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The American Journal of Bioethics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uajb20
Access to Unapproved Medical Interventions in Cases of Catastrophic Illness a
Udo Schuklenk a
Queen's University Published online: 17 Oct 2014.
Click for updates To cite this article: Udo Schuklenk (2014) Access to Unapproved Medical Interventions in Cases of Catastrophic Illness, The American Journal of Bioethics, 14:11, 20-22, DOI: 10.1080/15265161.2014.957626 To link to this article: http://dx.doi.org/10.1080/15265161.2014.957626
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Downloaded by [Florida Atlantic University] at 15:24 26 February 2015
The American Journal of Bioethics
clinical trials (Capdeville et al. 2008; Capri et al. 2010; Stahel et al. 2003). The authors do an impressive job of organizing key features of SAP regulations in different regions (in their Table 1). However, in the United States as of 2009 there are actually three categories of SAPs, not two. These are Single Patient INDs (21CFR312.310) in which Emergency Use INDs are included, Intermediate INDs (21CFR.312.315), and the larger sized Treatment IND/Treatment Protocol (21CFR312.320). The authors also list various design aspects that differ between SAPs but they fail to delineate the obvious potential advantages of some of these features over others (as listed below). One important point this article fails to emphasize is that the majority of patients with incurable, disabling and invariably fatal diseases are going to seek treatment with unapproved therapies (Wasner, Klier, and Borasio 2001). It is not a question of if, but a question of how. Currently most patients are seeking these autonomously, guided by the Internet, where the information ranges from absent to flawed to inaccurate. These patients do not usually share information on what happens to them in such pursuits. Small or individualized SAPs promote shared decision making between a patient and that patient’s clinician, but these lack transparency and reproducibility, place significant demands on the engaged clinician that may not be feasible in today’s medical systems, and again do not systematically gather or share data. We support large centralized SAPs in which a committee of experts transparently creates a suggested protocol and cost structure, and organizes data collection and sharing. The other point these authors miss is that most people want to contribute to research. In our experience this
opportunity would be an added benefit of the type SAPs we describe in the preceding paragraph, rather than an added cost that must be paid to society to justify their existence. &
REFERENCES Bedlack, R. S., D. Pastula, E. Welsh, D. Pulley, and M. Cudkowicz. 2008. Scrutinizing enrollment in ALS clinical trials: room for improvement. Amyotrophic Lateral Sclerosis 9: 257–265. Capdeville, R., T. Krahnke, A. Hatfield, J. M. Ford, I. Van Hoomissen, and I. Gathmann. 2008. Report of an international expanded access program of imatinib in adults with Philadelphia chromosome positive leukemias. Annals of Oncology 19(7): 1320–1326. doi:10.1093/annonc/mdn050 Capri, G., J. Chang, S. C. Chen, et al. 2010. An open-label expanded access study of lapatinib and capecitabine in patients with HER2overexpressing locally advanced or metastatic breast cancer. Annals of Oncology 21(3): 474–480. doi:10.1093/annonc/mdp373 Stahel, R., A. Rossi, L. Petruzelka, et al. 2003. Lessons from the “Iressa” Expanded Access Programme: Gefitinib in special nonsmall-cell lung cancer patient populations. British Journal of Cancer 89(Suppl. 2): S19–S23. Walker, M. J., W. A. Rogers, and V. Entwistle. 2014. Ethical justifications for access to unapproved medical interventions: An argument for (limited) patient obligations. American Journal of Bioethics 14(11): 3–15. Wasner, M., H. Klier, and G. Borasio. 2001. The use of alternative medicine by patients with amyotrophic lateral sclerosis. Journal of the Neurological Sciences 191: 151–154.
Access to Unapproved Medical Interventions in Cases of Catastrophic Illness Udo Schuklenk, Queen’s University A BIT OF HISTORICAL CONTEXT I proposed in the mid to late 1990s that patients suffering from catastrophic illnesses ought to be able to access investigational new drugs outside the clinical trials system, and that we should utilize the information about their experiences with these agents in our evaluation of these investigational agents (Schuklenk 1990). Much of the debate
during the 1980s and 1990s was informed by the horrific experiences of people with HIV and AIDS in our clinical trials systems during the early years of the AIDS pandemic (Nussbaum 1990). Patients died unnecessary deaths in poorly designed clinical trials. Anthony Fauci, head of the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases, conceded reportedly that the clinical trials system routinely asks physicians to
Address correspondence to Udo Schuklenk, Ontario Research Chair in Bioethics and Public Policy, Bader Lane, Watson Hall, Queen’s University, ON, K7L 3N6, Canada. E-mail: [email protected]
20 ajob
November, Volume 14, Number 11, 2014
Downloaded by [Florida Atlantic University] at 15:24 26 February 2015
Access to Unapproved Medical Interventions
sacrifice patient interests to knowledge generation (Hellman and Hellman 1991). This is unsurprising. The very idea that a randomized, double-blind, placebo-controlled clinical trial is ethical if clinical equipoise exists is puzzling. What does it tell us about the knowledge base upon which clinical trials proceed? Saying that I have no reasonable evidence that my experimental agent should proceed to Phase 1 or Phase 2 clinical trials and that it may do just as well as the placebo, is not exactly confidence-inspiring, let alone a plausible justification for a clinical trial involving human participants to proceed. Surely the only rationale for testing an experimental agent in clinical research is that there is some evidence suggesting it might offer therapeutic benefits. If you were a patient whose survival depended on making the right choice on a last-chance treatment option, would you permit yourself to be randomized into a placebo arm or would you go with the however weak evidence in favor of the active agent that led to it being tested in a trial in the first place? HIV-infected patients knew exactly what would happen to them if they ended up getting randomized into placebo arms—they would die. Getting access to the investigational new agent in a trial gave them a shot at receiving a drug that might work against the retrovirus that was killing them and their friends. Catastrophically ill patients knowingly accepted the risks involved in trying investigational new agents, or “experimental drugs,” as these agents were somewhat euphemistically called in those days. Walker and colleagues (Walker, Rogers, and Entwistle 2014) flag rightly in their article concerns that providing unfettered access to experimental agents could well undermine the viability of clinical trials systems. This begs the question of whether public interests ought to trump individual patient survival interests in this instance. We would typically consider such individual sacrifices supererogatory and not part of our obligations as citizens to our fellow community members. That is not to say that we might not have a moral obligation to participate in clinical research, but it is far from clear that we have such a moral obligation when it comes to last-chance treatments in cases of catastrophic illness. I doubt there exists currently a societal consensus anywhere that it is acceptable to compel catastrophically ill patients to participate in placebo controlled, randomized, double-blind trials as the only means of accessing investigational new agents. History taught us another very important lesson here: Coercing dying patients into trial participation turned out to be demonstrably self-defeating. The late Alvin Novick, at the time a member of the FDA’s Anti-Viral Committee, noted: “Patients dropped out of almost all of the trials presented to us at a rate that compromised interpretation of the results. . . . Sometimes they (patients and/or primary care physicians) fake entry data, do considerable detective work to identify whether they are on a placebo or drug, identify the dosage they have received in dose-ranging trials, or otherwise behave actively, by their view of self-interest, rather than as passive subjects.” (Novick 1993, 58–59)
November, Volume 14, Number 11, 2014
Large numbers of patients voted with their feet on what mainstream bioethicists considered at the time ethical trial designs and recruitment conditions. They lied and cheated to get into trials and left trials in such large numbers as to threaten the viability of the AIDS clinical trials system. For this consequentialist reason alone, it seems a moot point to me to debate any longer whether catastrophically ill people have an obligation to participate in placebo-controlled clinical trials as the only means to access investigational new agents. Too many won’t oblige us; hence, alternative access modi were established, importantly also to guarantee the integrity of ongoing clinical research. Whoever decides today to participate in clinical research should do so voluntarily and not as a desperate means to access investigational new agents. INFORMATION SHARING—A NON-ISSUE Since those early days of the AIDS epidemic, bioethicists have continued the conversation on and off about the sharing of patient information. The remaining issues are not quite to do with the question of whether patient information about the experiences patients have with such agents should be passed on to a third party tasked with evaluating these outcomes. It happens in some countries, and—at least to my knowledge—there is no serious argument that has been advanced either by bioethicists or patient advocates that such information must not be shared due to patient privacy and confidentiality issues. Rather, as Walker and colleagues report, many countries do not maximize the utility of the information they would be able to derive from these patients; but that’s a different issue altogether. The reason why I think the patient obligation to share information is a bit of a non-issue has to do with the fact that the relevant information can be sufficiently delinked, such that patient confidentiality and privacy are not violated. What good reasons then could individual patients have for wanting to deny the utilization of the delinked data for research purposes? None that I can think of. Walker and colleagues rightly note that “such data may be comparable to data collected via patient registry databases, or retrospective cohort studies” (12). I doubt a new rationale linking access to experimental agents to a willingness to contribute to knowledge generation is actually necessary. Individual national regulatory agencies should simply make that a fait accompli and ensure that the available data are efficiently evaluated. EQUITABLE ACCESS—THE PERENNIAL ISSUE More problematic remains guaranteeing actual patient access. In Canada, for instance, the government’s special access program leaves it in the hands of pharmaceutical companies to provide compassionate access to potential new drugs that are under investigation in clinical trials. Some companies routinely refuse to do so, without having to provide even so much as an explanation. Arguably, this subverts the very reason for having such special access
ajob 21
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The American Journal of Bioethics
programs in the first place. Companies continue to put undue pressure on patients to join clinical trials they sponsor. This in turn undermines the voluntariness of patient trial participation that led to the problems that I mentioned earlier. Another issue, briefly mentioned by Walker and colleagues, remains a serious practical concern. In Canada, pharmaceutical companies may charge any amount they see fit to catastrophically ill patients wanting to access their investigational agents. Some of these agents may have already shown significant benefits in Phase 2 clinical trials. Patients’ medical insurance, or government schemes designed to cover drug expenses for those unable to afford them otherwise, will—quite rightly—not cover expenses on investigational agents. Walker and colleagues mention our concern that this could lead to a situation where a given society’s poor end up taking their chances in clinical research, while those better off purchase the last-chance agents they desire (Schuklenk and Lowry 2009). The question of equitable access to investigational new agents for clinically eligible patients arises, and it is an important one. There are no immediately obvious answers to the question of who should pay for these agents. The state and insurers would quite rightly object to paying by pointing out that they cannot reasonably be expected to expend scarce resources on agents that are not known to work. Pharmaceutical companies might be compelled to offer these investigational new agents at cost, but these costs could well remain astronomically high, simply because production-level economies of scale have not yet been attained by these companies. It would also take a leap of faith to trust pharmaceutical companies’ claims about the research and development (R&D) cost of medicines (Light and Warburton 2011). They would be typically unwilling to disclose the cost-to-company price of medicines that they plan to sell a few years down the track to us at gigantic markups. We could also compel companies to provide them free of charge to eligible patients. Walker
and colleagues worry that if the pool of potentially eligible patient is too large, companies might be reluctant to investigate relevant drugs. This argument does not strike me as particularly plausible, because it would also suggest that these kinds of R&D-related costs would prevent companies from investigating drugs they could eventually sell to that same large market of patients. The startup costs would be higher but so would be future profits. Still, smaller companies might be unable to finance the provision of investigational new drugs up front under such circumstances. At the time of writing, the issue of affordable, equitable access to investigational new agents needs to be looked at as a matter of urgency in many countries. &
REFERENCES Hellman, S., and D. Hellman. 1991. Of mice but not men: Problems of the randomized clinical trial. New England Journal of Medicine 324: 1585–1589. Light, D. W., and R. Warburton. 2011. Demythologizing the high cost of pharmaceutical research. BioSocieties 6: 34–50. Novick, A. 1993. Reflection on a team of public service with the FDA anti-virals advisory committee. AIDS and Public Policy Journal 8(2): 55–61. Nussbaum, B. 1990. Good intention: How big business and the medical establishment are corrupting the fight against AIDS, Alzheimer’s, cancer and more. New York, NY: Penguin. Schuklenk, U. 1990. Access to experimental drugs in terminal illness: Ethical issues. Binghamton, NY: Pharmaceutical Products Press. Schuklenk, U., and C. Lowry. 2009. Terminal illness and access to Phase 1 experimental agents, surgeries and devices: Reviewing the ethical arguments. British Medical Bulletin 89: 7–22. Walker, M. J., W. A. Rogers, and V. Entwistle. 2014. Ethical justifications for access to unapproved medical interventions: An argument for (limited) patient obligations. American Journal of Bioethics 14(11): 3–15.
Right Answer, Wrong Question: Special Access, Knowledge Generation, and Clinical Trial Legitimacy Christopher Lowry, University of Waterloo I agree with Walker, Rogers, and Entwistle’s (2014) recommendation to make access to an unapproved intervention outside of a clinical trial usually conditional on the
patient’s consent to reasonable data collection and reporting (DCR) for the purpose of knowledge generation. But I do not agree with some key details of their reasons why.
Address correspondence to Christopher Lowry, Department of Philosophy, University of Waterloo, HH Building, Room 365, 200 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada. E-mail: [email protected]
22 ajob
November, Volume 14, Number 11, 2014
The American Journal of Bioethics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uajb20
Access to Unapproved Medical Interventions in Cases of Catastrophic Illness a
Udo Schuklenk a
Queen's University Published online: 17 Oct 2014.
Click for updates To cite this article: Udo Schuklenk (2014) Access to Unapproved Medical Interventions in Cases of Catastrophic Illness, The American Journal of Bioethics, 14:11, 20-22, DOI: 10.1080/15265161.2014.957626 To link to this article: http://dx.doi.org/10.1080/15265161.2014.957626
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Downloaded by [Florida Atlantic University] at 15:24 26 February 2015
The American Journal of Bioethics
clinical trials (Capdeville et al. 2008; Capri et al. 2010; Stahel et al. 2003). The authors do an impressive job of organizing key features of SAP regulations in different regions (in their Table 1). However, in the United States as of 2009 there are actually three categories of SAPs, not two. These are Single Patient INDs (21CFR312.310) in which Emergency Use INDs are included, Intermediate INDs (21CFR.312.315), and the larger sized Treatment IND/Treatment Protocol (21CFR312.320). The authors also list various design aspects that differ between SAPs but they fail to delineate the obvious potential advantages of some of these features over others (as listed below). One important point this article fails to emphasize is that the majority of patients with incurable, disabling and invariably fatal diseases are going to seek treatment with unapproved therapies (Wasner, Klier, and Borasio 2001). It is not a question of if, but a question of how. Currently most patients are seeking these autonomously, guided by the Internet, where the information ranges from absent to flawed to inaccurate. These patients do not usually share information on what happens to them in such pursuits. Small or individualized SAPs promote shared decision making between a patient and that patient’s clinician, but these lack transparency and reproducibility, place significant demands on the engaged clinician that may not be feasible in today’s medical systems, and again do not systematically gather or share data. We support large centralized SAPs in which a committee of experts transparently creates a suggested protocol and cost structure, and organizes data collection and sharing. The other point these authors miss is that most people want to contribute to research. In our experience this
opportunity would be an added benefit of the type SAPs we describe in the preceding paragraph, rather than an added cost that must be paid to society to justify their existence. &
REFERENCES Bedlack, R. S., D. Pastula, E. Welsh, D. Pulley, and M. Cudkowicz. 2008. Scrutinizing enrollment in ALS clinical trials: room for improvement. Amyotrophic Lateral Sclerosis 9: 257–265. Capdeville, R., T. Krahnke, A. Hatfield, J. M. Ford, I. Van Hoomissen, and I. Gathmann. 2008. Report of an international expanded access program of imatinib in adults with Philadelphia chromosome positive leukemias. Annals of Oncology 19(7): 1320–1326. doi:10.1093/annonc/mdn050 Capri, G., J. Chang, S. C. Chen, et al. 2010. An open-label expanded access study of lapatinib and capecitabine in patients with HER2overexpressing locally advanced or metastatic breast cancer. Annals of Oncology 21(3): 474–480. doi:10.1093/annonc/mdp373 Stahel, R., A. Rossi, L. Petruzelka, et al. 2003. Lessons from the “Iressa” Expanded Access Programme: Gefitinib in special nonsmall-cell lung cancer patient populations. British Journal of Cancer 89(Suppl. 2): S19–S23. Walker, M. J., W. A. Rogers, and V. Entwistle. 2014. Ethical justifications for access to unapproved medical interventions: An argument for (limited) patient obligations. American Journal of Bioethics 14(11): 3–15. Wasner, M., H. Klier, and G. Borasio. 2001. The use of alternative medicine by patients with amyotrophic lateral sclerosis. Journal of the Neurological Sciences 191: 151–154.
Access to Unapproved Medical Interventions in Cases of Catastrophic Illness Udo Schuklenk, Queen’s University A BIT OF HISTORICAL CONTEXT I proposed in the mid to late 1990s that patients suffering from catastrophic illnesses ought to be able to access investigational new drugs outside the clinical trials system, and that we should utilize the information about their experiences with these agents in our evaluation of these investigational agents (Schuklenk 1990). Much of the debate
during the 1980s and 1990s was informed by the horrific experiences of people with HIV and AIDS in our clinical trials systems during the early years of the AIDS pandemic (Nussbaum 1990). Patients died unnecessary deaths in poorly designed clinical trials. Anthony Fauci, head of the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases, conceded reportedly that the clinical trials system routinely asks physicians to
Address correspondence to Udo Schuklenk, Ontario Research Chair in Bioethics and Public Policy, Bader Lane, Watson Hall, Queen’s University, ON, K7L 3N6, Canada. E-mail: [email protected]
20 ajob
November, Volume 14, Number 11, 2014
Downloaded by [Florida Atlantic University] at 15:24 26 February 2015
Access to Unapproved Medical Interventions
sacrifice patient interests to knowledge generation (Hellman and Hellman 1991). This is unsurprising. The very idea that a randomized, double-blind, placebo-controlled clinical trial is ethical if clinical equipoise exists is puzzling. What does it tell us about the knowledge base upon which clinical trials proceed? Saying that I have no reasonable evidence that my experimental agent should proceed to Phase 1 or Phase 2 clinical trials and that it may do just as well as the placebo, is not exactly confidence-inspiring, let alone a plausible justification for a clinical trial involving human participants to proceed. Surely the only rationale for testing an experimental agent in clinical research is that there is some evidence suggesting it might offer therapeutic benefits. If you were a patient whose survival depended on making the right choice on a last-chance treatment option, would you permit yourself to be randomized into a placebo arm or would you go with the however weak evidence in favor of the active agent that led to it being tested in a trial in the first place? HIV-infected patients knew exactly what would happen to them if they ended up getting randomized into placebo arms—they would die. Getting access to the investigational new agent in a trial gave them a shot at receiving a drug that might work against the retrovirus that was killing them and their friends. Catastrophically ill patients knowingly accepted the risks involved in trying investigational new agents, or “experimental drugs,” as these agents were somewhat euphemistically called in those days. Walker and colleagues (Walker, Rogers, and Entwistle 2014) flag rightly in their article concerns that providing unfettered access to experimental agents could well undermine the viability of clinical trials systems. This begs the question of whether public interests ought to trump individual patient survival interests in this instance. We would typically consider such individual sacrifices supererogatory and not part of our obligations as citizens to our fellow community members. That is not to say that we might not have a moral obligation to participate in clinical research, but it is far from clear that we have such a moral obligation when it comes to last-chance treatments in cases of catastrophic illness. I doubt there exists currently a societal consensus anywhere that it is acceptable to compel catastrophically ill patients to participate in placebo controlled, randomized, double-blind trials as the only means of accessing investigational new agents. History taught us another very important lesson here: Coercing dying patients into trial participation turned out to be demonstrably self-defeating. The late Alvin Novick, at the time a member of the FDA’s Anti-Viral Committee, noted: “Patients dropped out of almost all of the trials presented to us at a rate that compromised interpretation of the results. . . . Sometimes they (patients and/or primary care physicians) fake entry data, do considerable detective work to identify whether they are on a placebo or drug, identify the dosage they have received in dose-ranging trials, or otherwise behave actively, by their view of self-interest, rather than as passive subjects.” (Novick 1993, 58–59)
November, Volume 14, Number 11, 2014
Large numbers of patients voted with their feet on what mainstream bioethicists considered at the time ethical trial designs and recruitment conditions. They lied and cheated to get into trials and left trials in such large numbers as to threaten the viability of the AIDS clinical trials system. For this consequentialist reason alone, it seems a moot point to me to debate any longer whether catastrophically ill people have an obligation to participate in placebo-controlled clinical trials as the only means to access investigational new agents. Too many won’t oblige us; hence, alternative access modi were established, importantly also to guarantee the integrity of ongoing clinical research. Whoever decides today to participate in clinical research should do so voluntarily and not as a desperate means to access investigational new agents. INFORMATION SHARING—A NON-ISSUE Since those early days of the AIDS epidemic, bioethicists have continued the conversation on and off about the sharing of patient information. The remaining issues are not quite to do with the question of whether patient information about the experiences patients have with such agents should be passed on to a third party tasked with evaluating these outcomes. It happens in some countries, and—at least to my knowledge—there is no serious argument that has been advanced either by bioethicists or patient advocates that such information must not be shared due to patient privacy and confidentiality issues. Rather, as Walker and colleagues report, many countries do not maximize the utility of the information they would be able to derive from these patients; but that’s a different issue altogether. The reason why I think the patient obligation to share information is a bit of a non-issue has to do with the fact that the relevant information can be sufficiently delinked, such that patient confidentiality and privacy are not violated. What good reasons then could individual patients have for wanting to deny the utilization of the delinked data for research purposes? None that I can think of. Walker and colleagues rightly note that “such data may be comparable to data collected via patient registry databases, or retrospective cohort studies” (12). I doubt a new rationale linking access to experimental agents to a willingness to contribute to knowledge generation is actually necessary. Individual national regulatory agencies should simply make that a fait accompli and ensure that the available data are efficiently evaluated. EQUITABLE ACCESS—THE PERENNIAL ISSUE More problematic remains guaranteeing actual patient access. In Canada, for instance, the government’s special access program leaves it in the hands of pharmaceutical companies to provide compassionate access to potential new drugs that are under investigation in clinical trials. Some companies routinely refuse to do so, without having to provide even so much as an explanation. Arguably, this subverts the very reason for having such special access
ajob 21
Downloaded by [Florida Atlantic University] at 15:24 26 February 2015
The American Journal of Bioethics
programs in the first place. Companies continue to put undue pressure on patients to join clinical trials they sponsor. This in turn undermines the voluntariness of patient trial participation that led to the problems that I mentioned earlier. Another issue, briefly mentioned by Walker and colleagues, remains a serious practical concern. In Canada, pharmaceutical companies may charge any amount they see fit to catastrophically ill patients wanting to access their investigational agents. Some of these agents may have already shown significant benefits in Phase 2 clinical trials. Patients’ medical insurance, or government schemes designed to cover drug expenses for those unable to afford them otherwise, will—quite rightly—not cover expenses on investigational agents. Walker and colleagues mention our concern that this could lead to a situation where a given society’s poor end up taking their chances in clinical research, while those better off purchase the last-chance agents they desire (Schuklenk and Lowry 2009). The question of equitable access to investigational new agents for clinically eligible patients arises, and it is an important one. There are no immediately obvious answers to the question of who should pay for these agents. The state and insurers would quite rightly object to paying by pointing out that they cannot reasonably be expected to expend scarce resources on agents that are not known to work. Pharmaceutical companies might be compelled to offer these investigational new agents at cost, but these costs could well remain astronomically high, simply because production-level economies of scale have not yet been attained by these companies. It would also take a leap of faith to trust pharmaceutical companies’ claims about the research and development (R&D) cost of medicines (Light and Warburton 2011). They would be typically unwilling to disclose the cost-to-company price of medicines that they plan to sell a few years down the track to us at gigantic markups. We could also compel companies to provide them free of charge to eligible patients. Walker
and colleagues worry that if the pool of potentially eligible patient is too large, companies might be reluctant to investigate relevant drugs. This argument does not strike me as particularly plausible, because it would also suggest that these kinds of R&D-related costs would prevent companies from investigating drugs they could eventually sell to that same large market of patients. The startup costs would be higher but so would be future profits. Still, smaller companies might be unable to finance the provision of investigational new drugs up front under such circumstances. At the time of writing, the issue of affordable, equitable access to investigational new agents needs to be looked at as a matter of urgency in many countries. &
REFERENCES Hellman, S., and D. Hellman. 1991. Of mice but not men: Problems of the randomized clinical trial. New England Journal of Medicine 324: 1585–1589. Light, D. W., and R. Warburton. 2011. Demythologizing the high cost of pharmaceutical research. BioSocieties 6: 34–50. Novick, A. 1993. Reflection on a team of public service with the FDA anti-virals advisory committee. AIDS and Public Policy Journal 8(2): 55–61. Nussbaum, B. 1990. Good intention: How big business and the medical establishment are corrupting the fight against AIDS, Alzheimer’s, cancer and more. New York, NY: Penguin. Schuklenk, U. 1990. Access to experimental drugs in terminal illness: Ethical issues. Binghamton, NY: Pharmaceutical Products Press. Schuklenk, U., and C. Lowry. 2009. Terminal illness and access to Phase 1 experimental agents, surgeries and devices: Reviewing the ethical arguments. British Medical Bulletin 89: 7–22. Walker, M. J., W. A. Rogers, and V. Entwistle. 2014. Ethical justifications for access to unapproved medical interventions: An argument for (limited) patient obligations. American Journal of Bioethics 14(11): 3–15.
Right Answer, Wrong Question: Special Access, Knowledge Generation, and Clinical Trial Legitimacy Christopher Lowry, University of Waterloo I agree with Walker, Rogers, and Entwistle’s (2014) recommendation to make access to an unapproved intervention outside of a clinical trial usually conditional on the
patient’s consent to reasonable data collection and reporting (DCR) for the purpose of knowledge generation. But I do not agree with some key details of their reasons why.
Address correspondence to Christopher Lowry, Department of Philosophy, University of Waterloo, HH Building, Room 365, 200 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada. E-mail: [email protected]
22 ajob
November, Volume 14, Number 11, 2014
