Do we have an ethic of causal cognition in assessing post-vaccination harms?

1. Do we have an ethic of causal cognition in assessing post-vaccination harms? 中正大學因果關係工作坊, Sep. 10, 2010 Kevin Chien-Chang Wu 吳建昌 Department of Social Medicine, National Taiwan University College of Medicine Department of Psychiatry, National Taiwan University Hospital E-mail: ccwu88@ntu.edu.tw

2. Outlines • Introduction: From SARS to H1N1 flu • The importance of vaccine development and inoculation • The conundrum of post-vaccination harm • From negligence liability to no-fault liability • Taiwan’s post-vaccination harm relief institution • American legal literature on scientific evidence • Daubert、Joiner、Kumho Tire • Randomized controlled trials • The hierarchy of scientific evidence in the discourse of evidence-based medicine • Plural theories of causation in legal policy choices • The limitation of statistical evidence • Nancy Cartwright: Metaphysics, methodology, and application of causal theories should be considered together • Pragmatism and humility in causal cognition in legal policy making • Review process of the post-vaccination harm relief application • Public participation and transparency • Temporary conclusion

3. “I am sure that what any of us do, we will be criticized either for doing too much or for doing too little… If an epidemic does not occur, we will be glad. If it does, then I hope we can say… that we have done everything and made every preparation possible to do the best job within the limits of available scientific knowledge and administrative procedure.” （US Surgeon General Leroy Burney, Meeting of the Association of State and Territorial Health Officers, August 28, 1957）

4. From SARS to H1N1 flu • In 2003, the epidemic of SARS in Taiwan actually was an unprecedented auditing on Taiwan government’s capability of risk governance and public health management. Even though Taiwan barely passed the auditing, many people are still haunted by the feelings of around that time • Emerging infectious diseases with new spread patterns: • Globalization (Economic, etc.) • Rapid transportation • Preparedness is the priority: • In the post-SARS era, how to swiftly develop vaccines for large scale inoculation is a very important public health measure.

5. The dramatic development of H1N1 flu epidemic and vaccination • In 2009, H1N1 epidemic developed after its so-called first outbreak in Mexico. • In Taiwan, news reports focused on how many persons were quarantined, treated, and whether Taiwan could stop the epidemic at its borders. • However, as group infections were reported more and more, the news focus shifted to the development and the strategies to initiate large scale vaccine inoculation. • As more and more people received vaccine inoculation, more and more cases of suspected vaccination injury were reported and people’s willingness to receive vaccination diminished. • The conundrum and dilemma on determining causal relation between vaccination and harm

6. Kinds of legal liabilities in civil law • Intention • Negligence • Gross • Concrete slight negligence • Abstract slight negligence：reasonable and prudent person • Quasi no-fault liability • Avoidability • Equity (financial consideration) • Partial or full responsibility of the those who have no mental capacity or diminished capacity during tort behavior and his or her legal representative has no fault in monitoring the tortfeasor’s behavior (Taiwan Civil Act Sec.187) • While employees are the tortfeasors, even though the employers have fulfilled their duties of monitoring, the employers have to take partial or full responsibility • Risk • General：prima facie assumption of causation and negligent liability • Specific: prima facie assumption of causation and no-fault liability • Limits of the technology feasibility • The most strict • Where there is harm there is liability

7. The evolution of tort law and liability patterns （1/2） • Conflicting functions of tort law • Declaring moral blame （retributive justice） • Compensation the victims（corrective justice） • Deterrence of in appropriate behavior • General deterrence, specific deterrence • Distribution of the costs of harms by attributions of harms（Distributive justice） • The theoretical foundations of negligent responsibility • Morality: individual autonomous rational choices • Harmonization of individual freedom and social safety: the evolution of tort law is intimately related to social economic activities and technology risks • Attribution of responsibilities is a demonstration of respect for autonomy • Initial evolution • The objectification of standard of care: the deletion of the consideration of individual morality • Shifting the burden of proof from the plaintiff to the defendant (equity concerns about legal weapons in litigation procedure; protecting the vulnerable and weak plaintiff)

8. The evolution of tort law and liability patterns （2/2） • From negligent liability to risk liability (accountability) • The institution of negligent responsibility could not meet the goal of protecting social safety • The tortfeasors produce and control the sources of risk • Tortfeasors benefit from their risky behaviors • The tortfeasors could spread the risks through market price and insurance • Through the adjustment of the range and degree of responsibilities, the enterprises could predict their business risks such that they would not withdraw from the market due to cost concerns • The future of tort law: combined considerations of justice and efficiency

9. Taiwan Regulation on Vaccination Injury Relief Fund and Review（1/2） • In 1986, polio vaccination injuries appeared in Taiwan • In 1988, Taiwan began to implement vaccination injury compensation schemes • After several revisions, the newest revised regulation was implemented on Feb. 12, 2010. (After the outbreak of H1N1 flu and many reports of post-vaccination harm) • Sec. 2 of the regulation, those who were harmed due to vaccination could seek relief according to the regulation • Remedy is not liability • “Strict” liability: no fault need to be found for the relief

10. Taiwan Regulation on Vaccination Injury Relief Fund and Review(2/2) • Sec. 2-1: the manufacturers or import enterprises must donate a certain amount of money for setting up the vaccination injury relief fund: one NT dollar for each potential inoculation • Sec. 4: there shall be 19-25 members in the review committee; the committee members shall be appointed by the central competent authority from the pool of experts in medicine, health, anatomy and pathology, law or neutral and objective persons in society. The proportion of legal experts and neutral and objective persons in society shall not be less than one third of the whole review committee. • Sec. 4-1: When deemed necessary, the review committee could designate a member or entrust competent agencies, academic institutes to conduct preliminary inquires and research; If necessary, the review committee could invite competent agencies, scholars or experts to participate in the authentication or attend the review committee meetings for counseling. • However, it does not reveal the principle in reviewing the factual causal relationship between vaccination and harm • Section 7: if vaccination could not be ruled out as the cause of the harm, the amount of relief would be lower than that with vaccination as the definite cause

11. The development of the Vaccine Injury Compensation Programin the U.S. • In 1960s and 1970s, there were many case reports on injuries related to DPT (diphtheria, pertussis and tetanus) vaccination and polio vaccination. Many ‘victims’ or their legal representatives sued through tort law courts. • Facing the insurmountable spending on litigation cost, time and labor, and large amount of awarded damages, vaccine companies withdrew from the market gradually. • The U.S. government worried that the lack of enough supply of vaccines might induce tremendous public health hazards: lack of vaccines to prevent those preventable infectious diseases, therefore the U.S. Congress in 1986 promulgated the National Childhood Vaccine Injury Act（NCVIA) in order to maintain the supply of vaccines through a no-fault liability system coupled with damage caps. • In 1988, following the act, the U.S. initiated the Vaccine Injury Compensation Program（VICP）

12. The compensation patterns in VICP • The injury in a child must last more than 6 months, and death or severe harm that warranted in-patient treatment must be present. • First, Table claims • The VICP will compensate according to the table of vaccines and their related serious vaccine injuries. • The petitioners only have to prove that their conditions are among what are listed in the table. • Second, causation in fact claims • If the petitioners’ conditions do not match the table listings, they could maintain that under the rule of preponderance of evidence, there is factual causal relationship between vaccination and injury • However, even in a no-fault liability system, how to prove the existence of causation is still a huge challenge to the petitioners

13. The realities about VICP • Empirical studies have shown that, after several adjustments of the compensation table by the Department of Health and Human Services (HHS), the proportion of table claims actually diminished these years. Many petitioners had to seek compensation by the cause-in-fact claims. • However, in an adversarial legal procedure, the legal representatives of the defendant, HHS, actually fought to the end for winning the litigation, and the reality was: (1) many cases lingered for long time in the legal procedure, (2) there was no consistent criteria for assessing the causal relationship between vaccination and injuries, (3) many petitioners actually did not get speedier compensation in the new system. • Recently, in the U.S. there have been petitions on the alleged harm, autism caused by MMR (measles, mumps, rubella) vaccination and the inoculation of other vaccines that contain thimerosal. In recent three index petitions, three special masters hearing the cases found against the petitioners and emphasized on the lack of scientific evidence for the claims of the petitioners. Many scholars praised the decisions and said this could alleviate the improper panicky fear about vaccination and contribute to maintaining the public’s health. • What could we learn from this about the H1N1 flu pandemic vaccination compensation policy?

14. Factual causation • As the research on pharmaceutical or toxin injuries increased, legal courts became more and more dependent on scientific statistical evidence • A common confusion: merging the concept of statistical probability（ex. Probability of injury is more than 50%）and that of preponderance of evidence (the persuasion power of the evidence is more than 50%） • Usually scientific statistical figures are “fact probability”, but preponderance of evidence is a “belief probability” • The potential problem: legal courts cherish scientific statistical figures and disregard the need for other evidence that might also have referential value in determining causation

15. RCT and EBM • Randomized controlled trials (RCT） • Randomized assignment of research subjects into control groups (receiving placebos) and experimental groups (receiving experimental drugs) • “Double blind” to delete the influence of knowledge and expectation • Control group as the counterfactual for the experiment group; if there is significant statistical difference between the therapeutic effects of the control and experimental groups then it means the experimental drugs are effective. • The US Food and Drug Administration has taken RCT as the golden standard • Evidence-based medicine (EBM） • Emphasis on the physicians counting on best scientific evidence, no unreliable clinical experiences • Hierarchy of the reliability of scientific evidence basic clinical epidemiology: meta-analysis of the RCTs is the best evidence; individual clinical experience is one of the lowest quality of evidence

16. Increased emphasis on scientific statistical evidence in the U.S. legal courts • Frye v. United States（1923） • The production or research on the presented scientific evidence must be generally accepted by the scholars or practitioners in the field. • Daubert v. Merrel Dow Pharmaceuticals（1993） • (1)scientifc evidence must be testable • (2)scientific measures must have error rate • (3)scientific evidence must be peer reviewed • (4) The production or research on the presented scientific evidence must be generally accepted • General Electric v. Joiner (1997) • If no abuse of discretion, the judges could use the above factors for considerations flexibly. • Kumho Tire Company, Ltd v. Carmichael et al. (1999) • Even when it comes to expert evidence, the above considerations also apply • The new rulings implied that the U.S. Federal Supreme Court will look to quantitative evidence for deciding on factual causation issues. • Empirical studies have shown that if the defendants could not present the well-designed quantitative studies to demonstrate the causal relationship in pharmaceutical injuries cases, most of the time the defendants did not have a day in the litigation.

17. The limitations on RCT • Many RCTs have their own quality problems • Many subjects who participated in research were very different in characteristics from those of the real world patients; there is external validity problem • Selection of a group of subjects on whom the experimental drugs tend to be effective • The numbers about the effectiveness of the experimental drugs actually are the averages; we could not rule out the possibility that a minor B subgroup might actually be harmed by the experimental drugs, but after averaging, the results might still be that as a whole the experimental drugs are beneficialfor all the subjects in the experimental group

18. Plurality of causality1 • Austin Bradford Hill (1965) • Strength of association • Consistency of association • Specificity of association • Temporality of events • Biological gradient in dose-responses • Biological plausibility • Consistency with the known facts • Proved by experiments

19. Plurality of causality 2 • Nancy Cartwright (2007) • Actually we have plural theories of causation in philosophy and daily lives; that is, causation has plural meanings • Plurality of causality is revealed in: • Metaphysical foundations • Methodology and judgment • Practical application • “Metaphysics and method should march hand in hand. If we have an account of what causation is then we ought be able to explain why our methods for licensing causal claims are good methods for finding just the thing we say causality is.” • “Our philosophical treatment of causation must make clear why the methods we use for testing causal claims provide good warrant for the uses to which we put those claims.” • Always emphasizing population studies as the basis of inferring causality in individual cases actually violates the pragmatic functions of causal theories. • Incorporating Sheils Jasanoff’s technology of humility, I argue for a pragmatic ethic of causal cognition in legal policy choices of causal theories.

20. Golkiewicz criteria on assessing factual causation in vaccination injury • Stevens v. Secretary of HHS (2001), Chief Special Master Golkiewicz proposed criteria for assessing factual causation: • Theory on the biological mechanism of vaccination injury • The petitioners present peer-reviewed literature that has shown that there is certain relationship between vaccination and the injury • The victim must present evidence demonstrating that the victims do have the injury • The petitioner must show that there is an acceptable temporal relationship between vaccination and injury • The petitioner has shown by preponderance of evidence that no reasonable evidence could support alternative causes of the injury • The circulate appeal court abolished the proposed criteria in Althen v. Secretary of HHS (2005): emphasizes case by case decisions

21. A debate about causation in a case of suspected post-vaccination harm in Taiwan • A 7-year-old boy with the surname Liu began to develop physical discomforts and even sepsis after receiving H1N1 flu vaccination. He diedeventually despite the treating hospital’s active treatment. The Liu boy’s father, a medical doctor, accused the hospital visiting staff of committing medical malpractice. • The pathological examination on the Liu boy’s tissue sample showed that his death was not related to the H1N1 vaccination. However, his father did not agree. His father proposed 8 questions that need further inquires and demand further overseas re-confirming examinations at institutes with high credibility. • Some medical experts also expressed their opinions that it is rare that the Liu boy’s death was related to the infection of B19 parvovirus. They thought there were still mysteries in the forensic examination reports.

22. Review of the factual causation in cases of post-vaccination harm • Public participation • Review committee could disclose its principles of determining individual causation and allow comments on the principles in civil society • It would be better to coherently incorporate the lay persons’ ideas on individual causation in maintaining a pragmatic expert discourse on causation • Aiming at creating a community-based factual causation criteria • Composition and transparency of the review committee • A balanced and fair composition of review committee members and the transparency of its deliberation process could enhance public trust in the decision of the review committee and ease the conflicts in determining causation in vaccination injury cases • Not over-representing the danger or safety of vaccines, the review committee could try to reflect a humane concern in determining causation in cases of vaccination injury

23. Causal cognition:An ethic of humanity and scientific humility • Not only individuals benefit from vaccination, the whole society also enjoys external benefit • In current political and epistemic economy, appealing to more better RCTs to solve the controversies in determining causation in post-vaccination harm is futile • The focus of reasoning should be shifted to the following questions: (1) what kind of evidence could be accepted? (2)who should bear the burden of proof? (3)how much belief probability is needed • The U.S. federal circulate appeal court made a dictum in Althen v. Secretary of HHS (2005):close calls regarding causation are resolved in favor of injured petitioners; that is, “preponderance of evidence” could be replaced by “benefit-of-the-doubt”

24. Preliminary conclusionsPragmatic causal cognition: • From 1986 to 2009, in Taiwan there were 407 applications for vaccination harm relief, 207 succeeded. However, as there is the new surge of vaccination injury cases and more emphasis on sound scientific evidence, what would happen? • The focus is not on moral blame, not on absolute “Truth” • The focus is on reaching a compensation policy of post-vaccination harm compensation • Aims: • The fair distribution of benefits and harms in society • Promoting the benefit of public health, and at the same time compensate those suffering harm in the process • To raise a huge barrier of causal cognition in the no-fault liability scheme is against humanity and scientific humility in addressing the suffering of those vulnerable in cognition, emotion and finance