Allergic to Generics

Allergic to GenericsTroyen A. Brennan, MD, and Thomas H. Lee, MD

A 69-year-old woman with several medical problems believes thatshe is allergic to generic medications. She frequently conflicts withher long-time primary care physician, who, as required by thepatient’s insurance coverage, refuses to prescribe brand-namedrugs when generic alternatives are available. This conflict inten-sifies to a crisis when the patient develops life-threatening prob-lems and still will not take prescribed generic medications. Thepresentation of this real case is accompanied by a discussion of

the ethical dilemmas of the patient’s physician, who must weighthe interests of a patient who clings to beliefs that the physicianthinks are unfounded against the interests of a just rationingprogram and the broader population it serves.

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A 69-year-old woman with diabetes mellitus and supraven-tricular tachycardia believes that she is allergic to generic med-ications. Her primary care physician has cared for her for 12years. Her medical problems include arthritis, diabetes melli-tus, hypertension, dyspepsia, and depression. She frequentlycomes to the office or the emergency department with symptomsthat do not have an apparent physiologic basis. Over the lastdecade, she has undergone a wide range of diagnostic proce-dures that have not shown clinically significant abnormalities.A psychiatric consultation 4 years ago led to the conclusion thatshe had somatization disorder. On the advice of the psychia-trist, the primary care physician sees the patient frequently inthe office and tries to minimize diagnostic testing and newmedications.

Three years ago, the patient received a generic preparationof glyburide and developed a rash typical of a drug allergy. Thepatient concluded that she was allergic to generic medicationsand refused to fill prescriptions for any generic drug. She couldnot be convinced that allergy to all generic medications, butnot to their brand-name counterparts, was impossible. Sherefused referral to an allergist, asserting that “I know mybody.” Her physician continued to insist on trials of genericmedications when appropriate for her problems and refused toprescribe brand-name drugs when generic alternatives wereavailable, as mandated by her insurance program, the stateMedicaid program. She occasionally would agree to try a ge-neric medication. However, she developed diffuse itchingwithin a few minutes of taking the medication and wouldthen discard the rest of the prescribed medication.

The patient’s refusal to take generic drugs became a con-stant focus of her relationship with the primary physician,which had been generally warm and effective. Discussions ofthis issue added several minutes to most visits. Since theirconflict about treatment with generic drugs was unresolved,her physician suggested that she might prefer to seek anotherphysician, but she declined. Her physician compromised:When she needed medication for problems that were not po-tentially serious, he would insist on prescribing a generic med-ication and leave it to the patient to decide whether to fill theprescription. She generally left the office with the prescriptionbut did not take the medication. When she had a seriousproblem, the physician would prescribe a brand-name drug,

even when an effective generic alternative was available. Forexample, when he treated her for hypertension, he prescribedan angiotensin-receptor blocker, for which no generic alterna-tives exist, instead of a generic angiotensin-converting enzymeinhibitor. The patient asked the physician to write a letter toMedicaid indicating that she was allergic to generic medica-tions. He refused.

This patient’s fears about using generic medicationshave led to constant conflict between her and her primarycare physician. Most physicians have “problem patients” or“difficult patients.” Literature on ethical and practical is-sues with such patients and management strategies fordealing with them has increased. Difficult patients are of-ten defined as those who engender a negative reaction fromtheir physicians (1–3). Estimated prevalence of difficult pa-tients in a primary care panel ranges from 15% to 30% (4,5). Many of these patients have underlying psychologicaldisease; personality disorders are especially common (5).

While most of this literature focuses on the patient,the “problem patient” does not exist in a vacuum. As thiscase shows, the adjective “difficult” actually characterizesthe relationship between these patients and their physiciansas they address conflict, including clinical issues that arisebecause of the socioeconomic environment of medicalpractice. The physician–patient relationship is a complexinterplay of personalities. In this case, the physician’s ratherzealous support for policies aimed at reducing inefficiencyin health care contribute to the conflict in their relation-ship.

The conflict might not exist except for the state Med-icaid program’s limitations on its pharmacy benefit. TheMedicaid program in Massachusetts does not cover brand-name drugs when generic counterparts are available unlessphysicians explain in writing why the brand-name drugsare medically necessary. Most states’ Medicaid programsare struggling to meet their budgets today, partly becausethe Medicaid programs’ average annual rate of growth forprescription drugs costs was 19.7% from 1998 to 2002.Forty-eight states report that pharmacy costs were a topreason for Medicaid expenditure growth (6). In this case,the state is therefore taking the perfectly rational step of

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not covering brand-name drugs when equivalent genericdrugs are available.

One year ago, the patient was hospitalized through theemergency department because of dyspnea and a sensation ofchest pressure. She was in supraventricular tachycardia, whichresponded to a �-blocker. She did not have evidence of myo-cardial injury, was discharged symptom-free, and received ge-neric atenolol after a 1-day stay. When she filled her dischargeprescription for atenolol, she discovered that her physician hadprescribed a generic medication. She did not take the atenolol.Her primary care physician warned her that she was riskingher life, and she insisted that he prescribe a brand-name�-blocker. He refused, pointing out that the low-cost genericdrug was equivalent to the brand-name drug.

At this point in the case, the ethical issues have be-come clear. The physician is in a classic conflict of interestsituation. A conflict of interest occurs when the will toachieve certain secondary objectives inappropriately influ-ences progress toward a primary objective (6). In this case,the primary objective is the well-being of the patient. Thesecondary interest is the cost-effective generic drug policyof the Medicaid program.

Twenty years ago, few would have joined the debateabout what to do: Most ethicists would have instructed thephysician to ignore the requirements of the insurer andsimply treat the patient with the more expensive brand-name medication. According to this traditional under-standing of medical ethics, the physician’s altruistic com-mitment to the patient would trump the interests of thestate. As Pellegrino (7) persuasively stated: “Physicians arehealers first, and in this role, financial incentives and com-modification of health care must be ignored.”

However, medical ethics has slowly evolved to a dif-ferent view of such issues. Wikler (8) neatly formulatedwhat many others agree is an important evolution in med-ical ethics (8). In the first stage, ethical behavior was merelya matter of adherence to codes of professional ethics. In thesecond stage, which marked the birth of bioethics in the1970s, the focus was the physician–patient relationship.Ethical behavior is rooted in a personal commitment to analtruistic model of this relationship. In the third stage, bio-ethicists placed the physician–patient relationship into thelarger structure of health care in society.

Once medical ethics recognizes the social context ofdisease and care, it must consider issues of justice, includ-ing the distribution of scarce health care goods. As healthcare costs have increased, the gap between health care forthe wealthy and health care for the poor has widened.Medical ethics in the United States has increasingly recog-nized this disparity as an urgent ethical issue and has re-sponded by incorporating the just distribution of resourcesinto its framework for ethical behavior. Of course, the no-tion of scarcity and rationing as a response is not new. TheHealth Care and Medical Priorities Commission of Swe-den’s Ministry of Health and Social Affairs has noted that

rationing is “inevitable; rationing has always been part ofhealth care. . . [A]ny rationing scheme must [have] threecore principles, all human beings are equally valuable, so-ciety must pay special attentions to the needs of the weak-est and most vulnerable, and cost efficiency, all else beingequal must prevail” (9). Today, growing consensus dealswith scarcity, and developing reasonable methods of ra-tioning is an integral part of medical ethics.

If one accepts the important role of justice in a frame-work for ethical behavior in health care, the ethical analysisof the present case resolves itself into answering 2 ques-tions: First, is the rationing mechanism just? Second, is thephysician taking the right actions to resolve the conflict?On the first question, Emanuel (10) has suggested that atleast 3 principles must be considered in allocating healthcare resources justly: Improving health should be the pri-mary goal, patients should be well-informed, and patientsshould have the opportunity to consent.

Applying the first principle is perhaps most critical toanalyzing this case. Our struggle to apply it emphasizes thedifficulty that ethicists and physicians face in balancing thetwin imperatives of an altruistic physician–patient relation-ship and just distribution of resources. In this case, thephysician would best serve the patient’s health by provid-ing the brand-name �-blocker. However, if we consistentlyallow patient choice to trump scientifically based, reason-ably cost-effective treatment strategies, Medicaid fundingwill be inadequate to meet the program’s responsibilities. Afiscally compromised Medicaid program might have todeny care for other patients, and the overall health of so-ciety would be ill-served. So, the physician in this case is, inessence, balancing the patient’s request for a brand-namedrug with the need to conserve resources so that the Med-icaid program can serve as many legally entitled patients aspossible. The stakes in this case are lower than they wouldbe if the Medicaid program had to deny bone marrowtransplantation for a child with a controversial indication,but the nature of the ethical conflict is the same. Medicalethics has acknowledged that the conflict exists, which is animportant advance. However, a principle that leads to easyresolution of individual cases has not been found.

A “generics-only” guideline seems reasonable from acost-effectiveness perspective. Use of generic drugs, whichin most circumstances are exactly like their much morecostly brand-name counterparts, is a noncontroversialmethod of conserving resources. However, we must decideon a case-by-case basis whether rationing by substituting aless costly alternative is just. If the scientific rationale issound, the rationing mechanism is probably just (11). Bur-ton and colleagues (12) analyzed the ethics of pharmaceu-tical benefit management programs. They argued that alimited formulary is a reasonable rationing mechanism andthat prohibiting prescription of a brand-name medicationis appropriate when a generic equivalent is available. Weconclude that insisting that a patient accept a generic drugis a just method to allocate resources. The patient’s physi-

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cian was acting fairly when he used this principle in hisethical framework for dealing with the patient.

The fairness of the allocation principle in this programdoes not imply that all pharmaceutical benefit manage-ment programs are just. Other situations may introduceissues that change the way we ask about the appropriate-ness of limiting access to pharmaceuticals. For example, ifthe insurer was a for-profit corporation, the physicianswere capitated, or physicians received direct financial re-ward if they adopted a generics-only prescribing policy,physicians’ conflict of interest would be substantiallysharper, and we might conclude that they were acting un-ethically because the secondary considerations involvedpersonal gain. Increasing the intensity or immediacy of theincentive for physicians to reduce costs (for example,through stronger financial incentives) would intensify theconflict (13). On the other hand, effective negotiationswith pharmaceutical companies might reduce the pro-gram’s expenses for brand-name drugs and decrease theneed for this conflict.

In this case, we have a public insurer and, at least as faras we know, no financial pressure on the physician. AMedicaid program, unlike a private insurer, has a relativelyclear mandate when it tries to resolve the trade-off betweenincreasing resources for an individual patient and increas-ing the number of patients who can be eligible for cover-age. Simply put, insisting that the patient use a genericdrug in this context improves health care. It is a “win” forsociety and a “no lose” for the patient, at least if she takesthe drug.

We believe that improving health care is paramount.In an earlier era of medical ethics, many ethicists mighthave argued that the principle of beneficence, doing goodfor patients, might lead a physician to prescribe brand-name drugs for this patient. In the present era, fewer wouldadopt this viewpoint. We do not think that the principle ofbeneficence entails absolute deferral to the patient’s wishes.The supporting statement from the Medicine as a Profes-sion Managed Care Ethics Working Group in this issue(14) gives carefully nuanced advice in dealing with insur-ance companies and managed care.

We need to consider Emanuel’s other 2 principles ofjust allocation (10). First, the requirement for the patientto consent to treatment takes a different form when she isthe beneficiary of a public program. While the patientclearly controls the choice of a therapeutic intervention,such as whether or not to have surgery or take medication,she cannot really choose medication when the public in-surer adheres to its formulary. Wealthier individuals mightopt for a different insurer, which allows greater choiceabout medications. Most public program recipients do nothave this option.

The patient in this case study probably has nowhereelse to turn for health insurance, and, as an insurer of lastresort, Medicaid cannot provide the patient with muchchoice. Choice is limited in public programs. Rather than

assert the patient’s right to choose between equivalentforms of the same treatment as a safeguard to ensure fair-ness, we must closely scrutinize the scientific rationale ofthe cost-effectiveness measures that the public programuses.

Continuing our analysis by using Emanuel’s principleof patient consent (10), we note that the physician seemsto have been honest and direct in his discussions with thepatient. Although the case report is not completely clear onthis point, we are reasonably sure that the physician hastold the patient that he is insisting on generic atenololbecause the Medicaid program itself insists on it. Hedoesn’t have a personal financial incentive. When physi-cians have to “bluff or puff” about their financial incen-tives, the physician–patient relationship changes for theworse, often irretrievably. These awkward conversationsbetween uncomfortable physician and suspicious patienthave brought important ethical questions about certainmanaged care techniques to public attention (15). If we aregoing to ration, we must honestly explain our decisionmaking to our patients and respond when they voice theirconcerns. Presumably, the physician in this case gave anaccurate explanation, although research by Pearson andHyams (16) has suggested that physicians are not alwayscompletely honest about efforts to cut costs. They oftensimply ask the patient to trust them (16).

In our analysis of this case, we should ask whether thisparticular Medicaid program allowed physicians to petitionfor a waiver from prescribing rules. If it did, the physiciancould advocate the patient’s position and still play withinthe rules. Should he do so? He would have to repress hisown convictions about just allocation of resources, but per-haps the opportunity to petition for a waiver is the pro-gram’s way of affirming that the patient’s need shouldcome first in the uncommon instance of an irreconcilableconflict. However, programs usually grant these waiversonly when the approved medication has a clear contrain-dication. As indicated in the Medicine as a ProfessionManaged Care Ethics Working Group statement (14), wecould not sanction the physician if he lied to get a waiverfor this patient (although many patients and some physi-cians might sanction it).

Finally, with regard to the conflict of interest itself, wenote that the physician has addressed the patient’s needs ina graded fashion in the past. The physician was willing toprescribe brand-name medications when the problem wasclinically significant, insisting on generic drugs only whenthe problem was relatively clinically insignificant. Essen-tially the physician weighed the best interests of the patientagainst the interests of the just rationing program. We be-lieve that many would find this compromise acceptableand that it is a good example of bringing principles ofjustice and health care rationing to the bedside. Most well-designed Medicaid pharmaceutical benefit programs alsorecognize that “problem” patients may require compromiseand have appeal programs that allow substitution of non-

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generic medications in some circumstances. At this point,medical ethics still seems to give primacy to the physician’sduty to advocate for the patient but, in contrast with thepast, now requires the physician to try hard to allocateresources justly.

One week later, the patient had a heart rate of 160beats/min at her adult day care program. The nurse called herphysician, who directed the nurse to tell the patient to take heratenolol. The patient refused. The nurse suggested that thepatient go to another physician, but the patient said, “I wanthim to write the prescription. If he won’t and I die, it will beon his head.” When the nurse continued to encourage her toswitch physicians, the patient said, “I’ve known him for somany years, and he knows me so well. I don’t want to start allover with someone new.”

At this point, the conflicting forces are challenging thephysician–patient relationship. On one side are the pa-tient’s beliefs about generic drugs. On the other side is thephysician’s commitment to practice according to guide-lines that ensure just allocation of resources. With the on-set of supraventricular tachycardia in an elderly, diabetic,hypertensive woman, this conflict has intensified to a crisis.A generic medication normally produces no decrement inquality, unless the patient will not take it. However, be-cause this patient adamantly refuses to use generic medica-tions, her physician’s adherence to Medicaid’s policy nowthreatens her health.

As medical ethics has evolved in the last part of the20th century, notions of distributive justice have modifiedthe doctrine of patient autonomy. Still, patient autonomyis, rightly, a potent ethical driver of daily practice. Accord-ing to Burton and colleagues (12), autonomy issues weighstrongly when the ethics of pharmaceutical benefit man-agement are reviewed. We normally attempt to respect pa-tient’s decision making about their use of health care re-sources.

Autonomy has limits. We expect patients to be re-sponsible participants in their health care. As Daniels andSabin (17) pointed out, a reasonably just health care systemdepends on health care organizations, insurers, physicians,and patients all being accountable for their actions. Pa-tients must use health care resources rationally. If they donot, we cannot simply accede to irrational choices. But, attimes, we must be prepared to compromise principles ofequity with the needs of an individual patient.

Therefore, the physician must reconsider his stance.Although the guideline prohibiting generic drugs is quiterational, the high risk that the patient will harm herself,albeit unintentionally, by not taking generic medicationsmust tip the physician in the direction of prescribing abrand-name medication. In the end, he bows to the pa-tient’s iron will, perhaps thinking that the Medicaid pro-gram would be harmed if all patients behaved like thiswoman but realizing that most patients behave more ratio-nally than she.

When the nurse called the physician back to report thatthe patient would not take any medication unless he prescribedit, he relented and prescribed a brand-name, long-acting�-blocker.

This case study demonstrates the extraordinary intri-cacies of the physician–patient relationship. Everyone whohas been or has treated a patient knows that this relation-ship has nuances. The interdependence, respect, concern,and affection in the physician–patient relationship con-found the principles that form the basis of a market econ-omy. Here, the patient has been battling with the physicianwho will not give her brand-name medications, yet sheremains extraordinarily committed to that physician be-cause she believes that he has her welfare at heart. From thephysician’s viewpoint, the duty to provide care tempers allthe difficulties and frustrations of dealing with an irrationalpatient. Most relationships between 2 citizens in the liberalstate could not tolerate such a sharp division of belief overa fundamental issue. But, the strong ties of the therapeuticalliance, with its acceptance of human frailty, allow thephysician to continue to care for the patient and the pa-tient to accept his care.

In this situation, the physician makes the appropriatechoice. The conflict among the patient’s fundamental rightto choose her treatment, her worsening health, and thephysician’s commitment to practice in a certain way be-came too strong. Perhaps the physician became a utilitarianat the end. He may have realized that the patient’s wors-ening condition shifted the balance of benefit and harm (asaveraged across all participants affected by this episode,including himself, the patient, and other Medicaid pa-tients) to net benefit for prescribing a brand-name drug. Inany case, he heeded his commitment to the patient andprescribed the more expensive medication.

We believe that this physician will continue to try toinstruct and educate his patient, perhaps to little avail. Hewill continue to insist on accountable and reasonable be-havior by the patient, but he will relent when necessary. Hemay guide the patient toward psychiatric help.

This case illustrates the increasingly prominent role ofdistributive justice as a principle of medical ethics. We nowexpect physicians to balance their obligation to an individ-ual patient with their obligations to all who may needmedical care. The accompanying Medicine as a ProfessionManaged Care Ethics Working Group statement (14) il-lustrates the extent to which this thinking has become partof the mainstream of medical practice. This dual obligationdoes create challenges, which try our patience and test ourpatients’ loyalty to us. Ultimately, the physician and thepatient usually resolve the conflict and move on together.

From Brigham and Women’s Hospital, Partners Community Health-care, Harvard Medical School, and Harvard School of Public Health,Boston, Massachusetts.

Potential Financial Conflicts of Interest: None disclosed.

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Requests for Single Reprints: Troyen A. Brennan, MD, Brigham andWomen’s Hospital, 75 Francis Street, Boston, MA 02115; e-mail,[email protected].

Current author addresses are available at www.annals.org.

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8. Wikler D. Presidential address: bioethics and social responsibility. Bioethics.1997;11:185-92. [PMID: 11654772]

9. Health Care and Medical Priorities Commission. No Easy Choices: The Dif-ficult Priorities of Health Care. Swedish Government Official Report. Stock-holm, Sweden: Ministry of Health and Social Affairs; 1993.

10. Emanuel EJ. Justice and managed care. Four principles for the just allocationof health care resources. Hastings Cent Rep. 2000;30:8-16. [PMID: 10862365]

11. Emanuel EJ, Goldman L. Protecting patient welfare in managed care: sixsafeguards. J Health Polit Policy Law. 1998;23:635-59. [PMID: 9718517]

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13. Pearson SD, Sabin JE, Emanuel EJ. Ethical guidelines for physician com-pensation based on capitation. N Engl J Med. 1998;339:689-93. [PMID:9725929]

14. Povar GJ, Blumen H, Daniel J, Daub S, Evans E, Holm RP, et al. Ethics inpractice: managed care and the changing health care environment. Medicine as aProfession Managed Care Ethics Working Group statement. Ann Intern Med.2004;141:131-5.

15. Illingworth P. Bluffing, puffing and spinning in managed-care organizations.J Med Philos. 2000;25:62-76. [PMID: 10732876]

16. Pearson SD, Hyams T. Talking about money: how primary care physiciansrespond to a patient’s question about financial incentives. J Gen Intern Med.2002;17:75-8. [PMID: 11903778]

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Current Author Addresses: Dr. Brennan: Brigham and Women’s Hos-pital, 75 Francis Street, Boston, MA 02115.

Dr. Lee: Partners Community Healthcare, Inc., Prudential Tower, 11thFloor, 800 Boylston Street, Boston, MA 02199.

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Allergic to Generics