- Email: [email protected]
Ethical Issues and Paclitaxel (TAXOL®) Administration
Ethical Issues and Paclitaxel (T AXQL®) Administration Judith Kehs Much Although less concrete than the practical issues involved In the administration of paclltaxel. the ethical concerns are nonetheless important. Anything that elicits the broad range of emotions shown by individuals seeking. receiving. or administering paclltaxel is bound to raise ethical concerns. General ethical principles can be applied to the "paclltaxel experience," It Is helpful to look at ethical principles within the context of pressure exerted on caregivers to provide paclltaxel. These pressures include high media profile of the drug. reported drug activity. and environmental Issues. The high media profile has led to tremendous public demand. which has in turn influenced access and referral issues. When a new. promising drug is released. It is important for those nurses who have worked with the drug In clinical trials to participate in the transfer of technical information to the community. This must include Information designed to sensitize caregivers to the variety of Issues and concerns raised in relation to the drug that they provide. Copyright © 1993 by W.B. SlIunders Compllny
T
HE WORDS hope, rage, desperation, anxiety, elation, relief, and single-minded determination all describe emotional responses of patients to treatment with paclitaxel (TAXOL@ [Bristol-Myers Squibb Co., Princeton, NJl) at Fox Chase Cancer Center in Philadelphia. Anything that elicits this broad range of reactions in patients also evokes ethical questions and concerns among the staff. Although less concrete than the practical issues involved in the administration of paclitaxel, these ethical concerns are no less important. This article will outline basic ethical principles, discuss their relationship to paclitaxel administration, and aim to sensitize the caregiver to various issues and concerns related to paclitaxel therapy. ETHICAL PRINCIPLES
In her 1991 article;' Christine Grady defined the broad ethical principles that surface in the conduct From the Department of Nursing, the Fox Chase Cancer Center. Philadelphia, PA. Address reprint requests to Judith Kehs Much. KN, MSN, OCN. Fox Chase Cancer Center. 7701 Burholme Ave, Philadelphia, PA 19111. Copyright © 1993 by W.B. Saunders Company 0749-2081/93/0904·2005$5.00/0
16
of clinical trials as respect for persons, nonmaleficence, beneficence, and justice. To paraphrase Grady, the principle of respect for persons relates to both autonomy and selfdetermination. An autonomous person is capable not only of deliberating about personal goals but also of acting on the results of that deliberation; such defines self-determination. As caregivers, respect for autonomy requires that we allow patients to deliberate and make their own choices, even if such choices are believed to be harmful to the individual. Interference in another person's right to self-determination is justifiable only if the choice made is harmful to someone else. For the most part, caregivers should respect and support the individual's capacity for self-determination; indeed, we show disrespect for individuals and their rights if we refuse to accept their choices. Although mature people are generally capable of self-determination, there may be occasions when an individual loses this ability as a result of illness. In that case, caregivers show respect for so-called "immature" individuals by protecting them from harm. Nonmaleficence is the strong universal obligation not to harm others. Closely linked to nonmaleficence, beneficence is the obligation to do good or to promote the good of others. In addition, beneficence involves commitment both to securing the well-being of individuals and to developing information that will provide a basis for securing the future well-being of others. Therefore, clinical trials are believed to contribute to the ethical principle of beneficence because their completion provides information that will contribute to the wellbeing of future patients. Justice-the principle of fairness-involves the equitable distribution of benefits as well as burdens unless unequal distribution is justified by either merit or need. Relationship of Ethical Principles to Paclitaxel The paclitaxel experience provides an excellent forum for illustration of basic ethical principles. Paclitaxel has had a very high media profile ,2 which reflects the belief of many that paclitaxel is the most exciting drug to become available in
Seminars in Oncology Nursing, Vol 9. No 4, Suppl 2 (November), 1993: pp 16-20
ETHICS AND PACLITAXEL ADMINISTRATION
many years. 2-6 It also reflects the complicated environmental and supply issues surrounding the drug's development. 2-5 •7 This high profile, which includes reports of successful clinical trials, has led to tremendous public demand for paclitaxel. One quotation from the Journal of the National Cancer Institute provides an example'': . . . Hundreds of inquiries for information about the drug have come in from all parts of the United States, as well as foreign countries such as Australia, the Philippines, Italy, and Spain. Most patients want to know whether paclitaxel is appropriate for them and how to get it. . . Many patients believe that paclitaxel may be their last chance for cure, regardless of their type of cancer... Some patients call regarding their worry that environmental issues will preclude their access to this new "wonder drug. " Individuals with yew trees growing on their property have offered to sell them to NCI [National Cancer Institute]. A few people want to sell just the bark. Others ask how to cultivate the trees for future sale. In addition, Native Americans have expressed concerns about yew tree harvesting on Indian property.
The strength of the public response to the media attention to paclitaxel has raised a variety of issues related to public demand for the drug, access and supply problems, and patient selection and selfreferral concerns. Alternately reflecting environmental/supply concerns and the popular characterization of paclitaxel as the most exciting drug in 10 years, caregivers have been pressured both to deliver and not to deliver the drug. From the perspective of general ethical principles, the issues of respect for persons and patients' ability to make their own decisions can clash with caregiver issues of beneficence/nonmaleficence (doing good or avoiding harm) as well as with justice and access issues. These principles and the conflicts experienced by caregivers attempting to provide their patients with access to paclitaxel are exemplified by a case in which a woman with ovarian cancer came to the outpatient clinic at Fox Chase Cancer Center stating that she had heard about paclitaxel and believed that she should be receiving it. Unfortunately, the woman did not meet the clinical trial criteria and her physician was unable to provide her with the drug. The patient's overwhelming desire for the drug not only caused difficulty in the physician-patient relationship but also created a delay in convincing the patient to accept a different treatment regimen.
17
In other examples of patient reactions, some have wanted to forgo the parameters of good medicine to obtain paclitaxel. There have been requests for paclitaxel treatment from patients only 2 weeks after cardiac catheterization, from patients who had stopped essential cardiac medication without medical advice in order to get the drug, from those who present at our clinic literally begging for paclitaxel, and from patients who have received paclitaxel induction therapy and who, after a severe hypersensitivity reaction to their second cycle of paclitaxel, nevertheless beg to risk full anaphylaxis as long as they can continue to get the drug. Additionally, some patients being treated with paclitaxel experience high levels of anxiety regarding supply and access issues, and they often display that anxiety by throwing objects in their hospital rooms and otherwise abusing staff if they feel their infusion is not started in a timely fashion. Why is there so much anxiety surrounding this drug? Why are patients-women, in particularprepared to take substantial risks to gain access to the drug and to continue to receive it? The answer may reflect the devastating impact of advanced ovarian cancer. For example, approximately 14,000 women die in the United States every year of ovarian cancer. Caregivers are in the position of telling some individuals who are poor risks for paclitaxel administration, "If you get this drug, you might die." Patients, on the other hand, say to caregivers, "If I don't get this drug, I will die." Many women we have treated see paclitaxel as their lifeline. As a result, their variations in mood often are much more extreme than those of the majority of patients receiving chemotherapy for other malignancies. Issues of access can be related to the ethical principle of justice or fairness. Until the recent release of paclitaxel, access was, to some degree, a function of both environmental and financial resources that required sophistication (ie, knowledge of and access to a center offering paclitaxel clinical trials) as well as access to appropriate health care in the first place. Both of these issues have significant implications for underserved populations. In addition, both access to paclitaxel and supply of paclitaxel have created controversial issues involving the balancing of difficult choices between beneficence for persons and maintenance of natural resources.
18
JUDITH KEHS MUCH
ACUTE VERSUS CHRONIC ILLNESS: ETHICAL CONSIDERATIONS
A 1988 Hastings Center Report, Ethical Challenges of Chronic Illness," addressed some of the dilemmas faced by caregivers involved with paclitaxel by differentiating between ethical principles of acute versus chronic illness models. Looking specifically at the principles of self-determination and respect for persons, the report concluded that persons with chronic illness must manage their illness socially and psychologically as well as medically. The process of living with chronic disease (including cancer) is more about negotiating with illness than combating disease. With a chronic disease, respect for persons includes the caregivers' sensitivity to the meaning and purpose of individual behaviors, which may not be clear or objective. Thus, the caregiver should not necessarily acquiesce to a patient's wishes if those wishes seem ill-advised. Rather, the caregiver may be able to help design another less medically harmful coping strategy. Such a strategy requires more energy on the part of the caregiver, involving, for example, investigations into ways to give an individual a means of control that is more appropriate than noncompliance or proceeding with treatment against medical advice. FUTURE CONCERNS
An examination of future concerns related to paclitaxel requires an understanding of current issues stemming from the environment, information! technology transfer, and drug supply and demand.
Environment Paclitaxel is a plant product currently made from the bark of the Taxus brevifolia, or Pacific yew tree, home to the spotted owl. The yew is an abundant but very slow-growing understory tree; it grows in the cool, shaded shelter of much taller trees, where both the yew and the owl are shielded from the sun's drying effects. The logging of larger trees has ruined the habitat of both the yew and the owl. Destruction of this ecosystem has not affected the yew and the owl alone but has also negatively affected other plant growth and, with it, the potential for other important plant discoveries that could be medically advantageous.
In paclitaxel production, it is the bark rather than the tree itself that is used. However, when the bark is stripped from the tree, the tree dies. Research is therefore under way to investigate renewable sources of the drug, such as yew needles and twigs that can be collected without killing the slow-growing tree. 2,4,6.7 Alternative methods of bulk production of paclitaxel also are currently being investigated and include cell culture, other similar trees, and increasing the rapidity of tree growth. 2-7, 1O
Drug Supply/Demand In 1991, dwindling resources prompted development of the Cooperative Research and Development Agreement (CRADA) between the National Cancer Institute (NCI) and the Bristol-Myers Squibb Company. Under the CRADA, BristolMyers Squibb Company received exclusive access to NCI clinical and preclinical paclitaxel data in order to expedite Food and Drug Administration (FDA) approval for paclitaxel as an orphan compound to treat refractory ovarian cancer. In return, Bristol-Myers Squibb Company agreed to supply paclitaxel to the NCI for clinical study, Bristol-Myers Squibb Company estimates that by 1995 production of paclitaxel will involve a semisynthetic process that will no longer rely on bark, 10 This will decrease pressure from environmental groups and allow for a consistent flow of paclitaxel independent of access to trees. Although currently only approved for the treatment of relapsed or refractory ovarian cancer, it has become clear from the success of current clinical trials that paclitaxel will play a role in treatment of other tumors (eg, head and neck,lung, and breast cancers6.11- 13) . If demand becomes excessive before large-scale semisynthetic production can be perfected, it is conceivable that demand will exceed supply.4.6 Financial/insurance resources and physician reimbursement were addressed by Bristol-Myers Squibb Company at the time of the release of the drug,lO ensuring a financial basis for access by underserved populations.
Information/Technology Transfer Concerns about information and technology transfer highlight the need for nurses to develop such contacts in a variety of settings. Nurses who
19
ETHICS AND PACLITAXEL ADMINISTRATION
have participated in paclitaxel development and clinical trials have an obligation to educate caregivers in the greater community in order to foster the sensitivity needed for handling issues related to paclitaxel administration. Nurses must be sensitive to the fact that the literature related to paclitaxel administration may be somewhat different from information gathered on an experiential or anecdotal basis. Paclitaxel comes to the community with such fanfare and in such a relatively short time that information regarding its administration can be expected to change over time, and the learning curve for health care providers in the community will be quite steep, necessitating a variety of supports, such as nursing networks involving individuals who have more experience in providing this drug. Thorough communication about all the issues surrounding paclitaxel administration is important to provide an adequate basis for both patients and caregivers to reach sound decisions about appropriate use of the drug. Open discussion by caregivers regarding the issues that arise for patients before paclitaxel therapy will be helpful in providing an understanding of factors that may confront patients and an understanding of the potential contlict encountered by the caregiver.
patient. Therefore, a licensed physician may administer and prescribe a new drug for treatment purposes without FDA interference. Such treatment may involve prescribing an approved drug for a new use, giving a drug at a different dosage, or varying the treatment conditions from those on the approved label. None of these variations require approval by an Institutional Review Board unless the physician is using the drug for research purposes. Although nurses may administer those drugs being used for treatment purposes, they are legally responsible for negligent acts of omission or commission and are not protected from liability solely on the basis of following orders written by a physician. This means that the nurse must make an independent judgment that the order for treatment is appropriate. The nurse is obligated to seek other information sources such as the pharmacy or recent journals, if necessary. The nurse must direct any questions to the prescribing physician. Nurses who are confident about their knowledge and competence to administer the drug may add a note to the chart explaining the investigative process. However, if the nurse does not feel there is sufficient information to administer the drug safely, it should be withheld. 14
Ethical and Legal Issues
CONCLUSION
There are some additional nursing issues involved in new-drug administration. Because early reports indicate the success of paclitaxel in other disease sites, nurses may find themselves in the position of administering the drug for formally unapproved indications. According to Rollins,14 when a physician prescribes a new drug, it is either for therapeutic or investigational use. The FDA may not regulate the practice of medicine between the physician and
Paclitaxel offers many patients a new and exciting treatment alternative. In the zest of media and medical community efforts to inform the public, we have certainly captured the attention of thousands of cancer patients. Those of us who have had experience in the development of this drug and investigations into its uses are obligated to communicate our knowledge to providers who are newly acquainted with paclitaxel.
REFERENCES I. Grady C: Ethical issues in clinical trials. Semin Oncol Nurs 7:288-296, 1991 2. Jaffe M: Killing the cure. Philadelphia Inquirer, February 23, 1992 3. Blume E: Government moves to increase taxol supply. J Natl Cancer Inst 83:1054-1056, 1991 4. Cragg G, Snader K: Taxol: The supply issue. Cancer Cells 2:233-235, 1991
5. Reynolds T: House subcommittee scrutinizes taxol agreements. J Natl Cancer Inst 83:1134-1135, 1991 6. Rowinsky EK, Onetto N, Canetta R, et al: Taxol: The first of the taxanes, an important new class of antitumor agents. Semin Oncol 19:646-662, 1992 7. Rowinsky EK, Donehower R: Taxol: Twenty years later the story unfolds. J Natl Cancer Inst 83:1778-1781, 1991 (editorial)
20 8. Patt 1: What the public wants to know about taxol. 1 Nat! Cancer Inst 83:905, 1991 9. lennings B, Callahan D, Caplan AL: Ethical challenges of chronic illness. Hastings Cent Rep, February-March: 1-16, 1988 (suppl) 10. Bristol-Myers Squibb Company: FDA approves taxol for US market. Columns 21(1):1, 4, 1993 11. Murphy WK, Fossella FV, Winn RI, et al: Phase II study of taxol in patients with untreated advanced non-small cell lung cancer. 1 Nat! Cancer Inst 85:384-388, 1993
JUDITH KEHS MUCH
12. Chang AY, Kim K, Glick 1, et al: Phase II study of taxol, merbarone, and piroxantrone in stage IV non-small cell lung cancer: The Eastern Cooperative Oncology Group results. 1 Nat! Cancer Inst 85:388-394, 1993 13. Holmes FA, Walters RS, Theriault RL, et al: Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. 1 Nat! Cancer Inst 83:1797-1805, 1991 14. Rollins W: What nurses should know about administering "new drugs." Nurs Law Ethics 1(6):1-2,9-11, 1980
T
HE WORDS hope, rage, desperation, anxiety, elation, relief, and single-minded determination all describe emotional responses of patients to treatment with paclitaxel (TAXOL@ [Bristol-Myers Squibb Co., Princeton, NJl) at Fox Chase Cancer Center in Philadelphia. Anything that elicits this broad range of reactions in patients also evokes ethical questions and concerns among the staff. Although less concrete than the practical issues involved in the administration of paclitaxel, these ethical concerns are no less important. This article will outline basic ethical principles, discuss their relationship to paclitaxel administration, and aim to sensitize the caregiver to various issues and concerns related to paclitaxel therapy. ETHICAL PRINCIPLES
In her 1991 article;' Christine Grady defined the broad ethical principles that surface in the conduct From the Department of Nursing, the Fox Chase Cancer Center. Philadelphia, PA. Address reprint requests to Judith Kehs Much. KN, MSN, OCN. Fox Chase Cancer Center. 7701 Burholme Ave, Philadelphia, PA 19111. Copyright © 1993 by W.B. Saunders Company 0749-2081/93/0904·2005$5.00/0
16
of clinical trials as respect for persons, nonmaleficence, beneficence, and justice. To paraphrase Grady, the principle of respect for persons relates to both autonomy and selfdetermination. An autonomous person is capable not only of deliberating about personal goals but also of acting on the results of that deliberation; such defines self-determination. As caregivers, respect for autonomy requires that we allow patients to deliberate and make their own choices, even if such choices are believed to be harmful to the individual. Interference in another person's right to self-determination is justifiable only if the choice made is harmful to someone else. For the most part, caregivers should respect and support the individual's capacity for self-determination; indeed, we show disrespect for individuals and their rights if we refuse to accept their choices. Although mature people are generally capable of self-determination, there may be occasions when an individual loses this ability as a result of illness. In that case, caregivers show respect for so-called "immature" individuals by protecting them from harm. Nonmaleficence is the strong universal obligation not to harm others. Closely linked to nonmaleficence, beneficence is the obligation to do good or to promote the good of others. In addition, beneficence involves commitment both to securing the well-being of individuals and to developing information that will provide a basis for securing the future well-being of others. Therefore, clinical trials are believed to contribute to the ethical principle of beneficence because their completion provides information that will contribute to the wellbeing of future patients. Justice-the principle of fairness-involves the equitable distribution of benefits as well as burdens unless unequal distribution is justified by either merit or need. Relationship of Ethical Principles to Paclitaxel The paclitaxel experience provides an excellent forum for illustration of basic ethical principles. Paclitaxel has had a very high media profile ,2 which reflects the belief of many that paclitaxel is the most exciting drug to become available in
Seminars in Oncology Nursing, Vol 9. No 4, Suppl 2 (November), 1993: pp 16-20
ETHICS AND PACLITAXEL ADMINISTRATION
many years. 2-6 It also reflects the complicated environmental and supply issues surrounding the drug's development. 2-5 •7 This high profile, which includes reports of successful clinical trials, has led to tremendous public demand for paclitaxel. One quotation from the Journal of the National Cancer Institute provides an example'': . . . Hundreds of inquiries for information about the drug have come in from all parts of the United States, as well as foreign countries such as Australia, the Philippines, Italy, and Spain. Most patients want to know whether paclitaxel is appropriate for them and how to get it. . . Many patients believe that paclitaxel may be their last chance for cure, regardless of their type of cancer... Some patients call regarding their worry that environmental issues will preclude their access to this new "wonder drug. " Individuals with yew trees growing on their property have offered to sell them to NCI [National Cancer Institute]. A few people want to sell just the bark. Others ask how to cultivate the trees for future sale. In addition, Native Americans have expressed concerns about yew tree harvesting on Indian property.
The strength of the public response to the media attention to paclitaxel has raised a variety of issues related to public demand for the drug, access and supply problems, and patient selection and selfreferral concerns. Alternately reflecting environmental/supply concerns and the popular characterization of paclitaxel as the most exciting drug in 10 years, caregivers have been pressured both to deliver and not to deliver the drug. From the perspective of general ethical principles, the issues of respect for persons and patients' ability to make their own decisions can clash with caregiver issues of beneficence/nonmaleficence (doing good or avoiding harm) as well as with justice and access issues. These principles and the conflicts experienced by caregivers attempting to provide their patients with access to paclitaxel are exemplified by a case in which a woman with ovarian cancer came to the outpatient clinic at Fox Chase Cancer Center stating that she had heard about paclitaxel and believed that she should be receiving it. Unfortunately, the woman did not meet the clinical trial criteria and her physician was unable to provide her with the drug. The patient's overwhelming desire for the drug not only caused difficulty in the physician-patient relationship but also created a delay in convincing the patient to accept a different treatment regimen.
17
In other examples of patient reactions, some have wanted to forgo the parameters of good medicine to obtain paclitaxel. There have been requests for paclitaxel treatment from patients only 2 weeks after cardiac catheterization, from patients who had stopped essential cardiac medication without medical advice in order to get the drug, from those who present at our clinic literally begging for paclitaxel, and from patients who have received paclitaxel induction therapy and who, after a severe hypersensitivity reaction to their second cycle of paclitaxel, nevertheless beg to risk full anaphylaxis as long as they can continue to get the drug. Additionally, some patients being treated with paclitaxel experience high levels of anxiety regarding supply and access issues, and they often display that anxiety by throwing objects in their hospital rooms and otherwise abusing staff if they feel their infusion is not started in a timely fashion. Why is there so much anxiety surrounding this drug? Why are patients-women, in particularprepared to take substantial risks to gain access to the drug and to continue to receive it? The answer may reflect the devastating impact of advanced ovarian cancer. For example, approximately 14,000 women die in the United States every year of ovarian cancer. Caregivers are in the position of telling some individuals who are poor risks for paclitaxel administration, "If you get this drug, you might die." Patients, on the other hand, say to caregivers, "If I don't get this drug, I will die." Many women we have treated see paclitaxel as their lifeline. As a result, their variations in mood often are much more extreme than those of the majority of patients receiving chemotherapy for other malignancies. Issues of access can be related to the ethical principle of justice or fairness. Until the recent release of paclitaxel, access was, to some degree, a function of both environmental and financial resources that required sophistication (ie, knowledge of and access to a center offering paclitaxel clinical trials) as well as access to appropriate health care in the first place. Both of these issues have significant implications for underserved populations. In addition, both access to paclitaxel and supply of paclitaxel have created controversial issues involving the balancing of difficult choices between beneficence for persons and maintenance of natural resources.
18
JUDITH KEHS MUCH
ACUTE VERSUS CHRONIC ILLNESS: ETHICAL CONSIDERATIONS
A 1988 Hastings Center Report, Ethical Challenges of Chronic Illness," addressed some of the dilemmas faced by caregivers involved with paclitaxel by differentiating between ethical principles of acute versus chronic illness models. Looking specifically at the principles of self-determination and respect for persons, the report concluded that persons with chronic illness must manage their illness socially and psychologically as well as medically. The process of living with chronic disease (including cancer) is more about negotiating with illness than combating disease. With a chronic disease, respect for persons includes the caregivers' sensitivity to the meaning and purpose of individual behaviors, which may not be clear or objective. Thus, the caregiver should not necessarily acquiesce to a patient's wishes if those wishes seem ill-advised. Rather, the caregiver may be able to help design another less medically harmful coping strategy. Such a strategy requires more energy on the part of the caregiver, involving, for example, investigations into ways to give an individual a means of control that is more appropriate than noncompliance or proceeding with treatment against medical advice. FUTURE CONCERNS
An examination of future concerns related to paclitaxel requires an understanding of current issues stemming from the environment, information! technology transfer, and drug supply and demand.
Environment Paclitaxel is a plant product currently made from the bark of the Taxus brevifolia, or Pacific yew tree, home to the spotted owl. The yew is an abundant but very slow-growing understory tree; it grows in the cool, shaded shelter of much taller trees, where both the yew and the owl are shielded from the sun's drying effects. The logging of larger trees has ruined the habitat of both the yew and the owl. Destruction of this ecosystem has not affected the yew and the owl alone but has also negatively affected other plant growth and, with it, the potential for other important plant discoveries that could be medically advantageous.
In paclitaxel production, it is the bark rather than the tree itself that is used. However, when the bark is stripped from the tree, the tree dies. Research is therefore under way to investigate renewable sources of the drug, such as yew needles and twigs that can be collected without killing the slow-growing tree. 2,4,6.7 Alternative methods of bulk production of paclitaxel also are currently being investigated and include cell culture, other similar trees, and increasing the rapidity of tree growth. 2-7, 1O
Drug Supply/Demand In 1991, dwindling resources prompted development of the Cooperative Research and Development Agreement (CRADA) between the National Cancer Institute (NCI) and the Bristol-Myers Squibb Company. Under the CRADA, BristolMyers Squibb Company received exclusive access to NCI clinical and preclinical paclitaxel data in order to expedite Food and Drug Administration (FDA) approval for paclitaxel as an orphan compound to treat refractory ovarian cancer. In return, Bristol-Myers Squibb Company agreed to supply paclitaxel to the NCI for clinical study, Bristol-Myers Squibb Company estimates that by 1995 production of paclitaxel will involve a semisynthetic process that will no longer rely on bark, 10 This will decrease pressure from environmental groups and allow for a consistent flow of paclitaxel independent of access to trees. Although currently only approved for the treatment of relapsed or refractory ovarian cancer, it has become clear from the success of current clinical trials that paclitaxel will play a role in treatment of other tumors (eg, head and neck,lung, and breast cancers6.11- 13) . If demand becomes excessive before large-scale semisynthetic production can be perfected, it is conceivable that demand will exceed supply.4.6 Financial/insurance resources and physician reimbursement were addressed by Bristol-Myers Squibb Company at the time of the release of the drug,lO ensuring a financial basis for access by underserved populations.
Information/Technology Transfer Concerns about information and technology transfer highlight the need for nurses to develop such contacts in a variety of settings. Nurses who
19
ETHICS AND PACLITAXEL ADMINISTRATION
have participated in paclitaxel development and clinical trials have an obligation to educate caregivers in the greater community in order to foster the sensitivity needed for handling issues related to paclitaxel administration. Nurses must be sensitive to the fact that the literature related to paclitaxel administration may be somewhat different from information gathered on an experiential or anecdotal basis. Paclitaxel comes to the community with such fanfare and in such a relatively short time that information regarding its administration can be expected to change over time, and the learning curve for health care providers in the community will be quite steep, necessitating a variety of supports, such as nursing networks involving individuals who have more experience in providing this drug. Thorough communication about all the issues surrounding paclitaxel administration is important to provide an adequate basis for both patients and caregivers to reach sound decisions about appropriate use of the drug. Open discussion by caregivers regarding the issues that arise for patients before paclitaxel therapy will be helpful in providing an understanding of factors that may confront patients and an understanding of the potential contlict encountered by the caregiver.
patient. Therefore, a licensed physician may administer and prescribe a new drug for treatment purposes without FDA interference. Such treatment may involve prescribing an approved drug for a new use, giving a drug at a different dosage, or varying the treatment conditions from those on the approved label. None of these variations require approval by an Institutional Review Board unless the physician is using the drug for research purposes. Although nurses may administer those drugs being used for treatment purposes, they are legally responsible for negligent acts of omission or commission and are not protected from liability solely on the basis of following orders written by a physician. This means that the nurse must make an independent judgment that the order for treatment is appropriate. The nurse is obligated to seek other information sources such as the pharmacy or recent journals, if necessary. The nurse must direct any questions to the prescribing physician. Nurses who are confident about their knowledge and competence to administer the drug may add a note to the chart explaining the investigative process. However, if the nurse does not feel there is sufficient information to administer the drug safely, it should be withheld. 14
Ethical and Legal Issues
CONCLUSION
There are some additional nursing issues involved in new-drug administration. Because early reports indicate the success of paclitaxel in other disease sites, nurses may find themselves in the position of administering the drug for formally unapproved indications. According to Rollins,14 when a physician prescribes a new drug, it is either for therapeutic or investigational use. The FDA may not regulate the practice of medicine between the physician and
Paclitaxel offers many patients a new and exciting treatment alternative. In the zest of media and medical community efforts to inform the public, we have certainly captured the attention of thousands of cancer patients. Those of us who have had experience in the development of this drug and investigations into its uses are obligated to communicate our knowledge to providers who are newly acquainted with paclitaxel.
REFERENCES I. Grady C: Ethical issues in clinical trials. Semin Oncol Nurs 7:288-296, 1991 2. Jaffe M: Killing the cure. Philadelphia Inquirer, February 23, 1992 3. Blume E: Government moves to increase taxol supply. J Natl Cancer Inst 83:1054-1056, 1991 4. Cragg G, Snader K: Taxol: The supply issue. Cancer Cells 2:233-235, 1991
5. Reynolds T: House subcommittee scrutinizes taxol agreements. J Natl Cancer Inst 83:1134-1135, 1991 6. Rowinsky EK, Onetto N, Canetta R, et al: Taxol: The first of the taxanes, an important new class of antitumor agents. Semin Oncol 19:646-662, 1992 7. Rowinsky EK, Donehower R: Taxol: Twenty years later the story unfolds. J Natl Cancer Inst 83:1778-1781, 1991 (editorial)
20 8. Patt 1: What the public wants to know about taxol. 1 Nat! Cancer Inst 83:905, 1991 9. lennings B, Callahan D, Caplan AL: Ethical challenges of chronic illness. Hastings Cent Rep, February-March: 1-16, 1988 (suppl) 10. Bristol-Myers Squibb Company: FDA approves taxol for US market. Columns 21(1):1, 4, 1993 11. Murphy WK, Fossella FV, Winn RI, et al: Phase II study of taxol in patients with untreated advanced non-small cell lung cancer. 1 Nat! Cancer Inst 85:384-388, 1993
JUDITH KEHS MUCH
12. Chang AY, Kim K, Glick 1, et al: Phase II study of taxol, merbarone, and piroxantrone in stage IV non-small cell lung cancer: The Eastern Cooperative Oncology Group results. 1 Nat! Cancer Inst 85:388-394, 1993 13. Holmes FA, Walters RS, Theriault RL, et al: Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. 1 Nat! Cancer Inst 83:1797-1805, 1991 14. Rollins W: What nurses should know about administering "new drugs." Nurs Law Ethics 1(6):1-2,9-11, 1980