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To the Editor: Emily Largent and Steven Pearson, in their article “Which Orphans Will Find a Home? The Rule of Rescue in Resource Allocation for Rare Diseases” (Jan-Feb 2012) venture into difficult terrain—the allocation of scarce medical resources—at a time when medical needs outstrip these resources and cost control is being sought. But their focus on rare diseases requires comment. Rare, or “orphan,” diseases are easy targets. The very label “rare disease” invites the view that such a disease is peripheral and unimportant to the health care system. This is truly unfortunate. Not only does it seem to justify abandoning millions of people, but it can also undermine the integrity of the entire research enterprise, reducing the chances of finding successful treatments for all diseases, common and rare alike.
Under the federal Orphan Drug Act of 1983, “rare disease” is defined as any disease that affects fewer than 200,000 people in the United States. There are about seven thousand such diseases. In all, rare diseases affect nearly thirty million Americans, two-thirds of them children. These diseases have few or no treatments (under four hundred rare diseases have treatments approved by the Food and Drug Administration on the American market), and few research efforts are dedicated to finding more.
Have individuals and families dealing with rare diseases resorted to “rule-of-rescue” tactics, going public with painful personal stories to advance their place in line and deflect medical resources to their needs? A few have, of course. But the vast majority of individuals and families facing rare diseases are invisible to the wider society. Their communities are small and isolated, and their days are spent dealing with their own medical challenges or those of their children. As a result, most rare diseases are unknown to the general public. In fact, when it comes to garnering media notice, celebrities battling common diseases—like cancer, diabetes, heart disease, and Alzheimer disease—collect far more attention. It is simply not true that those with rare diseases have mounted an orchestrated appeal for “unrestrained rescue,” as Largent and Pearson claim.
The authors invoke the concept of “opportunity costs”: the loss to many who will do without if resources are used to help the few with rare diseases. When considering opportunity costs, one must factor in the cost of research dedicated to the discovery of treatments and cures. The investment in research on common diseases is huge, and its cost is huge. By contrast, the current investment in research on rare diseases is very small. Further marginalizing this effort (because effective-treatment outcomes may be considered too costly to use) would drive that limited investment still lower. This would discourage young scientists from doing rare disease research, no matter how potentially fruitful it might be, since it is impossible to build a scientific career without funding.
Reducing research on rare diseases would also harm the broad scientific enterprise that supports modern medicine. Because they often have a singular genetic basis, rare diseases present unique scientific opportunities for understanding gene action without the confounding factors that characterize common disorders (factors such as contributions from multiple genes, environmental influences, diet, and smoking and other lifestyle choices). The study of rare diseases has already provided fundamental understandings of genetic systems, biochemical pathways, and DNA-repair mechanisms that have helped elucidate the basis of and improve treatments for common diseases. The blockbuster drugs Botox and Viagra were originally developed to treat benign essential blepharospasm and pulmonary hypertension, two rare disorders.
To overcome the existing research-funding shortfall, many patient groups try to raise money themselves through garage sales, car washes, and bake sales. They may need several years to raise enough to fund even a single research effort associated with a particular rare disease. At a recent meeting of the Medical Advisory Committee of the National Organization for Rare Disorders, we struggled to decide which of two excellent research grant submissions should receive the available modest funding. Even with all its hard work, the patient group providing the funding had raised only enough money for one seed grant.
Those with rare diseases are not asking for “preference” when it comes to allocation of resources, as Largent and Pearson claim, but only a fair shake. The tax dollars used for governmental research programs come out of their pockets, too, and society has an ethical duty not to punish minorities for small numbers. Not only they, but the wider community, benefit from continued support of research, since such research is essential to the health of the overall medical-science enterprise.
More attention should be directed to reducing the high cost of all medications and treatments. We should encourage the many drug companies waiting to enter the marketplace with generic alternatives. Today's expensive rare disease drugs will become more affordable when competition from generics drives prices down. Since people with rare diseases are geographically dispersed, no single government or insurance company is overwhelmed by the cost of orphan drugs. In fact, insurers admit that they could save more money by shaving a half-penny off the price of a popular cholesterol drug than by slicing a few thousand dollars off the price of an orphan drug. The cost of orphan drug treatments to society is far less than that of acne treatments.
As Largent and Pearson indicate, there are other ways to cut medical costs—ways that call for sacrifice from all of us. That we will have to make tough calls about allocation of health care resources is certain. But those dealing with rare diseases shouldn't have to be first in line to justify their needs and defend their treatments.
Virginia Polytechnic Institute and State University and the National Organization for Rare Disorders
To the Editor: In “Reasonable Disagreement about Identified vs. Statistical Victims” (Jan-Feb 2012), Norman Daniels finds an element of moral reasonableness in the bias for identified over statistical victims and concludes that it may properly influence health policy. In the same issue, Emily Largent and Steven Pearson show how, through the rule of rescue, the same bias is involved in our willingness to support expensive treatments for rare diseases; they conclude that the bias is unsupportable, since it cannot be acted on consistently.
Daniels ends up finding moral relevance in one element behind identified victim bias: concentration of risk. Reasonable people can prefer saving someone who needs all of a given resource, for example, over saving one person through the equally effective elimination of one-in-five risks for five. Many no doubt have such a preference. The real moral test for anyone who supports the bias past the point of merely breaking productivity “ties,” though, is this: Are you willing, in doing this, to reduce your own likelihood of having your life prolonged? For that is the result of society vesting identified victims with greater moral weight; people are as likely to lose from low investment in measures that save not-yet-identified lives as they are from low investment in saving identified lives. Maybe they are willing to make this sacrifice. But if they are not, their support for the identified victim bias is hardly reasonable. The public process of accountability for reasonableness that Daniels urges should put them to the test.
In describing consequentialist arguments for the bias, Daniels notes the interesting empirical finding that “educating people about the bias… reduces charitable donations to the identified victims without leading to increased giving to statistical victims.” Wisely, I think, Daniels does not rest his case for the reasonableness of the bias on this fact (he moves on to concentration of risk). In any case, the relevance of this claim to an assessment of identified victim bias is questionable. If we abandon the bias, we do not have to leave our investment in saving statistical lives at the low level that resulted from it. We will abandon it precisely because we have come to imagine saved statistical lives as eventually being the lives of real, identifiable individuals. That will raise our willingness to save statistical lives, not necessarily reduce our willingness to save identified ones.
Such heightened imagination is not as unrealistic as people presume when they dismiss as pie-in-the-sky the prospect that society could equally value identified and statistical lives. In clinical prevention, for example, the chances that preventive action will save the life of a person before us are low, but people do not necessarily fail to “see” the individual who benefits from such low-odds measures. The flood of objections against the arguably well-reasoned recommendation of the U.S. Preventive Services Task Force that not all women between ages forty and fifty routinely have annual mammograms shows this. When these women are screened annually, approximately two thousand women must have mammograms to extend one life. Many objected that that one is a real individual who will lose her life. Never mind that the real number may be one out of six thousand, or what other parts of the Task Force's reasoning its critics generally ignored. People's ability to imagine a real individual life lost despite its location in a sea of dispersed risk represents an advance in moral thinking. Under the right circumstances, people really can see statistical lives as real people lost or saved—which, in fact, they are! So the bias against statistical victims may not be all that durable.
Largent and Pearson may be pointing in this same direction when they write, “if our sympathy is engaged by several identifiable individuals suffering and dying, should we not be moved even more by the suffering and death of numerous unidentified individuals?” They properly lament the opportunity costs of living by rule of rescue, but they miss the primary moral rationale for the Orphan Drug Act. They argue it is not unfair to deny one hemophilia patient treatment costing $300,000 a year if treatment costing the same amount is not provided to victims of more common diseases. This is a real fairness issue. But the source of the perception of unfairness when rare disease victims are left without treatment lies elsewhere: not in cost-bearing principles, but in the chances of a cure being found.
The fact is that without some compensating legislation, rare diseases are much less likely to gain the attention of drug developers. Small numbers mean smaller profits—too small to support the higher per-beneficiary cost of research and development. Rare disease victims thus become “drug orphans.” Isn't it an arbitrary stroke of bad luck for such a victim that he or she happens to be caught by a rare instead of a common disease? That is the unfairness driving the incentives the Orphan Drug Act creates for rare disease drug development. Such drugs will inevitably be more expensive, on average, per patient. Encouraging orphan drug development is pointless, though, if no one is willing to pay that higher expense.
Pacific Lutheran University (emeritus)
To the Editor: Emily Largent and Steven Pearson attempt to identify ethical arguments to justify a special reimbursement status for some—though not all—orphan drugs. In doing so, they review the troubled past and current state of research and development into and reimbursement of orphan drugs, as well as criticizing the rule of rescue as a credible foundation for special status. Despite their criticism, they state that their aim is to “find a way to respect the strong moral impulse captured by the rule of rescue while taming it to achieve a sustainable coverage policy for drugs and other therapies for small numbers of patients.” Inherent in this aim is a value judgment that population health care allocation decisions should weigh individuals’ health differently based upon the prevalence of their disease.
In addition to identifiability, which they dismiss as an ethical basis for special status, Largent and Pearson consider three key concepts that may be useful mechanisms for “respecting the moral impulse of the rule of rescue”: endangered lives, opportunity costs, and justifiable rescues. The authors understand “endangered lives” to mean death or substantial role impairment due to disease, which allows them to posit that treatments for this kind of disease may deserve special status in reimbursement decisions. They place a constraint on this special status through their concept of justifiable rescue—that is, treatments that offer “a meaningful opportunity to save lives or to maintain or restore capacities central to functioning in society.” For orphan drugs to receive special status for reimbursement, meeting the endangered lives and justifiable rescue criteria are necessary conditions. They are not, however, sufficient for coverage.
Largent and Pearson recognize that the fragmented nature of the U.S. health care system makes identifying the opportunity cost associated with covering an expensive orphan technology difficult, but that this difficulty does not mean the opportunity cost does not exist. They argue that unless decision-makers can communicate to stakeholders how a treatment's benefits to patients with rare diseases will outweigh or justify the opportunity cost borne by others, stakeholders are unlikely to want to cover it. Transparency is the mechanism for achieving balance between opportunity costs and appropriate consideration of the needs of people with rare diseases.
In 2004, the U.K. National Institute for Health and Clinical Excellence, through its Citizens Council, made recommendations about orphan drugs similar to the endangered lives and opportunity cost criteria. These recommendations hold that the need must be significant and the treatment must be effective; merely stabilizing disease is not enough to justify paying a premium for orphan drugs. The third, perhaps sufficient, condition endorses the principle of “accountability for reasonableness” proposed by Norman Daniels and James Sabin in their 2002 book, Setting Limits Fairly: Can We Learn to Share Medical Resources? These principles are generally accepted as desirable for all health care resource allocation decisions, and Largent and Pearson do not say why applying them in the context of orphan drugs is substantively different.
I have argued previously that a special status for orphan drugs will have to rest on their defining characteristic—rarity. Either rarity has a value on its own, or it substantially alters the value attached to some other criteria, such as severity of ill health or magnitude of health gain. If neither of these conditions holds, then there is no ethical justification for orphan drugs having a special status in reimbursement processes. To date, research examining whether a condition's prevalence impacts, directly or indirectly, on the value attached to health gain from treatments has found that it does not (A.S. Desser et al., “Societal Views on Orphan Drugs: A Cross-Sectional Survey of Norwegians Aged 40 to 67,” BMJ 341 (2010): c4715).
In the absence of evidence to support a special value for rarity, looking to justify a special status for such treatments is not appropriate. If we value effective treatments for severe conditions equally, regardless of how many have the condition, then the likelihood of the treatment being covered should be equal.
Health care resource allocation decisions are population health decisions; funding one person's health care means not funding someone else's. In a socially funded system such as the U.K. National Health System, this is easy to see. In insurance-based systems like the one in the United States, the people whose health care is not funded are those who cannot afford the higher insurance premiums that result when an expensive technology is covered. Largent and Pearson are concerned that ethical population health care resource allocation conflicts with the value imperatives behind individual moral choices. The reality is that the value frameworks should be different because individuals bear the opportunity cost of private choices, whereas others bear the opportunity cost of population coverage decisions. In such circumstances, the value framework used should be consistent across all decisions, not tailored to the identifiable beneficiaries of specific decisions.
To the Editor: I have become convinced that clinical medicine and bioethics exist in two separate worlds. The prolonged discussion about expensive rescues by Largent, Pearson, and Daniels, and the difficulty they have fitting them into their model worlds, strengthens this perception.
Most consumers of health care services (a.k.a. patients) seek access to medical care systems because they want to be rescued from the effects of some malady; in fact, the mission of health care is to rescue individuals from the suffering caused by disease. In addition, I would argue that the need to provide “rescue” from suffering is a behavior either imprinted genetically or almost universally learned, and part of what makes us human. For example, if an infant on an airplane has an earblock (a very painful condition caused by inability to equalize pressure in the ears) and is screaming, not only will the infant suffer, but almost everyone within hearing distance will, too, because of their inability to “rescue” the infant.
If “rescue” is the purpose of health care, even with the understanding that all rescues are time limited (life is a fatal disease), then failure to rescue is a critical systems failure because it results in increased morbidity and mortality. When bioethicists plan not to rescue someone because the condition she has is too expensive, they are accepting a preplanned, critical system failure. Health care consumers have been told by some of the same people that they have a right to health care and so promised rescue. Upon finding out they have a condition that is not covered due to a bureaucrat's arbitrary decision, they will not only suffer from the untreated condition, but also be able to claim a breach of the social contract between the health care system and themselves. This unhappiness is likely to lead to protests, attempts to maneuver the system, outright fraud, or revolution. In addition to the affected consumer, those who witness the failure to rescue will also be distressed. Finding out the “universal health care system” isn't universal doesn't go over well with consumers.
University of Texas M.D. Anderson Cancer Center
To the Editor: One of the most profound insights in the last century of political science was Mancur Olson's observation that government policies and spending will be biased in favor of concentrated interests at the expense of the wider public. Industrial polluters, for example, will have a greater incentive to devote resources to lobbying against pollution regulation than will the many people who experience the small adverse effects of pollution. Olson's observation is relevant to discussions of identifiable victims and the rule of rescue because, as Largent and Pearson point out in their beautifully crafted essay, the interests of those with orphan diseases are concentrated, whereas the costs of those treatments tend to be dispersed across the population through infinitesimally higher taxes or insurance premiums.
Concentrated victims tend to get disproportionate attention not only because they have a greater incentive to lobby politicians, but also for psychological reasons. As Norman Daniels points out in his superb article in the same issue, the concentration of victims accentuates and may even underlie a phenomenon first identified by Thomas Schelling and eventually dubbed the “identifiable victim effect”: our tendency to provide more aid to known individuals or small groups in need. Both factors—the concentration of interests noted by Olson and our tendency to respond more sympathetically to identified victims—can distort resource allocation, shifting resources away from diffuse, statistical victims and toward concentrated, identified ones.
Where both papers fall short, in my view, is in their treatment of the opportunity costs of dealing with such identifiable victims. Both assume, explicitly or implicitly, that there is a fixed pool of resources assigned to health care, so that using more resources in one domain of health will take away from other domains. Largent and Pearson, for example, point to “the tension that can arise in health care between doing the most good possible with scarce health care resources and the desire to assist identifiable individuals regardless of cost” (emphasis added). But health care is not a zero-sum situation; it has no fixed budget, so increasing funding in one area will not necessarily lead to decreased funding in another. If the identifiable victim effect led to disproportionate spending on identified victims, we could conclude that statistical victims were getting short shrift. But since health care spending is not zero sum, then we may actually be spending too little on both identifiable and statistical victims. The identifiable victim effect would then reduce underspending on identified victims, which rectifies one wrong, even if it would be better also to devote more resources to statistical victims. Then the policy prescription would not be to reduce spending on identified victims, but to increase it on statistical ones.
The idea that the United States is spending too little money on health care might seem absurd, but it's not. The United States does not spend more than other countries because we value identified victims too highly, but because we overspend on high-cost, low-value medical services—a point emphasized in the recent report by Consumers Union and by nine medical groups identifying tests and procedures routinely provided but conferring little or no benefit. Moreover, these services are provided largely for the reason that Olson described so well: the concentrated economic interests of health care providers trump the diffuse interests of health care users.
Spending as much as we do on identified victims is going to seem unattractive if we assume—as the authors of these papers do—that the money is going to come at the expense of measures aimed at statistical lives, like preventing disease. Suppose, instead, that the tradeoff was between spending on identified victims or on high-cost, low-value health services. The option of cutting spending on identified victims so we can preserve or increase services of little benefit seems a whole lot less attractive than cutting spending on identified victims to increase spending on prevention.
I agree with the authors of both papers that the United States needs to establish policies to determine what we should spend money on based on underlying values rather than on the economic interests of providers. As Largent and Pearson argue, we ought to spend to treat orphan diseases, but only when the treatments are demonstrably beneficial. The same principle should apply to all treatments. The United States used to have an agency—the Agency for Healthcare Policy and Research—that provided expert, independent guidance on the value of medical services, but it was gutted by Congress after back surgeons lobbied when it recommended against surgery as preferred treatment for lower back pain. Regardless of how resources are allocated among identified and statistical victims, the real problem in the U.S. health care system is the influence of the concentrated economic interests of medical providers.
Carnegie Mellon University