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Subtracting injury from insult: ethical issues in the use of pharmaceutical implants.

Subtracting Injury from Insult: Ethical Issues in the Use of Pharmaceutical Implants

Ten years ago, psychosurgery, "gene surgery," and surgical sterilization received considerable attention in bioethics. These interventions provided riveting examples of the kinds of questions that the young field took as its domain: questions about the ethical boundaries of biomedicine's power to modify bodies and minds. The focus of the field has since shifted. Soon, however, the concerns of the last decade may be raised again, from a quite different corner of biomedicine. Advances in biomedical engineering and pharmaceutical chemistry are converging to produce devices that can be implanted in the body to deliver controlled doses of rdugs automatically for months at a time. [1] These implants could be used to produce the effects of psychosurgery, surgical sterilizations, and even some genetic surgeries, without their irrevocable invasions of bodily integrity. For contemporary pharmaceutical engineers, and for clinicians of the 1990s, the question is how well the earlier exploration of biomedicine's moral boundaries provides guidance in this new pharmacologic terrain.

In one respect, the discussion of the ethical issues raised by the surgeries does provide important precedents for the ethics of drug implantation: its analyses do map the relevant moral ground. However, the language of those analyses, while nicely crafted for their contexts, could seriously mislead efforts to evaluate the use of drug implants. Its dominant metaphors--trespass, unjust punishment, and irretractable offense--can be misread to imply that the clinical virtues of implantation--noninvasiveness, efficiency, and reversibility--allow this practice to escape the moral pitfalls encountered by the surgeries. To follow the lead of the earlier discussion successfully requires a critical rereading of its metaphors that can distinguish between their clinical and moral meanings.

Implantable Drug Delivery Systems

In the next two decades we may expect a revolution in drug therapy. In addition to the new hormones, enzymes, and vaccines that the biotechnology industry is producing, new techniques for drug delivery are being introduced. One idea that has received considerable attention from academic and industrial researchers is the development of implantable devices designed to release a drug into the body in a controlled manner. A well known example is the mechanical insulin pump carried by some diabetics. [2] Subcutaneous reservoirs, which deliver drugs passively into the blood stream, have been under development since the late 1960s. [3] "NORPLANT" (R), the implantable contraceptive device developed by The Population Council, is a more recent example. This small plastic rod infused with a contraceptive steroid is inserted subcutaneously under local anesthetic. The device is physically unobtrusive and can automatically release preset contraceptive doses for five years after implantation. [4] Current research is also aimed at developing self-regulated implants capable of interacting with their environment to meet the body's fluctuating pharmacologic needs. [5]

The reversibility and longevity of an implant depends on its design. In principle, implants can be designed to release drugs over virtually any duration, although most current devices have life spans measured in months rather than years. Some systems, like NORPLANT, are designed to remain intact throughout the release process and must be removed surgically when exhausted. Others are designed to degrade into nontoxic by-products as the drug is released. Because they often lose their mechanical integrity during erosion, degradable devices may not be removable once implanted. Thus, while they may be more convenient than nondegradable devices, they may preclude other treatment choices for considerable periods of time.

In part, implantation is attractive because the traditional routes for drug delivery--ingestion or injection--are not well suited to the administration of new, genetically engineered biologicals. Such drugs are usually proteins and would be digested if taken orally. They also usually require regular administration, burdening patients with the inconvenience and discomfort of living with a prolonged course of injections. Implantable devices, by providing for the measured, subcutaneous release of a drug, are designed to obviate these problems.

Implantation holds advantages for other classes of drugs as well. Because they can be implanted near their target organs, less drug is required to achieve the same effect as oral or intravenous administration. "Organ targeting" has also been shown to avoid many of the side effects of oral administration by reducing the drug's dispersal and absorption in other parts of the body. [6]

Finally, developing improved pharmaceutical implants is attractive for more prosaic reasons. The process of developing, screening, clinically testing, and obtaining regulatory approval for a new drug often requires decades. Yet patent protection is relatively short (seventeen years), and must often overlap with several stages of the process. Drug companies are finding it less lucrative to develop new drugs than to seek new delivery methods for existing ones.

All these considerations may drastically change our view of what it means to be "taking drugs" for a medical problem. The combination of implantation's efficiency (in terms of enhanced drug efficacy, reduced side effects, greater convenience, and better compliance), with its relative noninvasiveness and reversibility give the technology distinct clinical advantages. There is a danger, though, that these virtues could distract us from other problems that could arise in prescribing this technology.

The Double-Edged Virtues of

Implantation Technology

As a novel therapeutic tool, any new implantable drug delivery device will present the same ethical questions that attend other clinical innovations: Its introduction will be marked by uncertainty about safety and efficacy, and its use will entail predictable risks as well as benefits. Drug implantation, in other words, is a double-edged technology in the usual sense of having both virtues and vices as a clinical tool. But these are not the issues that we address here. Drug implantation may also face ethical questions precisely when it virtues recommend its use. To the extent that they cause us to neglect those questions, implantation's virtues themselves may be double-edged. Ironically, their distracting potential is probably greatest whee these questions are most pressing, because of the way our moral metaphors exacerbate it. Under their influence, implantation's clinical virtues appear to condone its use in cases whee any intervention would be morally problematic.

Noninvasiveness

One of the primary reasons contraceptive implants are attractive is that they provide the long-term prophylaxis of surgical sterilization without requiring a major medical intervention. But consider the following scenario:

The parents of an eighteen-year-old girl with Down syndrome come to their physician for help. Their daughter is sexually mature, and has an IQ of sixty-five. She is able to get about on her own and attends a special school each day. Her parents had hoped to place her in an adult group home when she completed school, but fear that she may well become pregnant and that this will be a very upsetting experience for her. They have tried oral contraceptives, which the girl refuses to take without a daily struggle, and they do not wish to subject her to the risks of an IUD. They feel that sterilization through tubal ligation is the only answer. However, they are relieved to learn about the existence of a biologically implantable device like NORPLANT that will have the same effect, and request it from their physician. [7]

Ethical debate on surgical sterilization for retarded adolescents usually contrasts the psychological burden of pregnancy and the potential psychosocial benefits of sexual activity with the surgery's harm to the patient's reproductive capacity, the lack of her consent to the procedure, and the foreclosure of her future reproductive options. [8] The issue turns on which course seems better to promote the patient's autonomy: to exercise, on her behalf, her right to sterilization, or to defend, since she cannot, the privacy of her reproductive choices. [9]

All of these considerations would also be present in a decision to fit the patient with a long-term contraceptive implant. The patient would be rendered infertile without her consent, and in a way that she would be powerless to change for an extended period. The problem of determining her competency to make reproductive choices and raise children remains, as well as the prospect of infringing unjustifiably on a very important sphere of personal decisionmaking.

However, the implant will not sterilize the patient permanently, as tubal ligation would. Moreover, implantation entails neither the dramatic invasion of bodily integrity of surgery nor the recurrent struggle of administering oral contraceptives. It is a minor procedure, performed in the doctor's office and then forgotten. Do these clinical advantages help ameliorate the physician's ethical problem?

Those concerned about surgical sterilization of the retarded ofen cite the bodily injury of the procedure in the same breath with its insult to the patient's autonomy. For example, one cautious critic of sterilization argues that:

A just cause is required because sterilization in the absence of consent constitutes a significant invasion of the body and a rather massive intrusion into the sphere of reproductive privacy. [10]

Here, the "trespass" metaphors of "invasion" and "intrusion" provide useful but complementary descriptions of both the physical harms and moral wrongs involved in involuntary sterilization.

Nevertheless, "trespass" metaphors do tend to focus on the consequences of surgery for (structural) bodily integrity rather than for (functional) reproductive capacity. The prospect of minimally invasive implantable contraceptive devices forces us to ask which of these harms is really of central concern. If the decisive ethical issue is how best to promote the subject's reproductive autonomy, how relevant is the fact that involuntary implantation can compromise reproductive function without a "significant invasion of the body"?

The "bodily invasion" of surgery provides a graphic symbol of trespass, but it is the intervention's functional effects that intrude furthest into the subject's reproductive privacy. Of course, invasive surgery is riskier than subcutaneous implantation: the noninvasiveness of the implant gives it a genuine clinical advantage, which counts ethically in its favor. However, to the extent that the noninvasiveness of the implantable contraceptive is viewed as the decisive ethical consideration in cases like this, the language of the surgical sterilization debate will have misled our moral reflection. In this debate, appeals to bodily integrity play a primarily rhetorical role; they are designed to invoke the metaphors of trespass that underscore the importance of the reproductive function at stake.

Efficiency

The increased efficacy and convenience of pharmaceutical implants can also distract us from important ethical issues. Consider the use of biosynthetic growth hormone to increase the height of short, but genetically normal children:

An eight-year-old boy is referred to an endocrinologist for evaluation of extreme short stature. After a normal infancy, the patient's growth slowed and by his third birthday his height was below the tenth percentile of children his age. His general health has been excellent and psychological adjustment is said to be good. His mother is fifty-nine inches tall and his father sixty-four. The patient's height is forty-six inches, but there are no other abnormal physical findings. Determinations of serum growth hormones are normal. His parents ask about biosynthetic growth hormone, but are discouraged by the prospect of a long series of intramuscular injections. However, it is now possible to deliver the hormone subcutaneously through an implant. Should the physician provide the treatment? [11]

Like the early discussions of "gene surgery," the current debate over using biosynthetic growth hormone to treat endocrinologically normal children intertwines conceptual and clinical problems. Conceptually, the issue is whether short stature should be counted as a pathological condition, appropriately treated by medicine, or whether the problems that very short people encounter are better blamed on a social environment geared to taller frames. [12] Clinically, psychologists point out that, beyond uncertainties about the physical risks of giving extra growth hormone to a normal child, there is a real danger that a prolonged series of intramuscular injections will precipitate the very psychological problems it is intended to prevent. If the patient has not yet experienced his height as a problem, an extended course of medical treatment will surely suggest to him that it poses one, at least in the eyes of his parents and physicians. [13]

In current discussions of growth hormone treatment, conceptual worries about whether the therapy is ever indicated in endocrinologically normal children fade quickly into the background of clinical concerns about the iatrogenic risks of undermining the therapy's prophylactic goals. For example, the major professional statement on the issue concludes that:

Replacement of growth hormone in growth hormone deficient children is the only established indication for growth hormone therapy. Treatment of all non-growth hormone deficient patients must be considered experimental....As the investigational use of growth hormone is expanded, researchers and clinicians should bear in mind that handicaps resulting from short stature often have psychological origins. Therefore, even for experimental studies, GH therapy should be restricted to children in whom it is judged that emotional status can be significantly improved....In selecting patients for GH trials, the wise physician might adhere to the old adage, "If it ain't broke, don't fix it." [14]

Here the conceptual question of whether very short bodies are "broken" is left open, and the question of the appropriate limits of medical intervention is addressed at the clinical level, where our grip on what is broken and what is not is somewhat firmer.

Certainly, a pharmaceutical implant would substantially diminish the iatrogenic risks of treating the child's stature with growth hormone. Using the implant will be painless and will not require repeated visits to the doctor. It is also likely to be more effective, decreasing the duration of the treatment. The child would have his stature enhanced with much less trauma than his orthodonture is likely to involve, and with comparably fewer psychological sequelae.

However, the endocrinologist is still left with the ethical challenge of decide whether the contemplated treatment is indicated in the first place. In what sense is this patient handicapped? If the patient's stature is considered a handicap simply due to prejudice against short people, combating the prejudice seems a more appropriate response than treating the child.

It is not surprising that the immediate iatrogenic risks of growth hormone therapy should play a prominent role in ethical discussion of the practice, it provides a graphic reminder at the clinical level of the basic problem the therapy faces. In trying to help individual victims of our social environment we risk reinforcing the sociocultural roots of their problems. The elective use of growth hormone to increase the height of short normal children by those who can afford the treatment only serves to link height even more closely to other socially valuable traits like health and wealth. [15] Since there will always be a shortest third percentile, this treatment seems likely to exacerbate the general bias against short stature. During implantation would break the link between this social danger and its psychological analog at the clinical level. By reducing the "tell-tale" iatrogenic risks of the treatment for the individual patient, drug implants would distract us from confronting the fundamental question growth hormone therapy for short stature raises, and make it easier to run the larger social risk.

Reversibility

It is easy to see how invasiveness and iatrogenesis play important symbolic roles in ethical debates over involuntary sterilization and growth hormone treatment. But is the clinical irreversibility of either intervention merely a rhetorically useful side issue as well? The reversibility of implantation seems to speak most directly to the ethical issues in these cases, because it provides a way to proceed in the face of moral uncertainty. For example, consider the case for using implants as an alternative to psychosurgery, an intervention that, if misused, combines both the surgical trespass of tubal ligation and the iatrogenic injustice of growth hormone treatment:

A long-term impatient at a mental institution with a history of paranoia and violent behavior consistently refuses to comply with a regimen of anti-psychotic drugs. Electroencephalographic examination of the patient shows brain activity compatible with temporal lobe epilepsy. Because of this finding, the institution's medical staff discusses psychosurgery as an alternative to the patient's forced medication. However, since the patient's medications, once administered, do seem effective in controlling his behavior, they are hesitant to proceed. As a third option, a consulting pharmacologist suggests that an implantable drug delivery system be used to supply the patient's regimen of anti-psychotic medication automatically for months at a time.

The ethics of psychosurgical intervention oscillates around two relates issues: distinguishing the cure of behavioral pathology from unjustified behavior control, and determining a psychiatric patient's authority to refuse (or consent to) this kind of treatment. [16] Neither of these issues is peculiar to psychosurgery and a decision to use a pharmaceutical implant raises exactly the same questions about how best to promote and protect this patient' interests. However, commentators usually argue that psychosurgery is a paradigm for ethical conflicts in behavior control techniques because of its invasiveness, destructiveness, and irreversibility:

Psychosurgery is perhaps the most dramatic of all medically based individual therapies for mental and behavioral deviance. It goes directly to the physical seat of experience, and makes irreversible destructive lesions. Because of its dramatic quality, psychosurgery focuses with great intensity the fundamental problem of all behavior control: by what values should behavior be controlled? [17]

What is special about psychosurgery, then, is the way it metaphorically underscores its own moral dangers: Not only does it offend the patient's integrity, but its insult is one that can never be retracted. Psychosurgery's irreversibility, like its invasiveness, neatly dramatizes the seriousness of the moral hazards it shares with growth hormone therapy and surgical sterilization: the misuse of medical expertise and the violation of the patient's personal autonomy. The question raised by the prospect of a pharmaceutical implant is whether the permanence of psychosurgery has any other moral significance, against which the implant's reversibility measures favorably.

Clearly, there are clinical situations in which the implant's reversibility would make it the intervention of choice. For example, lucid patients might be given the opportunity to commit themselves to a "Ulysses contract," with the option of renegotiating at the end of each cycle. [18] However, in our case, the staff must still face the central issues of whether the goal of the intervention is therapeutic or coercive, and how to respond when the patient refuses it. If the staff's intent is coercive or the patient's refusal valid, the fact that the implant's behavioral effects are reversible will not undo the wrong that forced implantation would represent. Could we justify denying individuals the right to vote by pointing out that they will get another chance in the next election?

Of course, the implant could be proposed simply to test the validity of the patient's refusal. If it were used to enhance our confidence in the patient's capacity for self-determination and to allow him to make an authoritative decision about further treatment, the moral importance of its reversibility would increase. In fact, if the goal of such a test is to return control to the patient, the preference should be for the most readily reversible intervention that would work: for example, a course of traditionally administered medication. Here, the convenience of the implant may recommend its use (as it did in the growth hormone case), but its relative longevity and irreversibility actually militate against it.

More important, just why does the moral significance of reversibility increase when implantation is used to resolve our uncertainty about the patient's capacity? In this situation, the implant's reversibility opens the possibility of making amends for the moral insult of its imposition on the patient. But the significance of this is only that it allows us to apologize for imposing the test, not that it renders apologies unnecessary. The implant's reversibility does not allow us to avoid inflicting the insult in the first place, any more than it speaks to the question of whether behavior control is the appropriate prescription for this patient's problems. Once again, it would be a mistake to let the prominence of the "irreversibilityc rhetoric in the psychosurgery debate suggest that the reversibility of pharmaceutical implants allows us to avoid all the serious ethical concerns of psychosurgery.

Moral and Clinical Meanings

The noninvasiveness, increased efficiency, and reversibility of pharmaceutical implants will make implantation technology the preferred approach to drug delivery in an increasing number of situations, and rightly so: they are genuine virtues. Implantable devices can accomplish the goals of surgical sterilization, growth hormone treatment, and psychosurgery without the invasiveness, iatrogenic risk, or irreversibility that serve as graphic reminders of the moral issues these latter interventions raise. But having subtracted the injuries of those interventions from their insults, drug implantation can still leave clinicians facing the most serious moral problems of the surgeries: the conflicts between visions of personal autonomy and difficulties in distinguishing the appropriate therapeutic uses of medical knowledge from its abuses on behalf of social prejudices and priorities.

To remain sensitive to these problems, it is important to be able to distinguish the moral and the clinical meanings of the metaphors that give implantation's virtues their appearance of moral force. It is natural that biomedicine should focus on the clinical interpretations of "trepass," "unjust punishment," and "irrevocable insult," and seek therapeutic strategies, like drug implantation, that can address them. But this search risks distracting us from the moral dangers the metaphors warn against. To the extent that drug implantation will be contemplated in cases like those examined above, these hazards still exist in the moral terrain this technology must cross. The charts of this terrain provided by its pioneers will be invaluable in that crossing, but only if we translate their signs and symbols correctly.

References

[1] See A.C. Tanquary and R.E. Lacey, eds., Controlled Release of Biologically Active Agents (New York: Plenum Press, 1974); Perry J. Blackshear, "Implantable Drug Delivery Systems," Scientific American 241:6 (December 1979), 66-73; Joseph Kost and Robert Langer, "Controlled Release of Bioactive Agents," Trends in Biotechnology 2 (1984), 47-51.

[2] Michael Sefton, "Implantable Pumps," CRC Critical Reviews in Biomedical Engineering 14 (1987), 201-40.

[3] Robert A. Ratcheson and Ayub K. Ommaya, "Experience with the Subcutaneous Cerebrospinal-Fluid Reservoir: Preliminary Report of 60 Cases," New England Journal of Medicine 279:19 (November 7, 1968), 1025-31.

[4] Irving Civin, "Clinical Effects of NORPLANT Subdermal Implants for Contraception," Advances in Human Fertility and Reproductive Endocrinology 2 (1982), 89-116.

[5] Seo Y. Jeong et al., "Self-Regulating Insulin Delivery Systems," Journal of Controlled Release 2 (1985), 143-52.

[6] B.B. Pharris et al., "Progestasert: A Uterine Therapeutic System for Long Term Contraception," Fertility and Sterility 25:11 (November 1974), 915-21.

[7] We are indebted to Adele Hoffman and James Morrissey for this case, which we have adapted for our purposes.

[8] Ruth Macklin and Willard Gaylin, eds., Mental Retardation and Sterilization: A Problem of Competency and Paternalism (New York: Plenum Press, 1981).

[9] Daniel Wikler, "Paternalism and the Mildly Retarded," Philosophy and Public Affairs 8 (1979), 915-21.

[10] LeRoy Walters, "Sterilizing the Retarded Child," Hastings Center Report 6:2 (April 1976), 13-15.

[11] This case is adapted from Case 3 in Louis Underwood and Barry Sherman, "Controversies in the Treatment of Short Stature," in Synthetic Growth Hormone in Clinical Practice, ed. Barry Sherman and Louis Underwood (New York: Marcel Dekker, Inc., 1987), 145-191.

[12] Martin Benjamin, James Muyskens, and Patricia Saenger, "Short Children, Anxious Parents: Is Growth Hormone the Answer?" Hastings Center Report 14:2 (April 1984), 5-9.

[13] Cf. Brian Stabler, "Comments," in Underwood and Sherman, "Controversies," at 172-78.

[14] Ad Hoc Committee on Growth Hormone Usage, "Growth Hormone in the Treatment of Children with Short Stature," Pediatrics 72:6 (December 1983), 891-94.

[15] Martin Benjamin, "Sharing Uncertainty: The Case of Biosynthetic Growth Hormone," in Biomedical Ethics Reviews 1985, ed. James M. Humber and Robert F. Alexander (Clifton, NJ: Humana Press, 1985), 109-129.

[16] Ruth Macklin, Man, Mind and Morality: The Ethics of Behavior Control (Englewood Cliffs, NJ: Prentice-Hall, 1982), 15-18.

[17] Robert Neville, "Psychosurgery," in The Encyclopedia of Bioethics, ed. Warren Reich (New York: Macmillan, 1978), 1387.

[18] See also Rebecca Dresser, "Bound to Treatment: The Ulysses Contract," Hastings Center Report 14:3 (June 1984), 13-17.

Eric Juengst is assistant professor of humanities (philosophy) at the College of Medicine, Pennsylvania State University. Ronald Siegel is assistant professor of pharmacy at the University of California, San Francisco.
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Author:Juengst, Eric; Siegel, Ronald
Publication:The Hastings Center Report
Date:Dec 1, 1988
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