wrong database
239. The MCA has also pointed to improvements
to the yellow card adverse reaction reporting system. However,
the improvements that it cited in its letter of 29 March 1999
the extension of the yellow card
scheme to hospital pharmacists;
collaboration with GP prescribing
pilot projects to extend the scheme
to community pharmacists and nurses.
240. None of the above would have substantive
relevance to the detection of any increased incidence of autism.
241. The limitations of the pharmacist scheme
were again pinpointed by the West Midlands Centre for Adverse
Drug Reaction Reporting, in September 1997:
"Reporting By PharmacistsA Slow Start
. . . all registered hospital pharmacists (but not pre-registration
pharmacists) and community pharmacists in this Region can report
adverse reactions to CSM West Midlands providing they are directly
involved in the care of the patient" (their emphasis).
242. As hospital or indeed any other pharmacists
are unlikely to have any involvement in the care of autistic children,
it is not obvious how this measure relates to detecting degeneration
into autism in the weeks and months following vaccination, nor
to associated gut and food hypersensitivity problems. Once again,
it appears to be missing the autism-degeneration or autistic-enterocolitis
target, though no doubt it is a sensible measure in relation to
other health conditions.
243. If the above are the most quotable
improvements on offer, it implies that the yellow card scheme
is still missing autism, and that measures to amend it to pick
up autism as an ADR to vaccination have yet to be taken. If post-vacine
degeneration into autism continues to not be recognised as connected
with vaccination, then minor improvements to the yellow card scheme
will have no impact whatever.
Actual Yellow Card Figures
244. The yellow card system has produced
figures for measles/MMR vaccine adverse reaction reports that,
at first glance, seem to suggest that adverse reports are low,
and that very few children are affected.
245. However, if the numbers of reports
are a reflection of the level of under-reporting quoted (all types
of report) by the MCA and the CSM in their literature, then the
figures are rather more disturbing.
246. In 1988-97, some 3,029 reports were
received by the MCA for MMR (each report relates to one child,
but can include more than one specific reaction, and the receipt
of a report does not conclusively provide evidence that it was
linked to vaccination). Over the nine and a quarter years 1988-97,
3,029 reports relates to eight million children approximately,
giving a report receipt rate of 1 in 2,645 approximately.
247. However, if under-reporting is running
at 10 per cent to 15 per cent of total suspected instances, as
indicated by the MCA/CSM (admittedly an overall, all-reaction,
non-MMR-specific quote), then the 1 in 2,645 adverse report rate
could potentially be up to 10 times higher, or up to 1 in 265.
248. Some of the above could be reports
relating to very minor reactions. However, even the above could
overall be an underestimate. Degeneration into autism may have
been missed altogether, because it may have taken place gradually
over weeks or months, and because symptoms such as language loss
and acquired hyperactivity almost certainly would not have been
connected by parents as potentially linked to vaccination. In
my son's case, it was almost a decade before the connection was
made and an adverse reaction report filed.
249. The MCA has also confirmed (letter
of 18 June 1998) that it monitors medicines, including vaccination,
evaluation of a variety of epidemiological
published and unpublished literature;
a number of worldwide databases;
two large computerised GP databases
in the UK.
250. However, it would appear that few or
any of the above will have picked up degeneration into autism
after vaccination, or alerted the MCA to it, with the possible
exception of certain literature.
251. Experience indicates that the MCA is
not always in possession of all the relevant research literature.
As for studies, the problem there is that they have not been done.
It seems unwise to depend upon studies when none have been commissioned.
252. The MCA has pointed to its "new
method", developed by Dr Paddy Farrington (a statistician
at the Open University) and others, as a way of obtaining a good
estimate of whether a particular adverse event occurs more frequently
immediately after a vaccination than it does prior to a vaccination.
The method requires known vaccination histories for all those
children who are believed to be affected by a particular adverse
event, whether associated with a vaccine or not. The "new
method" uses separate databases, for hospital admissions
for serious events and for vaccination records, to do this.
253. However, a serious potential flaw may
be what is defined as "immediately after". If the Farrington
method defines "immediately after" as up to six months,
then it may detect a few cases of degeneration into autism. However,
even that would depend on the child appearing on a database during
that period, which may (given the time taken for paediatricians
to assess and diagnose children) be extremely unlikely. Many children
are not formally diagnosed for several years, or even at all.
Failure to Contact Families
254. It is a source of great surprise to
parents such as myself that the MCA does not closely investigate
the health background of families of children who have degenerated
into autism, to see if there is a pattern of background circumstances
that could help to provide a focus for future investigation, and
255. In the case of Oliver Thrower, a "yellow
card" report was filled out by the GP, and then no further
contact made. No direct contact at all was made with members of
the extended family of Oliver Thrower, although his GP was contacted
and his own individual case was added to ADR figures for the year
he was immunised.
256. Despite the above case, and other cases,
the MCA clearly has adopted the viewpoint of the Department of
Health, under which it is controlled for overall management purposes,
that there is no link between vaccination and autism, based upon
the seminar of March 1998. However, as it is believed that no
actual evidence was presented to the seminar, the seminar's conclusion
that there was no evidence was unsurprising, and the MCA's reliance
on this conclusion may prove in time to have been misplaced.
257. What is interesting, to parents seeking
investigation as to how their child degenerated into autism following
vaccination, is that the MCA's various safety-nets do not appear,
even in combination, to be focused upon the vaccine/autism issue.
This, and the past failure to recognise degeneration into autism
as an ADR, and the shortness of timespan for ADRs to apparently
be required to fall in, may explain how the entire syndrome may
have come to have been missed.
Failure to Actively Seek Out Potential Cases
258. It is also disturbing to parents seeking
an investigation of their child's degeneration that the MCA is
not actively seeking out details of every single potential case
of vaccine damage, as is being done in the reasonably comparable
instance of suspected Gulf War Syndrome.
259. The MCA has explained its policy of
not following up all the reported cases on a proactive basis as
"Suspected ADRs reported in association
with vaccines may not necessarily mean `vaccine damage' because
causation remains unproven. Reports range in seriousness from
minor symptoms such as nausea or fainting to serious neurological
reactions such as encephalitis. Following receipt of every yellow
card, a letter is sent to the reporter reminding them to forward
any further relevant information when available. Each yellow card
is evaluated by experienced assessors within the MCA with a focus
on following up serious cases, those for which more information
is needed to allow for a full assessment, and those which are
not recognised ADRs". (full text of response to this question:
source: letter of MCA of 29 March 1999.)
260. The above, which has not properly addressed
the original question in the correspondence, begs several questions:
how does this approach, of only reacting
to yellow cards, deal with parents' anecdotal cases?
how does it deal with cases of autism
following vaccination where the parents have not connected the
two events, but where the one followed on from the other?
how does this approach, of only reacting
to yellow cards, compare with the approach with GWS suspected
victims, where it is understood that every GP has been approached
on a cold-canvas basis in the search for potential cases?
as the MCA itself has already stated
the view that autism is not a recognised ADR, then the following
up of yellow cards presumably treats these children as having
experienced an unconnected event.
261. The above could be expected to severely
depress the MCA's figures. The MCA quoted figures on autism/ADR
as at 29 March 1999 as:
12 drug substances cited;
29 of the 37 associated with MMR.
262. At present, there appears to be some
suggestion of a culture of "no news is good news", with
the results that statistics on adverse reactions are minimised.
This may lead to a "circular argument of self-resassurance":
this implies that there are few problems;
because there are "few"
problems, the Agency does not need to proactively seek out cases;
because the Agency does not seek
out cases, statistics are low.
263. The lack of proactive searching-out
of autism cases therefore appears to place the MCA in a chicken-and-egg
trap, whereby it does not identify a problem because of the lack
of reports, and it does not seek the reports because it has not
identified that there is a problem. This is extremely disturbing.
264. The MCA does acknowledge that:
"Despite pre-marketing trials to establish
the safety and efficacy of a medicine, some drug safety hazards
will only emerge after widespread use of the medicine in clinical
practice. . .This is particularly true for rare adverse drug reactions"
(source: letter of MCA of 29 March 1999).
265. This implies that the MCA requires
a very large scale detailed database on autism and other forms
of sudden degeneration to be able to identify whether autism
and vaccination are causally as well as temporally linked.
Large Linked Databases
266. The need for large linked databases
(LLDBs) was recently acknowledged by the US Institute of Medicine
in the publication Vaccine Safety Forum: Summaries of Two Workshops,
National Academy Press, Washington DC, 1997:
To improve detection of adverse events associated
with vaccination. . .CDC established LLDB in 1990. This database
is a CDC-coordinated linkage of large databases of four large
health maintenance organisations. Comprising automated data from
more than 500,000 children aged 0 to 6 years in Oregon, Washington
and California, LLDB enables researchers to link vaccine exposures
to medical outcomes and thereby to estimate the rates of occurrence
of adverse events following vaccination. . An elevated rate following
vaccination, in comparison with a rate at other times, would suggest
a possible causal relationship to vaccination."
267. The absence of such a database in the
UK to date must leave the Department of Health's present publicly-stated
conclusion, that there is no link, open to question in the minds
of parents seeking the investigation of their child's condition.
268. It should also be pointed out that
even in the case of the US LLDBs cited above, parents are concerned
that the criteria for qualifying as a possible adverse event are
so tightly drawn as to exclude many potential adverse reactions.
This may be particularly important in the instance of autism,
where degeneration may be gradual over a period of several weeks.
269. There are many areas where the MC could
become more proactive, and actually seek out improved data, and
cases of possible damage.
270. Concern by parents on these issues
is not limited to the UK. At the Vaccine Safety Forum hosted by
the US Institute of Medicine in Washington DC in 1997, the published
report of the proceedings noted:
"A parent noted that no government representative
had ever contacted him personally seeking more information about
his son's death following vaccination with hepatitis B" (the
death had also been misclassified in the US adverse event reporting
system, as Sudden Infant Death Syndrome).
271. The parents themselves could be brought
into the system, again as noted at the US 1997 Vaccine Safety
"Noting that most paediatricians lack the
time to fill out long forms, a physician suggested that the number
of reports . . . could be increased by placing the burden of such
reporting on the parents of vaccinated children".
272. A criticism of the US vaccination adverse
event reporting system (VAERS) has been that its data is not easily
accessible either to the medical and research establishment or
to the public, with parents having to use the US Freedom of Information
Act to gain access to it. In the UK, there seems to be availability
of information from the MCA on demand, but this could be readily
improved by its being posted on the Internet, so that parents
can interrogate it from their homes. It is suggested that this
273. Publicly releasable information should
also be put out in a more user-friendly and self-explanatory form,
including graphs and indications of estimated true levels, allowing
for known under-reporting. The MCA could work with parents' groups
to develop an acceptable format. This would then help parents
to make an informed choice.