Editor’s Note: The following consultation report is based on a real clinical dilemma that led to a request for an ethics consultation. Some details have been changed to preserve patient privacy. The goal of this column is to address ethical dilemmas faced by patients, families and healthcare professionals, offering careful analysis and recommendations that are consistent with biblical standards. The format and length are intended to simulate an actual consultation report that might appear in a clinical record and are not intended to be an exhaustive discussion of the issues raised.
Column editor: Robert D. Orr, MD, CM, Consultant in Clinical Ethics, CBHD.
Is it ethically permissible to stop the off-label use[1] of an expensive drug in this child with Gaucher’s disease since it is likely not working and she may be suffering because of its continued use?
Jessica is a 2 ½ year old girl who was evaluated at 7 months of age for failure to thrive and enlargement of her liver and spleen. She was found to have Gaucher’s disease, a genetic (recessive) lipid storage disease, the manifestations of which are due to the absence of an enzyme. She was seen in consultation at a Pediatric Research Center. It was not known which of three types of this disease she has. She was begun 19 months ago on a 6-month trial of a replacement enzyme which is approved for and effective in preventing the manifestations of the disease in two of the three types of Gaucher’s disease. The family was unable to return to the Research Center for the 6-month follow-up visit. The treatment has been continued, and, at her parents’ urging, her dosage has been increased to higher than normal. She has had frequent long hospital admissions (infections and seizures) and she has developed problems suggestive of progressive disease (including respiratory failure; she has been on a ventilator at home for several months) strongly suggesting to her physicians that she has the more severe type of this disease that does not benefit from enzyme replacement.
On the other hand, her liver and spleen have decreased in size, she has survived longer than the average for patients with the more severe type (typically, death before age two), her parents point out that she has grown some, and they are convinced that she shows signs of neurologic development while at home. However, during her frequent hospitalizations, she has shown minimal awareness; at best she smiles, responds to her parents, and follows simple commands. She is currently at home and receives total parental nutrition, home mechanical ventilation, a morphine drip (for bone pain) and the intravenous enzyme every 14 days.
Her overall therapy is very expensive (to date > $1.4 million); the enzyme alone costs several thousand dollars per month. Both Dr. Burgess, Jessica’s primary pediatrician, and the research consultant believe the enzyme is no longer medically indicated. The medical director of her managed care organization is denying payment for the enzyme until he can be convinced there is a valid medical indication to continue; she is now 9 days late in getting her injection. In addition, Dr. Burgess is concerned that progressive disease and invasive treatments are causing her sufficient suffering that continued treatment may be inappropriate if it is merely postponing her inevitable death.
Jessica’s parents are her caregivers at home, and they have declined assistance from home nursing. They have no other children. Her mother no longer works outside the home so is able to be home full time, and her father has reduced his work as an accountant to part time in order to help. Friends from their church are supportive and help the family in many ways.
This case involves a child with a chronic and ultimately fatal disease who is being treated with an expensive medication. Her physicians believe the treatment is not effective, is merely prolonging her suffering, and thus is no longer appropriate. Her parents believe it is working and request that it be continued.
The first issue involves communication of information between the physician and family. Many times miscommunication occurs because we treat medicine as a science, as if outcomes can be known with logical certainty. This is not always true. Medicine can be messy. It is frequently difficult in the early treatment of a disease to predict severity or impact on the child’s life. In our ‘scientifically minded’ physician role, we try to place the patient in categories to give the patient’s family information to prepare for the future. In doing so, however, we make subconscious assumptions which lead the families to misunderstand the goals of therapy and their limitations. There may also be miscommunication as to what the therapy actually is. Is it research, or treatment?
In this case, the child was not placed on a clinical trial but was started on enzyme replacement therapy which had shown promise in ongoing clinical research studies. It is not clear in this case whether the indications and risks of therapy, as well as the endpoints of therapy, were clearly discussed with her family. After nineteen months, she is still receiving the medicine which was started as a six month trial, now at a higher dose than is used in research trials.
The second dilemma involves the withdrawal of inappropriate or marginally effective therapy. By necessity, this is a physician driven decision, though it depends on information from patient or family.
Jessica’s parents almost certainly order their lives and decisions based on what they feel is best for their child’s quality of life. Although the primary care physician is concerned about suffering on the part of the child, the final decision about the child’s quality of life rests with the parents. It is ethically permissible to override such parental quality of life decisions only when those decisions are clearly detrimental to the child. It is in this mode that we interact as physicians: our duty is to assess Jessica’s therapies (not just her enzyme replacement) as to their medical appropriateness. In reference to replacement enzyme therapy, the primary benefit of halting neurologic degeneration has not been effective, though she has probably had some secondary benefit from the therapy. This benefit will not influence her overall prognosis or well-being.
Both of these dilemmas highlight the difficulty for physicians to properly communicate what is known and unknown. Clear discussions regarding the indications for therapy and the end point for those therapies might have prevented the present dilemma. Practically speaking, a formal discussion regarding prognosis, reasons for starting or discontinuing therapy, and alternatives if therapy does not work should be initiated at the beginning of treatment. Periodic interim discussion should be planned throughout the course of treatment so that the parents can have realistic goals and expectations. These discussions should also include an acknowledgement of what we don’t know: the effectiveness of off-label use of the enzyme, how the disease might progress without the therapy or even how the therapy would be paid for if not covered by insurance.
Whether or not this ideal of discussion was followed in this case, we must deal with the problem at hand. It is never too late to have an honest, transparent conversation with the family, including openness about how misperceptions and miscommunications may have clouded the issue. The physician should specifically take responsibility for failing to outline the treatment goals. He or she can then ask the family to reconsider their position. This reconsideration will only be effective, however, if the professional caregivers are also willing to reconsider their position. They should reconsider the parents’ claim that neurologic improvement has occurred with the therapy, using objective measures as much as possible. They should also reassess the amount of suffering the child is subjected to in treatment. This may make it easier for the parents to reach a compromise position about the goals of treatment and overall care of their child.
Four months later, Dr. Burgess reported that the patient was still receiving the enzyme, paid for by the insurance company. After more discussion, her mother had become more realistic about the outcome. In addition, her professional caregivers were more convinced that she had actually improved (videos of her motor function at home showed considerably better function than they had observed at the hospital). There was no further discussion about discontinuing the enzyme at that time.
Nine months after the consultation, Jessica developed uncontrollable seizures. Her parents consented to both a Do Not Resuscitate order and to withdrawal of the ventilator. She died in about 35 minutes.
[1] Use of a drug for a condition for which it has not been approved by the FDA.
This case study, used by permission, originally appeared in Ethics & Medicine: An International Journal of Bioethics Volume 23 Issue 3, Fall 2007.
