TISSUE ENGINEERING: Part A Volume 20, Numbers 19 and 20, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/ten.tea.2013.0324
Liability Versus Innovation: The Legal Case for Regenerative Medicine Tsachi Keren-Paz, LLB, LLM, DJur,1 and Alicia J. El Haj, BSc, MSc, PhD 2
Medical innovation occupies a position somewhere between standard practice and clinical research, but innovation is primarily intended to benefit an individual patient where standard treatment fails. Medical innovations in the area of regenerative medicine have the potential to completely transform medical practice, but rely upon some major revision to the nature of treatments beyond drug-based therapies. There is considerable investment in scientific and clinical research, but further attention could be paid to legal barriers to medical innovation imposed by the threat of medical malpractice. We survey in this article the legal framework for making determinations of medical malpractice in general, and highlight the issues specific to innovative treatments. In essence, liability could be imposed for failing to adequately inform the patient about the innovative nature of the suggested therapy or based on the fact that the risks outweighed the benefits. As for the latter, we examine whether liability is likely to be based merely on deviating from existing practice or on an examination on the merits of the treatments’ risks and benefits. The facts that some risks are unforeseeable and some benefits are external to the patient complicate negligence determinations. The first fact relates to the problem of judging adverse events in hindsight; the second, to the obligation to make decisions based on the patient’s best interest and avoid conflict of interests. In addition, we evaluate the relationship between the obligations to secure the patient’s informed consent and to avoid clinical negligence. We identify the need for further research to examine the significance of the putative anti-innovation bias that current liability regimen has, and to examine whether a move to strict liability might avoid such bias, while being fair to patients who contribute for the advancement of medical knowledge by participating in innovative therapies.
Introduction
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tem cell therapy and regenerative medicine research produce innovative therapies. Significant government and private funding is supporting the development of new stem cell-based and acellular technologies worldwide. The aspiration is that this funding will make a significant impact on the health of the population, by aiding the development of new treatments. This manufacturing sector could also make a substantial contribution to the economy. Ultimately, cell-based therapies might replace the now declining pharmaceutical industry model. What stands in the way of these developments? Clearly, there are challenges in realizing these innovative products through the first stages of development and commercialization to the early first human trials, which will influence our ability to design and implement new research ideas. There is a disparity between the significant funding for blue sky research and for the development of new business models for these new treatments, and the much smaller
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funding for training and support of clinicians in a new era of healthcare treatments. The legal and medical framework that supports clinicians taking significant steps forward in novel healthcare treatments is fundamentally lacking. Can we deliver regenerative medical treatments without bridging this gap? In this article, we will focus on only one impediment to innovation—the threats posed by malpractice litigation on the development of innovative therapies. Whereas disciplinary proceedings pose another threat, perhaps even bigger, to innovation, we will not discuss this threat here, but its existence should be borne in mind when evaluating suggested reforms to legal liability. We hope that the lessons gleaned from the general legal framework regulating innovative therapies (beyond regenerative medicine) and the debate about the extent of defensive medicine and disincentive to innovate could identify a useful research agenda, which will be helpful in the regenerative medicine field. At the outset, it would be useful to stress that our inquiry is limited to innovative therapies rather than to research; the
School of Law, Keele University, Stoke-on-Trent, United Kingdom. Institute of Science and Technology in Medicine, Guy Hilton Research Centre, Keele University, Stoke-on-Trent, United Kingdom.
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regulatory framework and the scope or liability applicable to both are different. Innovative therapies are directed at helping the individual patient, while research is conducted for the purpose of gathering information to help future patients.1 Our ultimate aim is to identify if a change is required to ensure that clinicians get the necessary environment to bring healthcare innovation with all its medical, social, and economic benefits into the clinic, while at the same time ensuring that innovation is done responsibly, and that the legal outcome in litigation over injuries during innovative therapies is fair also to patients. There has been little litigation related to regenerative medicine innovations so far, and yet, there is still a significant conservatism in taking novel cell therapies or tissue engineering treatments to the clinic. Clearly, the potential stifling effect of legal liability on innovative therapy is not unique to regenerative medicine. We will first explain the legal framework governing determinations of medical malpractice in innovative settings. We will then note what further research is required, based on the inconclusive existing evidence about the stifling effects of tort law on innovation. The Legal Framework
Clinicians face two major legal risks: civil liability to the patient and professional disciplinary proceedings with their regulatory body—an example is the General Medical Council in the United Kingdom. Civil liability, in common law jurisdictions, is based mainly on the tort of negligence, which requires the patient to show that (1) she or he was owed a duty of care; (2) the duty was breached; (3) the breach is the factual and legal cause of the patient’s damage. Breach of duty could be manifested in either failing to secure the patient’s informed consent or in a clinical error. A tort is a civil wrong that unfairly causes someone else to suffer loss or harm resulting in legal liability for the person who commits the tortious act. Although the same act might be a crime as well as a tort, liability under the tort of negligence would not necessarily amount to criminal negligence. A lawsuit will enable the victim of the harm to recover their loss as damages. It is then reliant on the plaintiff in the lawsuit demonstrating that the actions or lack of action was the legally recognized cause of the harm. Since we do not focus on disciplinary proceedings here, we will not discuss decisions dealing with allegations of misconduct in the context of stem cells or regenerative medicine. We will also discuss the issue with a bias toward the United Kingdom as the legal framework varies considerably across the global regenerative community. However, using the United Kingdom as an example, we can explore some of the issues that have relevance across many clinical settings. Informed Consent
A patient should be provided with information about the nature of the treatment, the risks it entails, and the existence of alternative courses of action and their risks and benefits. Failure to provide the required information will lead to liability for the materialization of the risk, which was not adequately disclosed, even though the treatment suggested was the appropriate one and was conducted without negli-
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gence. A failure to secure the patient’s informed consent might raise causation difficulties,2 but this does not raise unique issues in the context of regenerative therapies. In the context of innovative therapies, courts across different jurisdictions seem to agree to the fact that the patient should be made aware that the treatment is innovative, alongside the uncertainties involved, and any commercial interest that the clinician might have in developing the innovative therapy.3,4 The last two factors justify an enhanced duty of disclosure in comparison to more traditional treatments5; the inherent uncertainties make it harder both to the physician and the patient before a decision is made and to the court after the injury has occurred to evaluate whether the benefits from the treatment outweigh its risks. A conflict of interests might affect the physician’s judgment about the appropriateness of using the innovative therapy, and regardless of commercial and reputational considerations, physicians may also have a bias in favor of experimenting to advance medical development.6 We refer to further factors that arguably call for heightened scrutiny of innovative therapies below. The current position seems to require an intermediate level of disclosure, which is arguably higher than what is required for traditional treatment but lower than what is required for participants in clinical research. This position has been attacked on opposite grounds. Parchomovsky and Stein have argued that the informed consent standards for conventional and innovative therapies should be the same across the board to prevent a comparative disadvantage of those offering innovative therapies7 (implicitly suggesting that the more stringent requirements applying for innovative therapies should apply to all treatments). Their approach, however, is based on an assumption that clinicians derive direct financial benefit from the treatments they offer, an assumption not always true across different health systems. It is likewise based on some controversial propositions such as that ‘‘the need to label the new treatment ‘experimental’ is likely to frighten away some patients by undermining their confidence in the treatment’’ and that doctors ‘‘should not be required to indiscriminately attach the ‘unknown’ label to all risks and benefits associated with innovative treatments.’’ The former claim is problematic since it suggests that it is legitimate to hide relevant information— that the treatment is innovative—to increase the patient’s participation; the latter, since the fact that the benefits and risks from innovative therapies are largely unknown is a relevant fact that should be brought to the patient’s attention. By contrast, Giesen has argued that the heightened standard of disclosure applied to research should be applied to innovative therapies as well.6 The more one buys into the existence of a fundamental difference between research and innovative therapies, based on the premise that the latter is intended to benefit the individual patient, whereas research is intended to accumulate knowledge about a treatment, the less justified it is to use the same standard of disclosure in both categories. The debate raises a number of questions for developing new therapies toward the clinic involving the choice of route through clinician-driven innovation versus commercial development. Clinical Negligence
Even if all the relevant information has been provided about the innovative treatment, a doctor might still be liable in negligence for the injury sustained from the treatment, if
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the treatment’s expected benefits could not justify its expected risks. There are several relevant distinctions in legal terms between choice and delivery of the treatments. For example, a basic distinction is between the claim that the decision to choose an innovative treatment was negligent and the claim that the way in which the treatment was performed was negligent. Negligent treatment does not differ between standard and innovative therapies, so will not be discussed here. All we can say about this distinction is that it is similar to a known distinction in products liability law between design defect and manufacturing defect. The potential scope of liability for the former is more far reaching, and accordingly, courts show a greater deference before they find that a product design is defective. (An example of this tendency could be found in the Restatement’s provisions about liability for prescription drugs and medical devices.8) It should be noted that, however, the potential scope of liability for a defective product is probably quite more significant compared with an innovative treatment, since by nature an innovative treatment is not a widespread practice and once it is proved to be dangerous it is not likely to be continued. So possibly, if what is behind courts’ relative reluctance to declare a design as defective is the potential crushing scope of liability, it might be that courts would show a greater tendency to view innovative treatments as negligent. A second distinction is between situations in which traditional treatment does not exist and situations in which it does. Possibly, courts are more likely to impose liability when the innovative treatment was not necessary since a traditional alternative existed, while the risks involved in the innovative treatment were not examined by a systematic clinical trial. It is here that the potential anti-innovation bias of the law is most prominent. As will be explained further below, as long as the innovative treatment has not been adopted by some peers, it is more prone to be characterized as negligent. However, in the absence of alternative treatment, an innovative treatment is less suspect; it less clearly deviates from established practice, since such practice does not exist. So, for example, in Hepworth v Kerr,9 reducing the blood pressure during operation to levels much lower than accepted as safe, to create a virtually blood-free operation site, was considered as negligent, since achieving this low level of bleeding seemed unnecessary and did not justify exposing patients to the extra risk of reducing their blood pressure to such a low level. In contrast, in Simms v Simms,10 the absence of any known treatment to the variant Creutzfeldt–Jakob disease led the court into approving the innovative treatment on the two children. It should be recalled that, however, Simms represents a rare occasion in which the court makes an ex-ante decision about whether the suggested treatment is appropriate and, as such, is free from the common hindsight bias according to which courts judge whether the treatment was appropriate after the risk has materialized and, therefore, are more likely to find (wrongly) that the treatment was negligent. A third entailed distinction is between negligence in simply departing from received wisdom and in the selection of the specific method. In some cases, any deviation might be negligent, while in others, the problem is not with the deviation itself, but rather with choosing from a number of alternatives an option clearly inferior to other innovative
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alternatives. Examples also include where the negligence seemed to be manifested in having inadequate validation techniques, which suggests that, at least implicitly, more appropriate validation techniques were available. A significant emphasis has been placed in regenerative medicine on the establishment and validation metrics associated with outcomes from cell-based therapies, which would, in part, strengthen the choices for treatment. This third distinction has some resemblance to the first; the negligence is not based on merely the policy decision to innovate, but rather on the operational decision of how to innovate. This difference between the two categories is that the decision of which option to choose involves discretion in a way that a poor performance of procedure does not. The Role of Cost–Benefit Analysis Versus Deviation from Custom
The fourth distinction is at the heart of medical malpractice litigation. Generally in tort law, a finding of negligence is based on a cost–benefit analysis concluding that the expected risks from the activity outweighed the activity’s benefits, so it was unjustified to undergo the activity. This decision is made based on the substantive evaluation of the activity’s cost–benefit portfolio. However, as a shorthand, courts at times rely on adherence to custom as a proof of reasonableness, and as a corollary, of deviation as proof of negligence.7,11,12 In the context of innovative therapies, then, the question is whether courts determine negligence based on substantive comparison of the treatment’s risks and benefits or based on the fact that treatment did not conform with accepted practice. To complete the picture, two additional conditions should be mentioned. First, custom is not only the majority custom; so, as long as there is a minority group considered to be as the responsible body to which the treatment adheres, there should be no liability. The problem in the context of innovation is that for truly innovative treatments, there would not be even a minority practice to which the treatment adheres. Someone, ultimately, has to be the first. Moreover, if the treatment is innovative, it might take some time before the minority clinicians practicing it would be considered to be a responsible body. The second condition is that deviation from professional guidelines is a prima facie (although not conclusive) indication of negligence.13 To the extent that professional guidelines do not accommodate the possibility of an innovative treatment (a likely possibility, given the fact that innovative treatment by nature has not gained yet an orthodox status), this too, might put those practicing innovative treatments at disadvantage. In the United Kingdom, the NICE (National Institute for Clinical Excellence) guidelines form such a professional guideline that advises on clinical practice. Seemingly, then, innovative therapies should be judged based on substantive examination of risks and benefits without a presumption that such deviation is negligent. If indeed, this is the way courts operate, the anti-innovation bias is less serious than one might think. In cases in which the innovative treatment has not been performed by other practitioners but the defendant brings expert evidence supporting the practice, is the court bound to accept this evidence or could it simply prefer the claimant’s expert evidence
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that the treatment was too risky? There is some evidence that English courts adapt to the context of innovative treatments out of concern not to stifle innovation despite being aware there is no recognized practice supporting these innovative treatments.10 Unforeseeable Risks to the Patient and Foreseeable Benefits to Third Parties
Turning to the substantive evaluation of risks and benefits, two issues arise. Determinations of negligence ought to be based merely on the foreseeable risks and benefits. However, an ex-post evaluation of the decision after the risk has materialized exposes the defendant to a risk of erroneous finding of negligence. While courts’ decisions include rhetoric warning against hindsight bias,14,15 there is room to suspect, and research reveals that hindsight bias does exist.16,17 This problem is especially acute in innovative therapy cases, since such treatments are bound to involve many unforeseeable risks. Given the considerable reputation costs to physicians found negligent, the hindsight bias problem is likely to add to tort law’s alleged anti-innovation bias. This relates to the second issue of whether foreseeable benefits to nonpatients should be taken into account in negligence determinations. In general, courts take into account the fact that alternative course of action to that alleged as negligent would risk third parties (and obviously the claimants themselves) in determination of negligence18–20 although some dispute this account.21 However, the obligation to act in the patient’s best interest seemingly excludes consideration of nonpatient benefits in determinations of liability. Indeed, what separates innovative therapies from research is that the former is directed at helping the individual patient, rather than gathering information to help future patients. This suggests that in determinations whether to try an innovative therapy on a patient, outside of a clinical trial, only benefits to the patient should be taken into account. A commitment to make decisions based only on the patient’s best interests appears also in Section 1(8)(a) of the recent Medical Innovation Bill.22 Innovative treatments involve benefits to the society, potential future patients, the clinicians involved in the experimental innovative therapy, and the scientific community. Given the fact that innovative therapies clearly benefit third parties, a number of questions arise, for example, do clinicians recommend (and patients accept) innovative therapies based on merely the patient’s best interests or also based on potential benefits to third parties? If the latter, is this done in a transparent way? If so, is this likely to lead to a finding of malpractice? While courts’ rhetoric is likely to insist that only benefits to the patient count, it is possible (but very hard to verify or refute) that nonpatient benefits lead to a finding that the innovative therapy was not negligent. Ought we to limit the cost– benefit calculus to the patient’s best interests? Views on this point in the literature differ. On one side of the spectrum one can find followers of economic analysis of law supporting a shift to comprehensive cost–benefit analysis.7 It has been suggested that whenever the defendant is negligent, but an alternative course of action would have risked the claimant, third parties, and even society at large, the benefits to those not being exposed to the risk from the alternative course of
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action should reduce the defendant’s liability.20 Without sufficient guarantee against the risks of malpractice liability, much innovative work, such as the use of penicillin or performing heart transplant surgery, would not have been attempted. On the other side, some conceive of external benefits as manifestation of conflict of interests, which justifies a heightened scrutiny of innovative therapies in comparison to conventional treatments.5,6 Any plausible case suggesting that negligence determinations should not be limited to the patient’s best interests would lead to fewer findings of negligence. At the same time, taking the wider societal benefits (positive externalities, in economists’ lingo) into account strengthens the case for strict liability towards the patient based on notions of fair distribution of risks and benefits.23 An extremely important point is that the structure of risks and benefits in innovative therapies is asymmetrical since ‘‘all the uncertain risks associated with the innovation will unequivocally be borne by the patient, not the physician.’’5 Beyond the question whether innovative therapies justify higher scrutiny by the courts in making negligence determinations, the patient’s involvement in the production of such external benefits might justify strict liability toward the patient. From the physician’s perspective, as long as liability is not based on fault, the costs are not probative since they are either borne by the employer/sponsor, or, if by the insurer, premiums usually are not experience based.24 Moreover, to an extent varying with the way the healthcare system is funded, the physician is a good proxy for the benefit received by future patients and the scientific community.25 Appreciating the fact that the wider societal benefits are produced by both the physician and patient might then justify a move from negligence-based liability to strict liability. Heightened Scrutiny of Innovative Therapies?
As we have just seen, there are different views on whether a heightened level of scrutiny is justified. Pro-innovation scholars oppose heightened scrutiny on welfarist grounds.7 Pro-patient scholars support it out of concern for patients’ interests and rights. Reasons that support greater scrutiny are that innovative therapies have not passed scientific scrutiny and the potential for conflict of interests.5 This assumes that courts can employ a greater scrutiny of such treatments despite the built-in uncertainty involved in innovative therapies, the existence of unforeseeable risks, and the absence of a clear benchmark to judge against the innovative therapy. Assuming courts ought to employ greater scrutiny of innovative therapies within a negligence framework, how could this be done? Is it by accepting that, what seems to be discredited now, a mere deviation from custom is presumptively negligent26; by applying special rules to the evaluation of expert evidence about the reasonableness of the impinged treatment; or by excluding benefits and including risks, as part of a substantive evaluation of the treatment, in a manner different from what courts do a regular case? The Relationship Between Informed Consent and Clinical Negligence
Finally, there is the question of to what extent an ex-post second-guessing of the treatment’s cost–benefit portfolio is justified when full disclosure of the relevant information was given: the innovative nature of the treatment, its risks,
LIABILITY VS. INNOVATION
and the fact that some of the risks are probably unknown. There are weighty arguments on both sides: on the one hand, to the general skepticism about the usefulness of the informed consent doctrine based on asymmetrical knowledge and the power gaps between the parties, and on the patient’s inability to understand and assess the risks properly,27–29 one can add that it is meaningless to expect patients to understand the significance of unknown risks. There are several factors undermining patients’ consent as sufficient control mechanism of innovative therapies: the patient’s irrational hope that the treatment would work; bias by the clinician who overestimates the chances of success; and even pressure by the patient to try a last resort treatment. These considerations are in effect paternalistic and then one is forced to evaluate whether paternalism in such context is justified or not. Especially in cases in which the patient has no therapeutic alternative, there is a strong argument for limiting findings of liability to breach of the obligation to receive the patient’s informed consent. As mentioned above, the question is in essence the degree to which paternalism is justified in this context, and reasonable views could differ on this. One might oppose the suggestion that there should be no substantive evaluation of the reasonableness of the innovative therapy, provided informed consent has been secured, based on the fact that futile treatments are socially undesirable. However, there are two responses to this concern. First, the fact that the treatment is futile (or unexpectedly risky) is known only in hindsight. The point of innovative therapies is exactly that there is a small chance of success; so, not to stifle useful innovation, we have to bear the costs of unsuccessful attempts to innovate. The more concerned one with hindsight bias is, the more leeway should be given to failed innovative treatments that offered ex-ante low success rates. Moreover, especially given the clinician’s incentives to innovate, which are external to the patient’s best interests, the clinician might be better situated to assess whether the treatment is futile before the treatment is given, rather than the court is, ex-post. The interest in controlling costs of futile treatments is better left to other forms of regulation such as hospital Clinical Governance Committees.
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innovation is reduced and defensive medicine is practiced will vary from one area of medicine to another. Therefore, a careful examination is needed of regenerative medicine’s regulatory and mark structures, to find out the extent to which fear from liability stifles innovation. Ultimately, our aspiration is to provide a clearer legal framework to support engagement of more clinicians keen to adopt new technologies and therapies in regenerative medicine. Acknowledgments
This work had been funded by an EPSRC Bridging the Gaps Programme. A.E.H. is a holder of a Royal Society Merit Award. John Rumbold has provided limited research assistance for this project. Disclosure Statement
No competing financial interests exist. References
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
Does the Law Stifle Innovation in Regenerative Medicine? The Need for Further Evidence
In conclusion, whether the threat of tort law stifles innovation and to what extent is an empirical question and the answer to it is unclear. An anti-innovation bias is but one aspect of the broader debate of whether the law (especially tort law) causes defensive medicine. Defensive medicine has several subtly different definitions, but for current purposes can be summarized as practice intended to minimize the physician’s exposure to liability, rather than to provide optimal care to the patient. It could be manifested by either doing too much (e.g., prescribing unnecessary medicine, opting for caesarean section when it is clinically unjustified) or too little (e.g., avoiding high risk, yet beneficial procedures, including innovative ones, and opting out from high-risk professions such as obstetrics).30 While arguments exist that tort law stifles innovation in medicine and product design,7 the empirical evidence is inconclusive.31–33 We do need further evidence on the relationship between law and innovation, both in general and in the context of regenerative medicine. The extent to which
14. 15. 16. 17. 18. 19. 20. 21. 22. 23.
Walker-Smith v GMC [2012] EWHC 503 (Admin). Chester v Afshar [2004] UKHL 41. Estrada v Jacques 321 SE 2d 240 [1984] at 255 (CA, NC). Zimmer v Ringrose [1981] 124 DLR (3d) 215. Chan, T.E. Legal and regulatory responses to innovative treatment. Med Law Rev 21, 92, 2013. Giesen, D. Civil liability of physicians for new methods of treatment and experimentation: a comparative examination. Med Law Rev 3, 22, 1995. Parchomovsky, G., and Stein, A. Torts and innovation. Mich Law Rev 107, 285, 2008. Restatement (Third) of Torts: Products Liability x 6 cmt. b [1998]. Hepworth v Kerr [1995] 6 Medical Law Reports 139 (QBD, Sheffield). Simms v Simms, A v A (A Child) [2002] EWHC 2734 (Fam). Bolam v Friern Hospital Management Committee [1957] 1 W.L.R. Bolitho v City and Hackney HA [1993] 4 Medical Law Reports 381. Samanta, A., Mello, M.M., Foster, C., Tingle, J., and Samanta, J. The role of clinical guidelines in medical negligence litigation: a shift from the Bolam standard. Med Law Rev 14, 321, 2006. Roe v Minister of Health [1954] 2 All ER 131. Bolton v Stone [1951] A.C. 850. LaBine, S., and LaBine, G. Determinations of negligence and the hindsight bias. Law & Human Behavior 20, 501, 1996. Rachlinski, J.J. A Positive Psychological Theory of Judging in Hindsight. University of Chicago Law Review 65, 571, 1998. Watt v Hertfordshire [1954] 1 WLR 835. Keren-Paz, T. Torts, Egalitarianism and Distributive Justice. Aldershot, United Kingdom: Ashgate, 2007. Porat, A. Offsetting risks. Mich Law Rev 106, 243, 20. Wright, R. The standards of care in negligence law. In: Owen, D, ed. Philosophical Foundations of Tort Law. Oxford: Clarendon Press, 1995, pp. 249–275. Medical Innovation Bill 2014 (HL Bill 4) http://services .parliament.uk/bills/2014-15/medicalinnovation.html. Keating, G. Distributive and corrective justice in the tort law of accidents. S Calif Law Rev 74, 193, 2000.
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24. Keren-Paz, T. Liability regimes, reputation loss, and defensive medicine. Med Law Rev 18, 363, 2010. 25. Keren-Paz, T. Injuries from unforeseeable risks which advance medical knowledge—a restitution-based justification for strict liability. J of European Tort Law. Forthcoming 2014–2015. 26. Hunter v Hanley [1955] SC 200 (Scotland). 27. Kelly, A. Research and the subject: the practice of informed consent. Pol Leg Anthropol Rev 26, 182, 2003. 28. Emanuel, E.J. The Ends of Human Life: Medical Ethics in a Liberal Polity. Cambridge: Harvard University Press, 1991. 29. Roy, D., Dickens, B., and Williams, J. Bioethics in Canada. Scarborough: Prentice Hall, 1994. 30. Anderson, R.E. Billions for defense: the pervasive nature of defensive medicine. Arch Intern Med 159, 2399, 1999. 31. Viscusi, K., and Moore, M.J. Product liability, research and development, and innovation. J Pol Economy 101, 161, 1993. 32. Huber, P.W., and Litan, R.E., eds. The Liability Maze: The Impact of Liability Law on Safety and Innovation. Washington, DC: Brookings Institution, 1991. 33. Tancredi, L., and Nelkin, D. Medical malpractice and its effect on innovation. In: Huber, P.W., and Litan, R.E., eds.
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The Liability Maze: The Impact of Liability Law on Safety and Innovation. Washington, DC: Brookings Institution, 1991, pp. 251–273.
Address correspondence to: Alicia J. El Haj, BSc, MSc, PhD Institute of Science and Technology in Medicine Guy Hilton Research Centre Keele University Thornburrow Drive Hartshill Stoke-on-Trent ST4 7QB United Kingdom E-mail: [email protected] Received: June 3, 2013 Accepted: June 9, 2014 Online Publication Date: July 21, 2014
Liability Versus Innovation: The Legal Case for Regenerative Medicine Tsachi Keren-Paz, LLB, LLM, DJur,1 and Alicia J. El Haj, BSc, MSc, PhD 2
Medical innovation occupies a position somewhere between standard practice and clinical research, but innovation is primarily intended to benefit an individual patient where standard treatment fails. Medical innovations in the area of regenerative medicine have the potential to completely transform medical practice, but rely upon some major revision to the nature of treatments beyond drug-based therapies. There is considerable investment in scientific and clinical research, but further attention could be paid to legal barriers to medical innovation imposed by the threat of medical malpractice. We survey in this article the legal framework for making determinations of medical malpractice in general, and highlight the issues specific to innovative treatments. In essence, liability could be imposed for failing to adequately inform the patient about the innovative nature of the suggested therapy or based on the fact that the risks outweighed the benefits. As for the latter, we examine whether liability is likely to be based merely on deviating from existing practice or on an examination on the merits of the treatments’ risks and benefits. The facts that some risks are unforeseeable and some benefits are external to the patient complicate negligence determinations. The first fact relates to the problem of judging adverse events in hindsight; the second, to the obligation to make decisions based on the patient’s best interest and avoid conflict of interests. In addition, we evaluate the relationship between the obligations to secure the patient’s informed consent and to avoid clinical negligence. We identify the need for further research to examine the significance of the putative anti-innovation bias that current liability regimen has, and to examine whether a move to strict liability might avoid such bias, while being fair to patients who contribute for the advancement of medical knowledge by participating in innovative therapies.
Introduction
S
tem cell therapy and regenerative medicine research produce innovative therapies. Significant government and private funding is supporting the development of new stem cell-based and acellular technologies worldwide. The aspiration is that this funding will make a significant impact on the health of the population, by aiding the development of new treatments. This manufacturing sector could also make a substantial contribution to the economy. Ultimately, cell-based therapies might replace the now declining pharmaceutical industry model. What stands in the way of these developments? Clearly, there are challenges in realizing these innovative products through the first stages of development and commercialization to the early first human trials, which will influence our ability to design and implement new research ideas. There is a disparity between the significant funding for blue sky research and for the development of new business models for these new treatments, and the much smaller
1 2
funding for training and support of clinicians in a new era of healthcare treatments. The legal and medical framework that supports clinicians taking significant steps forward in novel healthcare treatments is fundamentally lacking. Can we deliver regenerative medical treatments without bridging this gap? In this article, we will focus on only one impediment to innovation—the threats posed by malpractice litigation on the development of innovative therapies. Whereas disciplinary proceedings pose another threat, perhaps even bigger, to innovation, we will not discuss this threat here, but its existence should be borne in mind when evaluating suggested reforms to legal liability. We hope that the lessons gleaned from the general legal framework regulating innovative therapies (beyond regenerative medicine) and the debate about the extent of defensive medicine and disincentive to innovate could identify a useful research agenda, which will be helpful in the regenerative medicine field. At the outset, it would be useful to stress that our inquiry is limited to innovative therapies rather than to research; the
School of Law, Keele University, Stoke-on-Trent, United Kingdom. Institute of Science and Technology in Medicine, Guy Hilton Research Centre, Keele University, Stoke-on-Trent, United Kingdom.
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regulatory framework and the scope or liability applicable to both are different. Innovative therapies are directed at helping the individual patient, while research is conducted for the purpose of gathering information to help future patients.1 Our ultimate aim is to identify if a change is required to ensure that clinicians get the necessary environment to bring healthcare innovation with all its medical, social, and economic benefits into the clinic, while at the same time ensuring that innovation is done responsibly, and that the legal outcome in litigation over injuries during innovative therapies is fair also to patients. There has been little litigation related to regenerative medicine innovations so far, and yet, there is still a significant conservatism in taking novel cell therapies or tissue engineering treatments to the clinic. Clearly, the potential stifling effect of legal liability on innovative therapy is not unique to regenerative medicine. We will first explain the legal framework governing determinations of medical malpractice in innovative settings. We will then note what further research is required, based on the inconclusive existing evidence about the stifling effects of tort law on innovation. The Legal Framework
Clinicians face two major legal risks: civil liability to the patient and professional disciplinary proceedings with their regulatory body—an example is the General Medical Council in the United Kingdom. Civil liability, in common law jurisdictions, is based mainly on the tort of negligence, which requires the patient to show that (1) she or he was owed a duty of care; (2) the duty was breached; (3) the breach is the factual and legal cause of the patient’s damage. Breach of duty could be manifested in either failing to secure the patient’s informed consent or in a clinical error. A tort is a civil wrong that unfairly causes someone else to suffer loss or harm resulting in legal liability for the person who commits the tortious act. Although the same act might be a crime as well as a tort, liability under the tort of negligence would not necessarily amount to criminal negligence. A lawsuit will enable the victim of the harm to recover their loss as damages. It is then reliant on the plaintiff in the lawsuit demonstrating that the actions or lack of action was the legally recognized cause of the harm. Since we do not focus on disciplinary proceedings here, we will not discuss decisions dealing with allegations of misconduct in the context of stem cells or regenerative medicine. We will also discuss the issue with a bias toward the United Kingdom as the legal framework varies considerably across the global regenerative community. However, using the United Kingdom as an example, we can explore some of the issues that have relevance across many clinical settings. Informed Consent
A patient should be provided with information about the nature of the treatment, the risks it entails, and the existence of alternative courses of action and their risks and benefits. Failure to provide the required information will lead to liability for the materialization of the risk, which was not adequately disclosed, even though the treatment suggested was the appropriate one and was conducted without negli-
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gence. A failure to secure the patient’s informed consent might raise causation difficulties,2 but this does not raise unique issues in the context of regenerative therapies. In the context of innovative therapies, courts across different jurisdictions seem to agree to the fact that the patient should be made aware that the treatment is innovative, alongside the uncertainties involved, and any commercial interest that the clinician might have in developing the innovative therapy.3,4 The last two factors justify an enhanced duty of disclosure in comparison to more traditional treatments5; the inherent uncertainties make it harder both to the physician and the patient before a decision is made and to the court after the injury has occurred to evaluate whether the benefits from the treatment outweigh its risks. A conflict of interests might affect the physician’s judgment about the appropriateness of using the innovative therapy, and regardless of commercial and reputational considerations, physicians may also have a bias in favor of experimenting to advance medical development.6 We refer to further factors that arguably call for heightened scrutiny of innovative therapies below. The current position seems to require an intermediate level of disclosure, which is arguably higher than what is required for traditional treatment but lower than what is required for participants in clinical research. This position has been attacked on opposite grounds. Parchomovsky and Stein have argued that the informed consent standards for conventional and innovative therapies should be the same across the board to prevent a comparative disadvantage of those offering innovative therapies7 (implicitly suggesting that the more stringent requirements applying for innovative therapies should apply to all treatments). Their approach, however, is based on an assumption that clinicians derive direct financial benefit from the treatments they offer, an assumption not always true across different health systems. It is likewise based on some controversial propositions such as that ‘‘the need to label the new treatment ‘experimental’ is likely to frighten away some patients by undermining their confidence in the treatment’’ and that doctors ‘‘should not be required to indiscriminately attach the ‘unknown’ label to all risks and benefits associated with innovative treatments.’’ The former claim is problematic since it suggests that it is legitimate to hide relevant information— that the treatment is innovative—to increase the patient’s participation; the latter, since the fact that the benefits and risks from innovative therapies are largely unknown is a relevant fact that should be brought to the patient’s attention. By contrast, Giesen has argued that the heightened standard of disclosure applied to research should be applied to innovative therapies as well.6 The more one buys into the existence of a fundamental difference between research and innovative therapies, based on the premise that the latter is intended to benefit the individual patient, whereas research is intended to accumulate knowledge about a treatment, the less justified it is to use the same standard of disclosure in both categories. The debate raises a number of questions for developing new therapies toward the clinic involving the choice of route through clinician-driven innovation versus commercial development. Clinical Negligence
Even if all the relevant information has been provided about the innovative treatment, a doctor might still be liable in negligence for the injury sustained from the treatment, if
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the treatment’s expected benefits could not justify its expected risks. There are several relevant distinctions in legal terms between choice and delivery of the treatments. For example, a basic distinction is between the claim that the decision to choose an innovative treatment was negligent and the claim that the way in which the treatment was performed was negligent. Negligent treatment does not differ between standard and innovative therapies, so will not be discussed here. All we can say about this distinction is that it is similar to a known distinction in products liability law between design defect and manufacturing defect. The potential scope of liability for the former is more far reaching, and accordingly, courts show a greater deference before they find that a product design is defective. (An example of this tendency could be found in the Restatement’s provisions about liability for prescription drugs and medical devices.8) It should be noted that, however, the potential scope of liability for a defective product is probably quite more significant compared with an innovative treatment, since by nature an innovative treatment is not a widespread practice and once it is proved to be dangerous it is not likely to be continued. So possibly, if what is behind courts’ relative reluctance to declare a design as defective is the potential crushing scope of liability, it might be that courts would show a greater tendency to view innovative treatments as negligent. A second distinction is between situations in which traditional treatment does not exist and situations in which it does. Possibly, courts are more likely to impose liability when the innovative treatment was not necessary since a traditional alternative existed, while the risks involved in the innovative treatment were not examined by a systematic clinical trial. It is here that the potential anti-innovation bias of the law is most prominent. As will be explained further below, as long as the innovative treatment has not been adopted by some peers, it is more prone to be characterized as negligent. However, in the absence of alternative treatment, an innovative treatment is less suspect; it less clearly deviates from established practice, since such practice does not exist. So, for example, in Hepworth v Kerr,9 reducing the blood pressure during operation to levels much lower than accepted as safe, to create a virtually blood-free operation site, was considered as negligent, since achieving this low level of bleeding seemed unnecessary and did not justify exposing patients to the extra risk of reducing their blood pressure to such a low level. In contrast, in Simms v Simms,10 the absence of any known treatment to the variant Creutzfeldt–Jakob disease led the court into approving the innovative treatment on the two children. It should be recalled that, however, Simms represents a rare occasion in which the court makes an ex-ante decision about whether the suggested treatment is appropriate and, as such, is free from the common hindsight bias according to which courts judge whether the treatment was appropriate after the risk has materialized and, therefore, are more likely to find (wrongly) that the treatment was negligent. A third entailed distinction is between negligence in simply departing from received wisdom and in the selection of the specific method. In some cases, any deviation might be negligent, while in others, the problem is not with the deviation itself, but rather with choosing from a number of alternatives an option clearly inferior to other innovative
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alternatives. Examples also include where the negligence seemed to be manifested in having inadequate validation techniques, which suggests that, at least implicitly, more appropriate validation techniques were available. A significant emphasis has been placed in regenerative medicine on the establishment and validation metrics associated with outcomes from cell-based therapies, which would, in part, strengthen the choices for treatment. This third distinction has some resemblance to the first; the negligence is not based on merely the policy decision to innovate, but rather on the operational decision of how to innovate. This difference between the two categories is that the decision of which option to choose involves discretion in a way that a poor performance of procedure does not. The Role of Cost–Benefit Analysis Versus Deviation from Custom
The fourth distinction is at the heart of medical malpractice litigation. Generally in tort law, a finding of negligence is based on a cost–benefit analysis concluding that the expected risks from the activity outweighed the activity’s benefits, so it was unjustified to undergo the activity. This decision is made based on the substantive evaluation of the activity’s cost–benefit portfolio. However, as a shorthand, courts at times rely on adherence to custom as a proof of reasonableness, and as a corollary, of deviation as proof of negligence.7,11,12 In the context of innovative therapies, then, the question is whether courts determine negligence based on substantive comparison of the treatment’s risks and benefits or based on the fact that treatment did not conform with accepted practice. To complete the picture, two additional conditions should be mentioned. First, custom is not only the majority custom; so, as long as there is a minority group considered to be as the responsible body to which the treatment adheres, there should be no liability. The problem in the context of innovation is that for truly innovative treatments, there would not be even a minority practice to which the treatment adheres. Someone, ultimately, has to be the first. Moreover, if the treatment is innovative, it might take some time before the minority clinicians practicing it would be considered to be a responsible body. The second condition is that deviation from professional guidelines is a prima facie (although not conclusive) indication of negligence.13 To the extent that professional guidelines do not accommodate the possibility of an innovative treatment (a likely possibility, given the fact that innovative treatment by nature has not gained yet an orthodox status), this too, might put those practicing innovative treatments at disadvantage. In the United Kingdom, the NICE (National Institute for Clinical Excellence) guidelines form such a professional guideline that advises on clinical practice. Seemingly, then, innovative therapies should be judged based on substantive examination of risks and benefits without a presumption that such deviation is negligent. If indeed, this is the way courts operate, the anti-innovation bias is less serious than one might think. In cases in which the innovative treatment has not been performed by other practitioners but the defendant brings expert evidence supporting the practice, is the court bound to accept this evidence or could it simply prefer the claimant’s expert evidence
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that the treatment was too risky? There is some evidence that English courts adapt to the context of innovative treatments out of concern not to stifle innovation despite being aware there is no recognized practice supporting these innovative treatments.10 Unforeseeable Risks to the Patient and Foreseeable Benefits to Third Parties
Turning to the substantive evaluation of risks and benefits, two issues arise. Determinations of negligence ought to be based merely on the foreseeable risks and benefits. However, an ex-post evaluation of the decision after the risk has materialized exposes the defendant to a risk of erroneous finding of negligence. While courts’ decisions include rhetoric warning against hindsight bias,14,15 there is room to suspect, and research reveals that hindsight bias does exist.16,17 This problem is especially acute in innovative therapy cases, since such treatments are bound to involve many unforeseeable risks. Given the considerable reputation costs to physicians found negligent, the hindsight bias problem is likely to add to tort law’s alleged anti-innovation bias. This relates to the second issue of whether foreseeable benefits to nonpatients should be taken into account in negligence determinations. In general, courts take into account the fact that alternative course of action to that alleged as negligent would risk third parties (and obviously the claimants themselves) in determination of negligence18–20 although some dispute this account.21 However, the obligation to act in the patient’s best interest seemingly excludes consideration of nonpatient benefits in determinations of liability. Indeed, what separates innovative therapies from research is that the former is directed at helping the individual patient, rather than gathering information to help future patients. This suggests that in determinations whether to try an innovative therapy on a patient, outside of a clinical trial, only benefits to the patient should be taken into account. A commitment to make decisions based only on the patient’s best interests appears also in Section 1(8)(a) of the recent Medical Innovation Bill.22 Innovative treatments involve benefits to the society, potential future patients, the clinicians involved in the experimental innovative therapy, and the scientific community. Given the fact that innovative therapies clearly benefit third parties, a number of questions arise, for example, do clinicians recommend (and patients accept) innovative therapies based on merely the patient’s best interests or also based on potential benefits to third parties? If the latter, is this done in a transparent way? If so, is this likely to lead to a finding of malpractice? While courts’ rhetoric is likely to insist that only benefits to the patient count, it is possible (but very hard to verify or refute) that nonpatient benefits lead to a finding that the innovative therapy was not negligent. Ought we to limit the cost– benefit calculus to the patient’s best interests? Views on this point in the literature differ. On one side of the spectrum one can find followers of economic analysis of law supporting a shift to comprehensive cost–benefit analysis.7 It has been suggested that whenever the defendant is negligent, but an alternative course of action would have risked the claimant, third parties, and even society at large, the benefits to those not being exposed to the risk from the alternative course of
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action should reduce the defendant’s liability.20 Without sufficient guarantee against the risks of malpractice liability, much innovative work, such as the use of penicillin or performing heart transplant surgery, would not have been attempted. On the other side, some conceive of external benefits as manifestation of conflict of interests, which justifies a heightened scrutiny of innovative therapies in comparison to conventional treatments.5,6 Any plausible case suggesting that negligence determinations should not be limited to the patient’s best interests would lead to fewer findings of negligence. At the same time, taking the wider societal benefits (positive externalities, in economists’ lingo) into account strengthens the case for strict liability towards the patient based on notions of fair distribution of risks and benefits.23 An extremely important point is that the structure of risks and benefits in innovative therapies is asymmetrical since ‘‘all the uncertain risks associated with the innovation will unequivocally be borne by the patient, not the physician.’’5 Beyond the question whether innovative therapies justify higher scrutiny by the courts in making negligence determinations, the patient’s involvement in the production of such external benefits might justify strict liability toward the patient. From the physician’s perspective, as long as liability is not based on fault, the costs are not probative since they are either borne by the employer/sponsor, or, if by the insurer, premiums usually are not experience based.24 Moreover, to an extent varying with the way the healthcare system is funded, the physician is a good proxy for the benefit received by future patients and the scientific community.25 Appreciating the fact that the wider societal benefits are produced by both the physician and patient might then justify a move from negligence-based liability to strict liability. Heightened Scrutiny of Innovative Therapies?
As we have just seen, there are different views on whether a heightened level of scrutiny is justified. Pro-innovation scholars oppose heightened scrutiny on welfarist grounds.7 Pro-patient scholars support it out of concern for patients’ interests and rights. Reasons that support greater scrutiny are that innovative therapies have not passed scientific scrutiny and the potential for conflict of interests.5 This assumes that courts can employ a greater scrutiny of such treatments despite the built-in uncertainty involved in innovative therapies, the existence of unforeseeable risks, and the absence of a clear benchmark to judge against the innovative therapy. Assuming courts ought to employ greater scrutiny of innovative therapies within a negligence framework, how could this be done? Is it by accepting that, what seems to be discredited now, a mere deviation from custom is presumptively negligent26; by applying special rules to the evaluation of expert evidence about the reasonableness of the impinged treatment; or by excluding benefits and including risks, as part of a substantive evaluation of the treatment, in a manner different from what courts do a regular case? The Relationship Between Informed Consent and Clinical Negligence
Finally, there is the question of to what extent an ex-post second-guessing of the treatment’s cost–benefit portfolio is justified when full disclosure of the relevant information was given: the innovative nature of the treatment, its risks,
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and the fact that some of the risks are probably unknown. There are weighty arguments on both sides: on the one hand, to the general skepticism about the usefulness of the informed consent doctrine based on asymmetrical knowledge and the power gaps between the parties, and on the patient’s inability to understand and assess the risks properly,27–29 one can add that it is meaningless to expect patients to understand the significance of unknown risks. There are several factors undermining patients’ consent as sufficient control mechanism of innovative therapies: the patient’s irrational hope that the treatment would work; bias by the clinician who overestimates the chances of success; and even pressure by the patient to try a last resort treatment. These considerations are in effect paternalistic and then one is forced to evaluate whether paternalism in such context is justified or not. Especially in cases in which the patient has no therapeutic alternative, there is a strong argument for limiting findings of liability to breach of the obligation to receive the patient’s informed consent. As mentioned above, the question is in essence the degree to which paternalism is justified in this context, and reasonable views could differ on this. One might oppose the suggestion that there should be no substantive evaluation of the reasonableness of the innovative therapy, provided informed consent has been secured, based on the fact that futile treatments are socially undesirable. However, there are two responses to this concern. First, the fact that the treatment is futile (or unexpectedly risky) is known only in hindsight. The point of innovative therapies is exactly that there is a small chance of success; so, not to stifle useful innovation, we have to bear the costs of unsuccessful attempts to innovate. The more concerned one with hindsight bias is, the more leeway should be given to failed innovative treatments that offered ex-ante low success rates. Moreover, especially given the clinician’s incentives to innovate, which are external to the patient’s best interests, the clinician might be better situated to assess whether the treatment is futile before the treatment is given, rather than the court is, ex-post. The interest in controlling costs of futile treatments is better left to other forms of regulation such as hospital Clinical Governance Committees.
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innovation is reduced and defensive medicine is practiced will vary from one area of medicine to another. Therefore, a careful examination is needed of regenerative medicine’s regulatory and mark structures, to find out the extent to which fear from liability stifles innovation. Ultimately, our aspiration is to provide a clearer legal framework to support engagement of more clinicians keen to adopt new technologies and therapies in regenerative medicine. Acknowledgments
This work had been funded by an EPSRC Bridging the Gaps Programme. A.E.H. is a holder of a Royal Society Merit Award. John Rumbold has provided limited research assistance for this project. Disclosure Statement
No competing financial interests exist. References
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
Does the Law Stifle Innovation in Regenerative Medicine? The Need for Further Evidence
In conclusion, whether the threat of tort law stifles innovation and to what extent is an empirical question and the answer to it is unclear. An anti-innovation bias is but one aspect of the broader debate of whether the law (especially tort law) causes defensive medicine. Defensive medicine has several subtly different definitions, but for current purposes can be summarized as practice intended to minimize the physician’s exposure to liability, rather than to provide optimal care to the patient. It could be manifested by either doing too much (e.g., prescribing unnecessary medicine, opting for caesarean section when it is clinically unjustified) or too little (e.g., avoiding high risk, yet beneficial procedures, including innovative ones, and opting out from high-risk professions such as obstetrics).30 While arguments exist that tort law stifles innovation in medicine and product design,7 the empirical evidence is inconclusive.31–33 We do need further evidence on the relationship between law and innovation, both in general and in the context of regenerative medicine. The extent to which
14. 15. 16. 17. 18. 19. 20. 21. 22. 23.
Walker-Smith v GMC [2012] EWHC 503 (Admin). Chester v Afshar [2004] UKHL 41. Estrada v Jacques 321 SE 2d 240 [1984] at 255 (CA, NC). Zimmer v Ringrose [1981] 124 DLR (3d) 215. Chan, T.E. Legal and regulatory responses to innovative treatment. Med Law Rev 21, 92, 2013. Giesen, D. Civil liability of physicians for new methods of treatment and experimentation: a comparative examination. Med Law Rev 3, 22, 1995. Parchomovsky, G., and Stein, A. Torts and innovation. Mich Law Rev 107, 285, 2008. Restatement (Third) of Torts: Products Liability x 6 cmt. b [1998]. Hepworth v Kerr [1995] 6 Medical Law Reports 139 (QBD, Sheffield). Simms v Simms, A v A (A Child) [2002] EWHC 2734 (Fam). Bolam v Friern Hospital Management Committee [1957] 1 W.L.R. Bolitho v City and Hackney HA [1993] 4 Medical Law Reports 381. Samanta, A., Mello, M.M., Foster, C., Tingle, J., and Samanta, J. The role of clinical guidelines in medical negligence litigation: a shift from the Bolam standard. Med Law Rev 14, 321, 2006. Roe v Minister of Health [1954] 2 All ER 131. Bolton v Stone [1951] A.C. 850. LaBine, S., and LaBine, G. Determinations of negligence and the hindsight bias. Law & Human Behavior 20, 501, 1996. Rachlinski, J.J. A Positive Psychological Theory of Judging in Hindsight. University of Chicago Law Review 65, 571, 1998. Watt v Hertfordshire [1954] 1 WLR 835. Keren-Paz, T. Torts, Egalitarianism and Distributive Justice. Aldershot, United Kingdom: Ashgate, 2007. Porat, A. Offsetting risks. Mich Law Rev 106, 243, 20. Wright, R. The standards of care in negligence law. In: Owen, D, ed. Philosophical Foundations of Tort Law. Oxford: Clarendon Press, 1995, pp. 249–275. Medical Innovation Bill 2014 (HL Bill 4) http://services .parliament.uk/bills/2014-15/medicalinnovation.html. Keating, G. Distributive and corrective justice in the tort law of accidents. S Calif Law Rev 74, 193, 2000.
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24. Keren-Paz, T. Liability regimes, reputation loss, and defensive medicine. Med Law Rev 18, 363, 2010. 25. Keren-Paz, T. Injuries from unforeseeable risks which advance medical knowledge—a restitution-based justification for strict liability. J of European Tort Law. Forthcoming 2014–2015. 26. Hunter v Hanley [1955] SC 200 (Scotland). 27. Kelly, A. Research and the subject: the practice of informed consent. Pol Leg Anthropol Rev 26, 182, 2003. 28. Emanuel, E.J. The Ends of Human Life: Medical Ethics in a Liberal Polity. Cambridge: Harvard University Press, 1991. 29. Roy, D., Dickens, B., and Williams, J. Bioethics in Canada. Scarborough: Prentice Hall, 1994. 30. Anderson, R.E. Billions for defense: the pervasive nature of defensive medicine. Arch Intern Med 159, 2399, 1999. 31. Viscusi, K., and Moore, M.J. Product liability, research and development, and innovation. J Pol Economy 101, 161, 1993. 32. Huber, P.W., and Litan, R.E., eds. The Liability Maze: The Impact of Liability Law on Safety and Innovation. Washington, DC: Brookings Institution, 1991. 33. Tancredi, L., and Nelkin, D. Medical malpractice and its effect on innovation. In: Huber, P.W., and Litan, R.E., eds.
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The Liability Maze: The Impact of Liability Law on Safety and Innovation. Washington, DC: Brookings Institution, 1991, pp. 251–273.
Address correspondence to: Alicia J. El Haj, BSc, MSc, PhD Institute of Science and Technology in Medicine Guy Hilton Research Centre Keele University Thornburrow Drive Hartshill Stoke-on-Trent ST4 7QB United Kingdom E-mail: [email protected] Received: June 3, 2013 Accepted: June 9, 2014 Online Publication Date: July 21, 2014
