Select Committee on Health Minutes of Evidence

Memorandum by Mr David Thrower - continued

Improving Post-Licensing Clinical Studies

  274.  There would seem to be an overwhelming need for improved post-licensing studies to detect relatively adverse events, particularly as pre-licensing testing appears to involve relatively small numbers of children (MMR was quoted as being 10,000 children), and trials seem to have been excessively short in terms of the post-vaccination period studied (MMR was quoted as three weeks beyond vaccination).

  275.  Parents' concern at the need to improve post-licensing surveillance has also been expressed in the US:

    "Several speakers suggested conducting more focused, powerful, larger and better designed post-licensing clinical studies to detect serious rare adverse events of vaccines, that are not possible to detect in a clinical trial" (source: 1997 Institute of Medicine Vaccine Safety Forum proceedings, page 15);

  and, from the same source:

    "A consumer representative suggested that there be more government funding for studies designed to detect long-term adverse effects of vaccines or to identify individuals at high risk for adverse effects" (page 16).

  276.  It is interesting to note that US monitoring officials themselves take the view that a database of adverse reactions is too small to identify rare events, and that larger databases are necessary:

    "A CDC representative suggested that the large linked databases are best suited to identifying those at risk of adverse events following vaccination, once the association has been established. This individual believed that VAERS does not have the data necessary for a complete epidemiological study to assess risk factors." (source: 1997 Vaccine Safety Forum, page 17)

  277.  It is suggested that UK parents investigating their child's degeneration into autism, or other serious possible consequences of vaccination, would strongly desire such improved surveillance in the UK. There would be a cost involved, but there is already a huge financial cost associated with dealing with the present problem of autism, including care, education, respite and lost productivity, not to mention quality of life.

  278.  It is further suggested that studies be designed by the MCA in consultation with a wider professional community, including population statisticians, social service and education experts, and parents' groups and their representatives.

  279.  It is further suggested that testing of vaccines takes specific account of the risks for children that could be expected, on the basis of available research, to experience adverse events and outcomes. At present, such children may make up such a small proportion of the total number of children in a pre-licensing test that they are in effect excluded in terms of their influence on the outcome. This concern has been raised in the US:

    " . . . . Although children with genetic disorders or other chronic conditions represent between 5 and 15 per cent of all children (Warkany, 1971), the effects of vaccination on these children are not known because they were either excluded from, or not present in, large enough numbers in the studies that initially tested the effects of vaccines. (It was) suggested that researchers assess the risk of adverse events associated with vaccination in populations with specific genetic makeups"

    "Identifying families with several members who experience similar adverse events (or other associated health/hypersensitivity problems?) after vaccination . . . could provide a highly enriched sample of families suitable for studies of genetic factors associated with adverse events of vaccines" (source: 1997 Vaccine Safety Forum proceedings, page 33).

  280.  In the long term, the objective should be to be able to more closely identify risk factors, including issues such as:

    —  susceptibilty factors in particular children;

    —  risks associated with age;

    —  batch problems; and

    —  the issue of whether vaccines in combination are themselves a cause of increased risk.

Requirements for Manufacturers

  281.  The MCA has stated that there are statutory requirements on manufacturers:

    —  to provide information on their products to the MCA;

    —  to report all serious adverse drug reactions to their products within 15 days of receipt;

    —  to provide comprehensive safety updates covering all sources of data on safety at six-monthly intervals, for various intervals following authorisation; and

    —  to provide any information immediately, if this impacts upon the risks and benefits of their products.

  282.  However, it is not clear, despite these provisions, how compliance is checked and independently validated. This is a source of concern to parents. It also seems extremely unlikely that parents would report concerns to vaccine manufacturers.

  283.  The above makes a curious contrast with the MCA's views on the statutory reporting of adverse events as practised in France and in Sweden, where it is mandatory for physicians, unlike the UK yellow card system. In its letter of 21 August 1998, the MCA referred to:

    " . . . the difficulty of enforcement as there is no easy and systematic mechanism for identifying the reactions that doctors should have reported . . . In contrast, the statutory obligations placed on companies is based on a requirement for them to report adverse reactions".

  284.  It is unclear to parents as to why the MCA sees enforcement for a GP (an NHS employee) to report an adverse reaction as a problem, yet sees enforcement for free-standing manufacturers to report adverse reactions as not being a problem!

  285.  Also, it was stated by the Department of Health:

    "When a new component is added to established vaccines, manufacturers have to demonstrate that . . . there are no new acute adverse reactions, and that any recognised adverse reactions are not increased in frequency or severity" (source: letter from Immunisation and Communicable Disease Branch, 19 March 1998).

  286.  However, the Department does not explain how this reporting mechanism is being independently verified, nor what would occur (or not occur) if the adverse reactions were unrecognised, rather than recognised. The latter could include gradual degeneration into autism over a period of weeks/months after vaccination.

Batch Sizes

  287.  The MCA could also enable parents to make greater sense of adverse event statistics if these could be related to a standard batch size. At present, vaccine manufacturers do not have to conform to any particular standard batch size. Sizes of batches have been quoted as "5,000", "constantly variable", and "140,000".

  288.  These variations help to obscure an assessment by parents of risks, and as such, are an advantage to the manufacturers. There seems no reason why this advantage should continue to lie with the manufacturers, rather than the patients. It is therefore urged that vaccine batch sizes are standardised, say at 5,000 shots. There would seem no technical impediment to this, though no doubt there will be industry resistance to it. However, as it is the State that places the orders and makes the rules, the issue should be resolved by making it a condition, of tendering to supply vaccines to the NHS, that batch sizes are standardised.

MCA Position as at March 1999

  289.  A letter of 29 March 1999 confirmed that, on the autism/MMR issue:

    —  "the matter is still under review";

    —  "the MCA has sponsored a cohort study to determine the prevalence of autism before and after MMR vaccine availability". (Note: as my son initially degenerated following pre-MMR monovalent measles vaccination, the outcome of this study may need to be treated with circumspection);

    —  "the MCA has formed a working group of independent experts (the Agency does not explain how use of this term is precisely justified) which is conducting a detailed evaluation of reported cases of autism and closely related disorders and inflammatory bowel disease. This work is ongoing and information resulting from this will be made availabe in due course." (This was in response to a query as to the outcome over about 530 yellow card questionnaires that were filled out by parents with cases with Hodge Jones Allen, solicitors, and forwarded by the solicitors to the MCA to assist their investigations).

  290.  Given the crucial role of the MCA and its reporting mechanism, and the obvious close relationship it has with the Department of Health, whose own independence in the autism/vaccination issue has already been questioned, it would seem highly advisable that the MCA's statistical techniques and surveillance should be subject to audit through a wholly independent (of the Department and Agency) advisory group of academic personnel with a professional background in analysing population statistics and investigating patterns of reporting, including anecdotal reports.

  291.  Key conclusions: the MCA relies on surveillance systems which it has expressed satisfaction with, but which it has acknowledged there may be shortcomings in relation to the reporting of serious but relatively rare adverse events. Under-reporting is an acknowledged problem, but some of the measures being put forward to overcome under-reporting do not seem to address the autism/MMR under-reporting concerns. The MCA is now actively investigating the cases of some 530 of the children that are now with solicitors, and further developments are awaited. The Agency is committed to making the outcome of the review of cases public in due course, but any prolonged delay in this will be unacceptable to parents of the children affected. The MCA could also play a pivotal role in sorting out other problems, for example the constant variations in batch sizes.

  292.  Issues For Discussion:

    —  is the experiencing of severe delays in response a general one for parents?

    —  to what extent is the MCA not confronting the inadequacy of its surveillance?

    —  how can the statutory obligations upon pharmaceutical manufacturers to report problems be independently audited?

    —  how do the various mechanisms for identifying adverse reactions to vaccines relate to slow degeneration into autism, a condition which may take weeks/months to take effect, may take a further time to be fully identified, and which may take months/years to be properly diagnosed?

    —  how can additional statistical expertise be added to the MCA's primarily medically-based advice sources?

    —  should the statistically methodology of the MCA's reporting systems be subject to independent validation and regular audit?

    —  should degeneration into autism be made a recognised ADR in case it is connected with vaccination?

    —  what other mechanisms should be introduced to link the MCA database with autism detection?

    —  should the yellow card system be given statutory force?

    —  should the "polarity" of the yellow card system be reversed, in other words to positively require each case to be signed-off by the GP concerned three months afterwards as having had no adverse consequences?

    —  what recent improvements has the MCA made to yellow card that could be expected to pick up the autism degeneration issue?

    —  should the MCA be encouraged to actively seek out every single case of potential degeneration, to enlarge its database?

    —  should the MCA develop LLDBs (large databases) to improve all health surveillance?

  293.  Suggested Recommendations for Action:

    —  the response times of the MCA to parents require monitoring, and the results regularly publishing, as per Department of Health responses;

    —  the statutory obligations upon manufacturers need independent audit, preferably by an independent Health Regulator;

    —  the effectiveness of the MCA's surveillance methods also require audit, and it is essential that this is a wholly independent regulatory function. The MCA must not be judge of its own effectiveness. This should be part of a new independent Regulatory responsibility;

    —  greater independent statistical expertise needs to be brought to bear as part of the above;

    —  when there is a pattern of parents' reports alleging an adverse reaction, such as degeneration into autism, the alleged syndrome needs to be added to the MCA's recognised ADRs at the earliest opportunity, and advice circulated according, so that parental allegations can be actively investigated in the context of a more meaningful statistical base;

    —  the databases that are linked into the MCA yellow card database need widening. With computerisation, there seems no reason not to have an all-child database that the MCA can regularly review for suspected ADRs;

    —  the yellow card reporting system needs to be reversed, and replaced by a "green card" system where every child is positively cleared six months after vaccination, replacing the present "no news is good news" system. An early-ADR system would need to be retained for chronic urgent reactions; and

    —  degeneration into autism and other conditions needs to be built into any future reporting mechanism.


  294.  The Department of Health repeatedly seeks to attempt to reassure parents of children that have suffered an adverse consequence of vaccination that there are several bodies, such as the Joint Committee on Vaccination and Immunisation, and the Committee on Safety of Medicines, which, if there was any problem, would have identified it and acted upon it.

  295.  However, to parents, the Joint Committee on Vaccination and Immunisation in particular is a body that is secretive and lacks proper accountability. Its decisions lack transparency. The "accountability chain" between its members and the patient is extremely long, and potentially seriously flawed.

  296.  No effort seems to be made by the Department of Health to verifiably demonstrate to the public that committees such as the JCVI really are independent.

  To demonstrate this properly requires transparency. Generalised Departmental assurances are wholly insufficient.

  297.  It is understood that membership of the Joint Committee on Vaccination and Immunisation, and the Committee on Safety of Medicines, is subject to strict rules of secrecy. The proceedings and decisions of both bodies are confidential, and cannot be scrutinised by parents or agents acting on their child's behalf.

  298.  It is also understood that, in the event of any breach of confidentiality, an individual member of either Committee can be sued by pharmaceutical manufacturers or subject to other sanctions, and that there is no defence of public interest immunity to defend any individual member against litigation or prosecution.

  299.  This appears to place excessively great reliance on the infallibility and quality of decisions of these bodies. It also appears to give greater weight to the professional interests of the private sector and of the Department of Health and its agencies, compared with the interests of protecting vulnerable subsets of children. Also, the permitting of the destruction of vaccine records after just six years, far less than the timeframe of the Consumer Protection Act and the 21-year rule for child health records, is testimony to the lightness of regulation operated by these bodies.

  300.  There is also concern at how independent these two "independent" bodies are, given their critical role in relation to influencing Government and the public as to vaccine safety and possible links between vaccination and autism. For a key public body to be independent, it is suggested that:

    —  it should not be the case that individual members of these bodies, or any other relevant bodies, should have a direct financial interest in the manufacturers of products that are under the srutiny of these organisations, for example through personal or close-family shareholdings;

    —  there should not be frequent and direct transfer of employment of individuals between "the regulators" and "the regulated", particularly in the case of individuals moving from regulatory functions into private-sector organisations within the regulated sector. (This exchange of employment is sometimes referred to as "the revolving door", and could compromise the degree to which an individual acted against the financial interests of a private-sector provider, or in favour of greater openness or transparency to the benefit of patients);

    —  decisions, and minutes of meetings (barring the most limited-possible definition of commercially confidential material) should be published;

    —  registers of members' interests, including shareholdings and other obvious potential conflicts of interest, should be published on the Internet.

  301.  It is not clear that these principles are being upheld in practice, and press reports in April 1999 actually indicated that in the case of the first-mentioned, the exact reverse was the case (Insight Sunday Times, 4 April 1999). Parents investigating adverse outcomes to medical treatment should be able to expect a watertight partition between "the regulators" and "the regulated", and believe that this is not occurring at present. The Sunday Times confirmed that:

    —  a senior pharmacist on the CSM held shareholdings in Glaxo, SmithKline Beecham and other companies;

    —  the Chairman of the Standing Medical Advisory Committee (SMAC) held £130,000 shares in Glaxo and SmithKline Beecham;

    —  another member of SMAC had neglected to declare £15,000 of shares in drug companies.

  302.  Issues for Discussion:

    —  how can the accountability of the JCVI and CSM be very significantly improved?

    —  how can this accountability be made to work in a practical way for individual members of the public? Should all minutes and decisions be published, subject to exemption for the most limited number of specific issues?

    —  should public interest immunity be provided for JCVI and CSM members and their staffs?

    —  how can the present overriding concern of the JCVI/CSM for public confidence in vaccines be more properly balanced against the legitimate concerns of individual members of the public that their child may have been damaged?

    —  should all members of the JCVI/CSM and their support staffs, and employees of the MCA and relevant parts of the Department of Health, be debarred from holding shares in pharmaceuticals manufacturers?

    —  should members of the JCVI and CSM be debarred from future membership if they return to the pharmaceuticals industry in the meantime?

    —  how should issues such as offers from manufactuers for research funding be managed in order to avoid potentially compromising the actions of regulatory/Government personnel and committees?

  303.  Suggested Recommendations for Action:

    —  the decisions and minutes of the JCVI and the CSM should be open to public scutiny, subject to limited commercial-consideration protection only insofar as absolutely necessary. The minutes and decisions should be published on the Internet, and available upon request from members of the public;

    —  public interest immunity should be provided for members of the JCVI and CSM. Both bodies should include observer members from a new Office of the Health Regulator;

    —  members of the public with legitimate concerns regarding their children should be taken proper account of by the JCVI and the CSM. The law regarding the activities of these organisations and their need to properly balance the rights of individual children against the health needs of the community should be clarified and enforced through independent regulation;

    —  such regulation should not permit "wider health interests of the community" to be used as an unquantified blanket argument for disregarding cases of suspected damage. The benefits of community immunisation and the risks of identifiable individual damage should be properly weighed-up, and independently validated;

    —  all JCVI, CSM, Department of Health and other appropriate personnel and appointees should be debarred from themselves or their families holding shares in, or receipt of other benefits from, pharmaceutical manufacturers;

    —  a formal Code should be drawn up to discourage the "revolving door" whereby personnel freely and regularly move between "the regulators" and "the regulated", and this should become a condition of employment within the JCVI, CSM, etc; and

    —  a review should be undertaken of other financial support, and support in kind, from the pharmaceutical manufacturers to central government and the NHS, including academic research at hospitals and universities, to ensure that regulating functions are not compromised by financial-support considerations.


  304.  The Medical Research Council is an independent body which receives its grant aid from the Office of Science and Technology, which is part of the Department of Trade and Industry.

  305.  The Medical Research Council has been extremely helpful in answering inquiries from myself as a parent investigating their child's adverse outcome to medical treatment. It is understood to have formed a sub-group on research into inflammatory bowel disorders and autism.

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Prepared 27 July 1999