The proceedings of a conference on CJD and blood transfusions in Ottawa a few months ago

Health Canada Health Protection Branch - Laboratory Centre for Disease Control - Bureau of Infectious Diseases

Creutzfeldt-Jakob Disease, Decision-Making in Times of Uncertainty June 5-6, 1996, Crowne Plaza, Toronto

Risk Assessment Session, Chaired by Dr. Neil Cashman

Dr. Paul Brown, National Institute of Health

Dr. Brown reviewed the epidemiology of Creutzfeldt-Jakob Disease (CJD) internationally, describing the rare occurrence (1 per million population per annum), age at onset (median 60 years) and the clinical presentation. He described the unremitting progression and lack of instances of recovery. Among the sole recent findings of clinical importance in CJD has been the recent development of a possible spinal fluid confirmatory test from the National Institute of Health. The neuropathology was briefly described and information about the three major types of CJD was provided (familial, iatrogenic and sporadic). Information distinguishing certain clinical features or each type was provided.

Laboratory experiments have provided important information regarding which tissues are infectious - brain, spinal cord, CSF, eye and some peripheral tissues (lung, kidney, lymph nodes, liver, and spleen). Primate experiments have failed to find infectivity in blood, leukocytes, bone marrow, peripheral nerves, skeletal muscle, fat or milk. Neither milk nor meat have been found to have infectivity in any animal model. Dr. Brown reviewed, using summary slides, all current published literature concerning transmission of CJD to a variety of animals, and concerning transmission of other transmissible spongiform encephalopathies (TSE) to other animals. He provided constructive information regarding the limitations of each experiment, such as the lack of control animals, lack of reproducibility of some experiments and the small number of animals used in some experiments. Dr. Brown described experiments which have been initiated in NIH which are anticipated to provide some information to assist in decision making regarding blood transmission of CJD. Results from these studies may be available as soon as one year, although some will require up to three years. Dr. Brown concluded by saying that there was some level of infectivity in blood, but that infectivity was present only irregularly and in very low amounts. He stated that he "can accept that infectivity is in blood, probably in white cells, as a protein".


Dr. David Asher, Food and Drug Administration

Dr. Asher provided infectious diseases information which clarified the role and usefulness of animal experiments in the determination of infectivity of human pathogens. He reviewed the historical development of scientific knowledge regarding TSE, including a brief review of scrapie and the discovery of kuru in the 1960's. He described the first evidence of transmissibility of kuru, including information about chimpanzee transmissions. He noted that in many areas of infectious disease investigation, cell cultures have replaced animal experiments, however, no cell culture substitute has been validated for CJD. He outlined the components of effective exposure: sufficient dose, effective route of exposure and further

discussed the relevance of species barrier. Each of these was described in detail and with specific information regarding CJD. He reviewed particular limitations of animal experimentation, including the need for large numbers of experimental animals if the transmission rate is low and the important impact of the species barrier. He noted that while transgenic mice have exciting potential for studies in CJD, there may be variations in susceptibility to pathogenesis. He reviewed the existing animal evidence, concluding that if blood can lead to disease when injected intra-cerebrally, then there is potential for peripheral administration to lead to infection, if there is sufficient agent. Dr. Asher reminded the audience that most information regarding infectivity of human tissue is based on tissues harvested at autopsy, and that this information may not accurately infectivity of tissue taken during life. In addition, he cautioned that the spinal fluid test currently under examination will not be an effective screen for CJD since it had usefulness only in persons with clinical illness and since the test requires a lumbar puncture. It's prime usefulness is distinguishing between certain types of neurological illnesses, however, the number of people tested and the types of clinical situations in which it had been tested are still limited.


Dr. David Westaway, University of Toronto

Dr. Westaway provided information about the variety of TSEs (more commonly known as prion diseases) among different animals, including man. He described evidence for different prion "strains" or isolates based upon incubation times and patterns of neuropathology. He stressed that biochemical purification indicates that a molecule, if present within preparations of prion infectivity, is unlikely to be greater than 25 base-pairs in length. In contrast to this situation, many avenues of research Bly indicate that an aberrant form of a host-encoded protein, PrP, as a major and essential component of the aetological infectious agents (the prion). The normal form of this protein, cellular PrP (PrPC) is present in all mammals, including humans. Though the role of PrPC is not well understood, it is thought to be a precursor to the disease-associated form of PrP, variously known as PrPres, PrPSc and PrPCJD. Conversion of PrPc to PrPSc is thought to involve refolding, templated by PrPSc itself: consequently, it can be hypothesized that sporadic CJD could be due to (i) overproduction of PrPC, such that misfolded forms of PrPC akin to PrPSc accumulate, or (ii) somatic mutation in the PrP gene, such that mutant PrPCs are synthesized which fold into PrPSc-like forms. At this time all evidence indicates that there is only one locus for human familial prion diseases, namely the prion protein gene (PRNP), located on chromosome 20.

Dr. Robert Will, UK Surveillance

Dr. Will described the initiation of the UK surveillance in the 1990's in response to the recognition of the epidemic of BSE in the UK. He described the basic activities of the surveillance system, which consist of reviewing referrals, about half of which are not CJD. In recent years, increasing numbers of CJD reports have been received, but the excess was mainly among elderly patients, and the increase has occurred among all countries including those without BSE. He described certain features more common among those with iatrogenic CJD, noting that a distinctive clinical pattern can be recognized in many patients. However, he also said that these patterns do not have sufficient accuracy to deduce, in isolation, the cause of any one person's CJD.

Very recently, Dr. Will and his colleagues described a new variant of CJD (NV-CJD) with startling clinical and pathological characteristics. To date, 11 cases have been described in the UK and one in France. The predominant characteristics are the young age at diagnosis (median 27.6 yrs), long duration of illness (median 13 months) and remarkably consistent clinical presentation with psychiatric disease. In addition, dysesthesia predominated among the physical symptoms. The PrP load was high, as seen in image analysis and the features of plaques surrounded by spongiform change were characteristic. To date, no cases have been found among persons dying in earlier time periods and no cases have been found in countries free of BSE. He concluded that NV-CJD "remains an unexplained aggregation". Clearly, it is possible that TSE contaminated materials could have entered the human food chain in the form of BSE contaminated brain and spinal cord. Transmission studies are underway in the UK as are continued epidemiologic and surveillance investigations.


Dr. Andrea LeBlanc, Lady Davis Hospital

Dr. LeBlanc reviewed the mutations responsible for up to 10% of human TSE. The familial TSE include: CJD, Gerstmann-Strussler-Sheinker Syndrome (GSS), Fatal Familial Insomnia (FFI). The prion protein gene is located on chromosome 20 and known mutations are located within the coding region of the prion protein. The gene provides the information necessary for the transcription of the prion mRNA which transcribes the naturally occurring human prion protein. The function of the protein is unknown, although there is certain information available from experiments involving mice who lack the ability to produce normal prion protein. Scientists have observed diminished synaptic transmission in the brains of these mice. Dr. LeBlanc provided detailed information describing the current known insertion and substitution mutations leading to human disease. She briefly discussed the predictive value of particular mutations, including specific information on certain gene mutations which have high penetrance and those with low or uncertain penetrance. Dr. LeBlanc described variations in normal gene sequences which may be associated with susceptibility to iatrogenic CJD. Particular information regarding a shared mutation in FFI and CJD was provided, including intriguing finding that supplementary sites determine the phenotype. She briefly discussed the new theory of protein X as proposed by Prusiner et al. Dr. Prusiner has proposed that an as yet uncharacterized protein acts upon the abnormal and normal form of prion protein to convert the normal prion into the pathogenic form. The pathogenic form is responsible for the development of the clinical syndromes seen in prion encephalopathies.


Dr. Dessa Sadovnick, University of British Columbia

Dr. Sadovnick presented on the issues surrounding counseling and consent in investigations of familial, heritable diseases. She defined genetic counseling as "a communication of human problems which occur or risk occurring as the result of a genetic disorder". She noted that for single gene autosomal dominant heritable disorders with high degrees of penetrance that the family members are usually aware of their family history. She provided scenarios of predictive testing using family trees as a technique for reviewing the conflict between the "right to know" and the "right not to know" when family members are tested for genetic diseases. She reminded the audience of the difficulty of making predictions when the mutations and/or polymorphisms have low predictive values. She continued by differentiating predictive testing from risk assessment, where risk assessment is a broader concept wherein all risk factors which alter the risk of a disease are evaluated. She noted that persons with relatively rare disease often do not have the base levels of awareness which families with familial disease have of the particular disease. She cautioned that people vary in their ability to process information about genetic disease, mentioning self perception of "all or none" risk levels. Finally, she advised that consent and confidentiality must be assured regardless of the mutation or gene substitution identified.


Construction of Risk Assessment, chaired by Dr. Nobert Gilmore

The opening session of June 5 focused on the present state of scientific understanding about CJD. Because CJD is a relatively rare disease with a typically long latency period, and because of difficulties raised by cross-species study and other factors, definitive medical information is sparse. Uncertainty about the disease is certainly high, creating special public health problems. Overall, the preponderance of scientific evidence is that the likelihood of infection by blood or blood products lies somewhere between "theoretical" and extremely low. However, CJD is a horrible disease, resulting in serious deterioration of both neurological and motor functioning, and is commonly fatal within a few months of the onset of symptoms. Consequently, the June 6 sessions followed the theme of "Construction of Risk." Speakers explored the particular problems and issues arising from this "low risk - high consequence" disease.

Although Dr. Paul Slovic, of the University of Oregon, could not attend as scheduled, his colleague Dr. Gary McClelland presented his remarks titled, "Risk Perception, Media, and the Vulnerable Society: The Social Amplification of Risk from Mad Cow Disease." Slovic demonstrates certain similarities between the BSE "crisis" today and the infectious disease pandemics found throughout history. There are important differences as well. Notably, due to increasing technology, medical sophistication and monitoring of such catastrophes, they are much less likely to occur than in past. However, our ability to identify, publicize and take effective steps to address such problems at an early time itself has profound social, political, industrial and economic impacts. The BSE scare is an example of how the reduction of our vulnerability to pandemic comes at the cost of increasing our vulnerability to social and economic calamity in the face of a serious public health menace.

An understanding of the perception of risk is essential to the design of good communications strategies. The perception of risk by members of the public is systematically different than that of the technical expert, who sees risk as being comprised of just two elements - the probability that something will go wrong and the seriousness of the consequences if it does. Members of the public tend to focus on a range of other factors, including: whether the risk is voluntary or involuntary to the person exposed; whether and to what extent the individual can control the risk; whether there is an emotional component such that it seems a "dread risk"; whether the person exposed benefits from undertaking the risk; and whether adverse consequences are immediate or delayed.

The perception of risk can lead to stigmatization, not just of people or groups, but also of things, products, technologies and places. Blood faces such stigmatization as a result of its public perception as a hazardous product. The same may be said of beef products in the context of their feared role in the transmission of CJD. The risks posed by blood and beef are seen as uncontrollable by the individual and, it is feared, by the experts as well. Often, there are no practical substitutes for blood. In addition, contracting CJD is a dread risk - one perceived as having horrific and fatal consequences. Further, the risk is abnormal inasmuch as these products (blood and beef) are not normally considered to be inherently risky.

The level of trust in the person bringing a message of risk is very important. Accordingly, the current distrust of experts and authority creates a significant barrier to a realistic public perception of the risks associated with CJD. Also significant are the emotions inspired by the image of the risk. For example, nuclear power and cancer have Bly negative images. Therefore, communication strategies relating to blood should take account of the images in people's minds of giving and receiving blood. Helping people to understand risks and to put them into perspective is a difficult and multi-facetted, but very important task.

Dr. Robert J. Griffin, Director of the Center for Mass Media Research at Marquette University, spoke on "Communication and the Construction of Risk in Conditions of Uncertainty." Dr. Griffin analyzed issues around the construction of risk in the context of a study of the public response to an information campaign concerning two water quality problems faced by the City of Milwaukee. These were lead in tap water and an outbreak of cryptosporidiosis also from the water supply. More generally, his remarks addressed the way media reports might shape public perceptions of risk.

There are cognitive, emotional, and behavioural responses to risk, all shaped to some extent by the social construction of reality. Communications media, particularly mass media, are more likely to influence perceptions when their audience is either confused or lacks relevant personal experience about the risk in question. He suggested that, in their understanding of the risk of CJD, the public might tend to default to its experience of AIDS as the relevant framework. The mass media has no "magic bullet" affect on public perception. Advertising and information campaigns cannot ensure that attitudes will be shaped, and behaviours are even more difficult to change.

Generally, people are uncertain about a risk when: (1) they feel personally exposed to the risk (minorities, persons of lower social status and to some extent women tend to feel more exposed); (2) they have difficulty conceptualizing risk estimates; (3) they feel that neither they, nor a trusted agency, can control the risk; and (4) they do not trust the body that is supplying information about the risk. From the lead in tap water study, a number of tentative conclusions were drawn. First, a health risk media campaign is not always effective. It can contribute, to some extent, to short-term cognitive awareness, but is less successful with long-term emotional responses which may be tied to behavioural change. Mass media sources may effectively impart ideas and awareness of new behaviours. However, inducing preventive behaviours is more difficult, particularly for a disease that people do not have and are unlikely to get (where preventive behaviour would make an unlikely event less likely).

The study found support for the "knowledge gap" hypothesis, that better educated people tend to acquire risk information more readily than persons of lower education and status. Paradoxically, lower status persons often tend to be more at risk from a variety of hazards (as indicated by the waterborne lead study) and so their requirement for the information and behavioural change tends to be greater. Neither mass media nor government sources (specifically pamphlets) seemed to be very effective in encouraging preventive behaviors. Neither proved to be as effective as the intervention of an expert "change agent" such as a physician or other health professional, in a trusted interpersonal relationship. At bottom, different types of people require different approaches, types, and focuses of information.

Several questioners took the opportunity to explore these issues further. Generally, and in the particular case of CJD, Dr. Griffin stressed the importance of including interpersonal approaches in any program designed to encourage preventive behaviour. He also emphasized the importance of pre-testing of information sources to check responses. Views were also exchanged about public perceptions of the media and how it gathers information. This raised the question of trust and whether people differentiate between the medium in which information is presented and its original source. One questioner was interested in both the protective and destructive potential of fear. In this regard, what constitutes responsible media behaviour? Finally, there was a brief discussion of the mode of information presentation, recognizing that some in need of information about risk will not be functionally literate, or English speakers, or people who typically take notice of written materials. A more graphic presentation of information tends to stay in memory more effectively, but reaching all affected persons remains an acute problem.

Dr. Gary McClelland, of the University of Colorado at Boulder, Department of Psychology, returned to present his own remarks titled, "Psychology of Risks Related to Creutzfeldt-Jakob Disease." While little direct research has been done on the psychology of risk of CJD, illumination may be gained by analogy to other low probability, high consequence events. The first striking conclusion is that individual differences in risk judgement are substantial, tending to a bimodal distribution. An example offered was that of a housing development built on a rehabilitated California landfill. When the probability of harm is low, people tend to either overcompensate for the risk, or discount it pretty much altogether. A study of persons faced with the small possibility of having radon gas in their homes exhibited a similar split. Faced with the choice of purchasing a radon gas test kit, and acting on the information gained from the kit, researchers found that those in lower risk areas, which tended to be higher income neighbourhoods, were more likely to purchase kits and take rehabilitative action. Those in the target area, being at greater risk of having radon gas, bought relatively few kits. His conclusion was that almost no one will "get it right" - people are either too concerned or not concerned enough about particular low-probability, high consequence risks. Further, if warned, most who take action tend not to need to and those who do not take action probably should. Effective risk communication depends very much on the individual and targeting those most in need of managing or controlling a risk is very difficult.

Dr. McClelland noted also that risk raises the possibility of two types of errors. People may be alerted of a risk that does not occur (a false alarm) or people may fail to be alerted to a risk that does occur (a miss). Excessive concern about false alarm drives indecision - people may be frozen by too much worry about an unlikely event. But worries about a miss may cause excessive warning. Either can have harmful or disastrous consequences. Recognizing both types of errors reinforces the need to balance the likelihood of error in developing strategies for informing persons about risk.

Dr. David Paltiel,of the Yale School of Epidemiology and Public Health and the Yale School of Management, then spoke on "CJD: Insights from Simple Models." His thesis was that notwithstanding substantial uncertainty, decision-making about risks can be assisted by modelling techniques. CJD invites a number of possible public health responses and decisions. Among these are blood product recalls, the development of donor exclusion

criteria, recipient notification and others. Despite legal, ethical and economic uncertainties and the constraints of time and money, decisions must be made. Clearly, doing nothing also represents a decision which should be thoughtfully considered. Dr. Paltiel suggests that models can promote a more reasoned decision process. In short, quantitative analysis can bolster qualitative insight.

Three "dangerous ideas" are proposed. The first is that if a public policy intervention saves even one life, it is worth it. To demonstrate the dangerousness of this idea, the real-life example of mandatory prenuptial HIV screening in Illinois was discussed. This program was introduced without regard to expense, on the basis that the infections averted would be worth (almost) any cost. Dr. Paltiel demonstrated, by analyzing the number of tests and the prevalence of HIV infection together with certain conservative assumptions about the sensitivity, specificity and cost of HIV tests, including the likelihood of false positive results, that the cost of averting infection by this initiative is extraordinarily high. The money could be used in other ways more to prevent a greater number of infections.

The second dangerous idea is that the blood supply is inviolable and that only a 100% guarantee of safety is acceptable. However, so long as human blood is used, some element of risk is unavoidable. In the context of CJD (or any risk) again, two types of errors are possible. First, blood may be declared safe when it is not. This is the big mistake which we all fear, which creates a risk of transmission and which violates public trust in the integrity of the blood supply. Second, safe blood may be incorrectly identified as unsafe. This mistake carries costs as well. The blood supply may be depleted, recipients may have to wait longer for blood products, tissue acquisition costs may rise and anxiety and fear may be needlessly created. The idea that the blood supply must be guaranteed safe ignores the potentially fatal consequences of this second type of error. Again, balancing these risks of error facilitates sensible decision-making. Quantitative models are helpful in this regard.

In the case of the risk of transmission of CJD, having reliable information about incidence and incubation period, and making certain conservative estimates of the likelihood of transmission, the risk of transmission of CJD appears to be within the range of acceptable risk associated with transmission of HIV. Focusing exclusively on the harms which arise from failing to warn of unsafe blood may cause us to ignore the very real harms caused by alerting the public about blood which is in fact adequately safe.

The third dangerous idea is that analysis is useless because nobody can predict what will happen in the future. Indeed, it is neither intended nor necessary that modelling predict the future. Such quantitative analysis may yield qualitative insight in a number of ways: by making assumptions explicit; by imposing discipline and structure upon the process of decision-making; by illuminating features essential to decision-making; and by identifying research needs. In addition, modelling can act as a proxy for experimentation and program evaluation and foster discussion and highlight differences among stakeholders.

The question session featured challenges to Dr. Paltiel on his modelling of the risk of CJD transmission in a couple of areas. First, his assumptions about prevalence and transmissibility do not take account of the fact that patients often receive many units of blood products and that, because of the pooling of donated blood, a single recipient is exposed to the donations of a great many individuals. Second, the model must be made more sensitive to other sources of uncertainty inherent in the process. As examples, the model should account for difficulties in inactivating instruments and equipment, relevant differences in the production of different types of blood products and the effect of dilution in the pooling process.

Mr. Oliver Morton, Editor of Wired Magazine and former Science Editor of the Economist, closed the afternoon session with a free-wheeling talk on the media. The theme of his remarks was how the media generally, and journalists in particular, attempt to bridge between democracy - the voice and will of the people, and expertise - the facts, or voice of the natural world. His case in point was the recent debate in the U.K. about CJD and Mad Cow Disease (BSE), noting that all types of topics, relating both to people (democracy) and to nature, were intermixed in the media handling of this "crisis." BSE/CJD stories had a number of contexts, including those of emerging diseases, pesticides and organic farming, food scares, factory farms, distrust of government, Euroscepticism and the live export of animals.

In 1986, BSE was presented as a scientific oddity, little more. However, in 1988, it flowered as a crisis with its possible link to CJD. BSE was made a notifiable disease. The images of BSE were exemplified graphically by quite famous pictures of staggering cows, burning cows and a high-ranking member of the government feeding a hamburger to his young daughter. The media soon lost interest and between 1989 and 1995, there was no sustained coverage of the story. Isolated pieces appeared, driven either by events - science and agricultural journalists doing reports on the science, epidemiology or regulation of BSE or by investigative reports about particular cases of CJD, the horrors of abattoirs or the views of scientific dissidents. In late 1995 came the report of the abnormal or variant cases of CJD. The story approached crisis treatment, but then quickly vanished.

On March 20, 1996, the UK health minister released evidence of new variant CJD cases, raising an outcry of shock, distress and blame. Quickly, the focus of the media discussion moved to the response of the farmers, the European authorities and McDonalds restaurants. The government, worried about an overreaction, backtracked and partially reversed its position. At this point, the perception of the perception of risk was driving much government policy. In time, when the Europeans refused to lift the ban of British beef, the highlight of the story shifted to the resulting fight with the Europeans. Accordingly, the transition was complete when this health/agricultural story ultimately resolved itself into a typically political story.

In retrospect, the attention of the media brought mixed results. While public awareness was raised, the perception of the risks posed varied greatly. Information was made broadly available, but so was much disinformation. Finally, the government responded, but in a way which was not clearly satisfactory. The public was not reassured and the government remains at odds with the Europeans over the issue.

In discussion, Mr. Morton was asked why he felt the public debate developed as it did. In response, four important elements of the crisis were noted. First, the debate was both poorly understood (since very technical) and concerned a very nasty disease. Second, the epidemic was or is pretty much isolated to the U.K. and the window of risk had been closed with the 1989 regulations. Third, the media is highly competitive - driven by speed and sensation, very political - both internally and externally and tends to be poor at capturing and communicating technical expertise. Finally, the handling of the crisis was very much a product of the way that the government works and its political imperatives of cover up and spin management.

When asked how the media coverage of the issue could have been improved, Mr. Morton's suggestions included better science reporting including better use of in-media science expertise, a government which takes seriously the task of informing the people and a journalistic ethic that values providing information that can be trusted, and which is not driven by the biases and interests of individual media sources.


Ethics, Law and Policy Session, Chaired by Dr. Margaret Somerville

Dr. Somerville opened the session by noting that good facts are essential for good ethics which in turn is required for good law. Consistent with this notion, many of the speakers in this session had amended or rewritten their presentations as a result of the information presented during the scientific session the previous day.

Dr. John Last, University of Ottawa

Dr. Last was one such person and began by noting that he had amended his presentation following the scientific session. Dr. Last made the following observations about his approach to the ethical issues surrounding public health and CJD: Recounting the story of a Greek philosopher who was hit on the head by a turtle dropped from the beak of a passing bird, Dr. Last raised two questions. First, is the risk of transmission of CJD greater than the risk of being hit on the head by a turtle? The fact the latter occured proved the risk was greater than zero. Precaution against the risk must therefore be considered and if the risk is significantly greater than zero, precautions should be implemented. The same is true of BSE/CJD. The problem, however, is that we don't know what precautions would work. Secondly, therefore, what should be the appropriate public health response in light of this risk?

In considering these questions, Dr. Last used as his starting point the recommendations of Sheila Gore published in the British Medical Journal in March 1996 (Vol. 312 at p.791) when the problem of BSE and CJD arose in Britain. The recommendations had as their basis a comparison with HIV and contained key actions which aimed to safeguard public health in the context of BSE and CJD. The issue for consideration was which, if any, of these recommendations should be implemented in Canada.

In response to questions from the audience during the discussion which followed his presentation, Dr. Last stated that he thought that the most useful of the recommendations would be those advocating collaboration on core data acquisition. There is no evidence that recommendations such as the exclusion from blood, tissue and breast milk donation of children of a parent with CJD would be a useful public health measure.

Another important issue is how do we communicate with the general public, and what do we say? Do we have enough facts to do this? Should we embargo beef? In Dr. Last's opinion, these questions are rhetorical in Canada at the moment because there is not enough evidence yet to justify these actions. For example, there has only been one case of BSE in Canada - in a domestic cow imported from the UK and a few cases of Chronic Wasting Disease in farmed elk. Dr. Last concluded that the BSE experience in Britain indicated that it can be dangerous for humans to interfere in the natural order of things, for example by feeding animal protein to herbivores such as cows (as was done in Britain until banned in 1989).

Dr. Last noted the need for case control studies. Although CJD is a rare disease, it is nevertheless possible to undertake case control studies with very small numbers. Dr. Will informed the meeting that a case control study has been under way in the UK since 1990, and from 1993-1995 the UK was involved in a collaborative study with several European countries. Information has been obtained on 440 cases, and the results are currently being prepared for publication. Problems were faced in the studies in trying to obtain information on past dietary exposure, especially because of recall bias. People being studied are not in a neutral state with respect to the questions they are being asked, but know why the researchers are seeking certain information and the substance of the response that would be scientifically relevant.


Discussion

Following Dr. Last's presentation, the issue of disclosure of information to the public was discussed. A plaintiff's lawyer involved in HIV litigation in Canada noted that there was an obligation of full disclosure about the risks of transmission of CJD through the blood supply. Dr. Last agreed that full disclosure was necessary, and stated that we should admit ignorance when we are ignorant. However, the evidence at the moment is such that we should not be making alarmist statements or implementing exclusionary practices.

Dr. Somerville highlighted two issues raised by Dr. Last in the form of two questions:

  • 1. Should the normal presumption (that we are free to act, and conduct should not be prohibited until unreasonable risks or harm arise) be reversed for non-natural events? In this case, feeding animal protein to herbivores would need to be shown to be reasonably safe before it was done.
  • 2. What do we do in terms of disclosure of risks of which there is very little evidence, particularly in light of the decision of the Supreme Court of Canada (Hollis v Dow Corning) in which it was held that risks need to be disclosed even where not yet confirmed.


    Dr. David Rothman, Columbia University, New York

    Dr. Rothman noted that he too had rewritten his paper as a consequence of the data presented at the scientific session the day before. He had not anticipated the weakness of the data with respect to the real threat to the blood supply.

    He described the response of the United States federal government to the threat of hepatitis B in the blood supply in the 1970s. In remarkable contrast to the approach we have now to the threat of CJD, the threat of Hepatitis B was met with complacency and little anxiety. In the 1970s, everyone knew that the blood supply was contaminated and that transmission rates of infection were quite high. There were known rates of mortality and morbidity - 100,000 post-transfusion hepatitis cases and 850 deaths per annum. The known rates prompted efforts to formulate blood policy in the US, the main message of which was that if you adopted a volunteer blood supply, then the levels of risk would decline.

    This was the main argument of Titmus in his book The Gift Relationship, which examined US blood policy in the 1970s. Titmus believed that the blood supply in the US was unsafe (in comparison to the UK) because the blood was sold and not donated. Titmus' latent arguments were that altruism is superior, as a governing principle, to the market place, and that government regulation was to be preferred to the autonomy of the market place. In response, the Chicago Law and Economics School argued that the blood safety problem was due to the selection of people who were giving blood, not due to blood being bought and sold. Attacking the market place, as Titmus had done, was unfair because the government had intervened and corrupted the market place by enacting legislation which removed manufacturer's liability for the defective blood. This led to problems with the safety of the blood supply.

    The US government policy and reaction to the problem of Hepatitis B transmission was inadequate because:

    This lack of response on the part of the US government to the risks and harms inherent in the blood system was a reflection of the idea that the quantity of the blood supply must be maintained. This was the primary consideration and dominated all thinking. For example, the 1972 US blood policy listed four elements to be taken into account: (1) supply; (2) quality (in terms of use in patients, not safety of the blood supply itself); (3) accessibility; and (4) efficiency. The issue of safety of the blood supply itself is not discussed until page two of the policy.

    Hepatitis was not considered a concern, despite the known mortality rates from post-transfusion hepatitis, and there was no fear of the possibility of unknown pathogens. In addition, these matters were regarded as being ones for experts, and there was therefore no need to discuss them with the public.

    AIDS turned the world upside down in terms of blood policy, and led to bitter complaints by the public: Why did the medical profession and other institutions not act on known risks? And why did they not tell the public?

    Consequently, there is now an absence of public trust in the government, blood agencies and the medical profession. The obligation of informed consent means that there is no choice but to disclose all material information. Of course this will produce great anxiety in the public but this can no longer be used as an excuse for non-disclosure. The problem in the CJD context is the very flimsy facts concerning the risk of transmission. The situation is not therefore analogous to HIV.

    Dr. Somerville concluded by saying that we need to identify our basic presumption: Do we see the government as interfering with the market place or as having the primary obligation to ensure safety in situations such as the regulation of blood safety? Who should have the primary responsibility? Is there a presumption of giving information as it becomes known or of withholding it until certain conditions are fulfilled?


    Dr. Nuala Kenny, Dalhousie University, Nova Scotia

    In considering public policy in the context of CJD, Dr. Kenny's main argument was that the matter is not one of information disclosure but of communication. Her presentation centred around four points: In Dr. Kenny's view the principled approach of autonomy, non-maleficence, beneficence and justice does not help us in determining how to respond to the public health issues surrounding CJD. For example, there may be a conflict between the principles of autonomy and beneficence, and the principled approach gives no indication of how to resolve such a conflict. Some of the alternatives to the principled approach which may be more useful are: Dr. Kenny concluded by emphasising that notions of trust, duty, and relationship are all essential to keeping the risk in perspective. The importance of scientific knowledge is not the only value to take into account. In her view, fundamental metaphysical and epistemological concerns are at the core of the essential question: How do we convey, in real, honest communication information about the risk of CJD?

    Discussion

    After Dr. Kenny's presentation there was some brief discussion about resource allocation. A public health practitioner from British Columbia noted that it cost $8 million to carry out a hepatitis C lookback, and there is a problem when this type of action is undertaken for liability reasons when the money could be spent, for example, on prevention programs for HIV or hepatitis B.

    In summary, Dr. Somerville noted that there was a challenge in relation to full disclosure, in terms of which risks and harms we chose to be vigilant about and what information we must disclose. The questions that Dr. Kenny brought up are wider than CJD

    - in particular the questions of trust and how we maintain it; what value system should be used to provide the framework of the debate; and how do we get beyond the impasse of autonomy vs do no harm. Dr. Kenny finally reiterated that information is essential for good decision-making but providing straightforward facts is not the only part of conveying of information. The role of the media is also important since most people get information from the media.


    Dr. Bernard Dickens, University of Toronto, Toronto

    Dr. Dickens focused on the risk of litigation to health professionals and institutions. He briefly outlined the difference between the US and Canadian systems. In Canada, the loser is liable to pay the legal costs of the winning party, and there is no right to a jury as there is in the US. In addition, in Ontario there is no contingency fee system as there is in the USA and in other Canadian provinces (although the other provinces also have costs sanctions). The risks of litigation for plaintiffs are consequently less in the US than they are in Canada. He outlined some of the bases upon which litigation against health care professionals and institutions is founded, that is, contract, negligence and fiduciary duty (which is being increasingly explored as a basis of liability by the courts in Canada and also in the UK).

    In the context of blood, products liability (that is, liability for a defective product) generally applies only if for example blood cells are used to make a product. It would not apply in the context of blood itself, since naturally occurring materials of the body are not considered at law to be "products". The principles of strict liability for products liability in the US do not apply in Canada which has a fault-based system of liability. Blood is considered at law to be inherently unsafe but not unreasonably dangerous, and therefore there is no automatic liability for any harms that result from its use.

    Dr. Dickens outlined the principles of criminal negligence, which is a higher order of negligence than negligence at civil law. The courts have generally not dealt with medical matters concerning negligence within the criminal law, although in the United Kingdom an anaesthetist was recently held criminally responsible for manslaughter. One difficulty with the criminal law is that for liability to attach for an act causing death. The death must occur within a year and a day of the alleged negligent act which caused the death. In the case of CJD, this would be unlikely because of the long incubation period of the disease.

    Liability for medical acts would, however, most likely be in negligence at civil law. A legal duty of care exists between doctors and patients, and has recently been held to exist between blood banks and recipients of blood (in the case of Pittman Estate v Bain). There may be problems in finding liability in negligence on the part of an institution such as a hospital, because of its organizational structure. There may also be a break in the chain of causation. For example if information is given to an intermediary, the learned intermediary rule may apply. This means that the caused link that gives rise to responsibility and liability between the blood agency or hospital and the ultimate recipient of blood is broken.

    Liability in negligence arises if the following elements are proven: (1) the existence of a legal duty of care (2) breach of the reasonable standard of care (3) damage consequent on that breach and (4) that the breach caused the damage. The standard of care, though measured according to what is required by the profession, is ultimately a matter of law. Thus, a practice consistent with standard professional practice may nevertheless be considered unreasonable and in breach of standard by the courts.

    The duty to take care includes a duty to disclose information about a medical treatment or procedure and its risks. This duty in turn includes assisting patients in interpreting the significance of the information disclosed to them. If the patient is not informed of a material risk, the health care professional can be liable in negligence. Adequately informed patients are allowed by the law to make bad choices, as a consequence of the right to autonomy and self-determination. In order to be successful in an action for negligence, the patient would also have to prove causation - that he or she would not have undergone the procedure if he or she had been told information about that procedure, including its risks, that the physician was legally required to disclose.

    There is also a duty to follow up and give information after an event that causes harm. Even if nothing can be done to treat or prevent a disease that may be contracted from a blood transfusion, the patient must be told of the risk, because it may have important consequences. Failure to give information after the event may deny people the opportunity to make future arrangements and to protect others. The information may also have important consequences in relation to employment and insurance.

    In order to meet the standard of care required at law in respect of information disclosure, health care professionals must keep abreast of information including the nature and probabilities of risks. In the context of CJD, health care professionals would need to keep up-to-date not only with facts concerning sporadic, iatrogenic and familial CJD, but also with developments regarding the new variant of CJD, and information on whether CJD is transmissible by blood. Information about CJD needs to be woven into clinical practice. For example, if a woman with familial CJD terminated a pregnancy and the fetal tissue was considered for use in treatment of Parkinson's disease, the transplant might be contraindicated because the tissues are more suspect than others. If such tissue was inadvertently used, transplant recipients might need to be informed.

    The extent to which hospitals have a duty to protect staff from harm depends on the risk of exposure. There is a problem in the context of CJD with the reuse of disposable medical equipment, problems of sterilisation and operator error, treatment that may not kill the infectious agent, and solvents that may cause damage to the equipment.

    Encompassed within the fiduciary duty of health care professionals is a duty to use information in the patient's best interests. How patients are told matters - communication, counselling and timing of disclosure of information - may impact upon the issue of the proper fulfillment of the fiduciary duty.


    Dr. Wendy Mariner, Boston University, Boston, Massachusetts

    Dr. Mariner focused on principles which guide responses to public health risks. Public health has values but may not have principles. But the law is about principles, and consequently sometimes there is difficulty in accommodating the interactions between law and public health. She noted that we don't have a formula in public health, public policy or law for dealing with issues of uncertainty and risk. In terms of the role of law, the issue becomes whether to regulate or not, and this depends on what constitutes the goal of regulation. Is the goal in these circumstances to prevent all future cases of the new variant of CJD or any future transmission of CJD to prevent human suffering? Or is the goal to preserve the market for British beef?

    If we can agree on a goal, it is then necessary to decide how to achieve it. The law does not tell us much about the means by which goals can be achieved - it simply sets standards. In the area of public health, the law has deferred to the public health expert to define the goals, and to recommend the steps to be taken to achieve these goals and remedy the problem. Public health wields a great deal of power with respect to the law's response with regard to what it will classify as either legally acceptable risks or legally unacceptable ones. One problem is that public health has never fully articulated what it means to classify a risk as "acceptable" or "unacceptable". Accordingly, there is no consensus over what amounts to an acceptable risk. In addition, public health responses are vulnerable to changing governments, who are often influenced by political lobbying.

    Dr. Mariner outlined three categories of risk:

    Public health does not tell us how to characterise risks into these categories, or who should do it. Thus, government risk regulation is sometimes perceived as unprincipled. So far, we have not succeeded in formulating a coherent set of principles to explain why we regulate, what we regulate, and how we regulate.

    Where public health authorities speak of all risks in the same way (as simply had), how is the public to distinguish one risk from another? The absence of credible distinctions can lead to two quite different problems. The first is public apathy or distrust. If government says that everything is bad for you without providing any guidance as to which is better or worse, people may cease to take major threats seriously. The second is public refusal to accept any risk at all. If all health threats are equally bad, people may not be willing to endure even negligible risks.

    It is therefore important to develop guiding principles for public health, particularly since the courts use principles as precedent to define what can and cannot be done. It is also important to consider both the ends and the means by which these ends are achieved. There is a difference between regulating things and regulating people, because people have personal rights that things do not have. People cannot be regulated as tightly as products and facilities. Things can be eliminated; people cannot. Where cows fit in this classification remains a matter of some ethical controversy.


    Dr. Myron Echenberg, McGill University, Montreal

    Dr. Echenberg discussed the history of the public health response to bubonic plague. He cited some case studies of the response in different cities around the world to illustrate some of the consequences and implications of those responses for public health policy. He ultimately concluded from this examination that there was not a great deal of international communication or collaboration between the different places. Consequently, the responses to the plague were varied and inconsistent. In some places, less than adequate responses lead to a discrediting of public health and a bad reputation for Western medicine in non-Western countries. It is important therefore to have disclosure and honesty in international exchanges.


    Risk Management (Responding to CJD) Session, Chaired by Dr. Maurice McGregor

    Health Canada, Dr. Maura Ricketts, Blood-borne Pathogens Division, Bureau of Infectious Diseases, LCDC

    Dr. Doug Kennedy, Bureau of Biologics and Radiopharmaceuticals, Drugs Directorate

    Dr. Ricketts reviewed the epidemiology of CJD in Canada, with reference to the possibility of transmission via blood and blood products. She noted that the risk of blood-borne transmission is theoretical, and that there is no evidence thus far that CJD can be transmitted from human to human via the peripheral blood route. She further noted that animal models have indicated this is possible, and at Health Canada is developing several initiatives (including a case-control study) to look for epidemiological evidence of such transmission.

    Dr. Kennedy outlined the Health Canada position on blood and CJD transmission, and provided information on the regulatory role in the possible transmission of CJD via blood and blood products.


    Canadian Red Cross Dr. M.T. Aye, Canadian Red Cross

    Dr. Aye reviewed North American blood and blood product recalls and withdrawals, and provided information on the cost of such actions and the consequent supply shortages. He briefly referred to the impact of shortages.


    Alberta Experience Dr. John Dossetor, University of Alberta

    Dr. Dossetor gave a presentation on the process of decision making around recipient notification in Alberta. Dr. Dossetor reviewed the major ethical issues that had to be considered in deciding the course of action: public trust, prevention of harm, and the public's right to know. He also spoke about the principles at stake in these situations: mutual dependence, autonomy, non maleficence and beneficence.


    Risk, Panic, Public Debate and the Role of the Citizen Dr. John Ralston Saul, Toronto

    This presentation provided an overview of the issues brought up in these sessions. Dr. Ralston Saul spoke about individual and collective or societal concerns, and also the difficulty that the medical community faces in balancing the "right to know" with the "right to not know".

    The afternoon concluded with an open forum for the discussion of these items. HC-SC Last modified December 3, 1996


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