The Professional
Role for Nurses in Clinical
Trials
Mary Dee McEvoy, Lorelei Cannon, and Mary Lou MacDermott
LINICAL TRIALS, although initiated in the eighteenth century when the use of oranges and lemons proved efficacious in the treatment of scurvy, have increasedin scopeand complexity in the last 3 decades.’ The clinical trial is a method of research, the ultimate goal of which is the determination of the effectiveness of a specific treatment. Clinical trials are comprised of two major components:a treatmentcomponent and a research component.2 Clinical trial research involves the coordinated effort of a team including the principal investigator (usually a physician), researchnurse, clinical nurse, data manager,statistician, and pharmacist. The oncology nurse plays a major role in the development and implementation of clinical trials. Nursing participation in clinical trials is a challenging one. It calls forth the nurse’s expert skill in observation and synthesisof knowledge to identify trends in data and to develop nursing care unique to the therapy being studied. Nurses in various roles interact with patients on clinical trials. The nurse may be a data manager,the clinical nurse, or a nurse researcher. This article will address the role of the nurse as a clinician, administrator, and researcher. The role of the nurse in clinical trials research relates to the experience of the patient who elects to undertake a clinical trial. Figure 1 outlines the patient’s experience in clinical trials. First, the patient is at a point in treatment in which treatment options are discussed. This may be either at the initial diagnosis when there is no standardtherapy, or at a turning point where the treatment has been
C
From the Division of HematologyiOncology, Hospital of the University of Pennsylvania, Philadelphia, PA. Mary Dee McEvoy, PhD, RN: Clinical Director, Ambulatory Oncology, Division of HematologylOncology, Hospital of the University of Pennsylvania; Lorelei Cannon, BS, RN: Research Nurse, Division of HematologylOncology, Hospital of the University of Pennsylvania; Mary Lou MacDemott, BS, RN: Research Nurse, Division of HematologylOncology, Hospital of the University of Pennsylvania. Address reprint requests to Mary Dee McEvoy, RN, PhD, 531 Main St, Apt 1820, Roosevelt Island, NY 10044. Copyright 0 1991 by W.B. Saunders Company 0749-2081191/0704-0006$5.0010
268
judged to be ineffective, or at the time of disease recurrence. In any of these cases, the patient is feeling overwhelmed and the senseof urgency to “do something” is foremost. At this time, treatment options are discussedand the patient is offered the choice of no treatment, standard treatment with known risks and benefits if it exists, or an experimental treatment within the context of a clinical trial. Gelber and Goldhirsch note that clinical trials are a valid treatmentoption in certain selected instances because many standard treatments have extremely small response rates. The initial discussion of treatment options is a lengthy one, as the risks and benefits of each treatment must be examined in light of the patient’s goals and values. If the clinical trial offered is a phaseI trial, the risks and benefits mayebediscussedonly in theoretical terms basedon the data gleanedfrom animal models or analogousstudies of early tumor data. In phaseII trials the risks may be known, but the benefits are unknown. In phase III trials, the risks may be known, but the benefits are only partially known, ie, that the treatment is effective againsta specific tumor type, but it’s effectiveness relative to other treatmentsis unknown; the question of superiority needsto be answered. The patient who elects a treatmentwithin a clinical trial then undergoesan eligibility evaluation. This may be simple or highly complex, depending on the treatment being considered. For example, patients participating in the phase II trial of interleukin 2 with or without lymphokine-activatedkiller (LAK) cells neededto undergo a CT scan of the head and body, pulmonary function tests, electrocardiogram, and in some instances, a cardiac catheterization. This time is one of hope and anticipation for the patients as they are simultaneously worried about their underlying cancer as well as whether or not they will be eligible for the treatment they hope will be effective. Those who are judged ineligible return, with great disappointment, to another discussion of the treatment options. Thosewho are determinedto be eligible then undertakethe treatment. The treatmentphasemay be either very long and highly complex, as in treatmentsrequiring lengthy hospital stays or the confines of an intensive care
.%minars in Oncology Nursing, Vol 7, No 4 (November),
1991: pp 268-274
PROFESSIONAL
ROLE FOR NURSES
Treatment
Eligibility
TRIALS
CLINICAL ROLE
Patient Educator
1 Evaluation
\
/
Not Eligible I
Evaluation
No Response-
Return
r to Origmal
OptIons: 1 No Treatment
Fig 1. tive.
Participation
269
Options
Ehglble I
Treatment
IN CLINICAL
in clinical
trials:
2. Different
Trial
3. Standard
Treatment
the patient’s
perspec-
unit, or easily tolerated treatmentsadministered in the ambulatory care setting. At the completion of treatment, the patient is evaluated within the parametersof the protocol. If the patient responds to the treatment, he or she may be offered a specific number of treatment cycles. Even patients who respond to treatment may not be offered unlimited cycles if the protocol does not warrant it.4 The patient then undergoes a lengthy follow-up period during which tests that may not usually be performed are done becauseof protocol requirements. At each step in the clinical trial process, the nurse plays a key role in assisting the patient to understand and complete the protocol requirements. Nurses in various settings interact at different levels in achieving this common goal. The nursein the ambulatory setting performs the role of patient educator, patient advocate, and direct care giver. The researchnurse performs the role of coordinator, educator, patient advocate, and perhaps direct care giver. The inpatient staff nurse also performs each of theseroles. The researchnurse is responsible for coordinating the nursing care so that the treatment goals are clearly understoodand the patient receives the optimum nursing care. Each nurse administers patient care with a commitment to the research question underlying the treatment. Without such commitment, the question may not be answered and the patient’s efforts are then futile. Each nursing role will be discussedin turn.
Patient and family education is a cornerstoneto the decision of the patient to participate in a trial. On one hand, some patients are overly eager to participate in clinical trials feeling that a new treatment surely has more benefit than an old treatment. On the other hand, patients may be reluctant to participate becausethey fear they are being used as “guinea pigs.” It is essential that the patient’s orientation to clinical trials be determined early in the education process so that fears and anxieties may be addressed.Patient education is a collaborative effort betweenthe nursesand the physician. Education encompassesthe treatment itself, as well as the researchprotocol.5 In most instances, patients are initially concernedabout the nature of the treatmentasthat assistsin determining the risks and benefits. However, specifics about the researchprotocol should not be overlooked. The treatmentexplanation includes the patient’s anticipated experiencewhile undergoing treatment including explicit details of the treatment regimen and the side effects likely to be experienced. The treatmentregimen involves the details of the treatment such as where it will be delivered, the frequency of delivery, and who will administer the treatment.This aspectof the educational processis similar to that for any treatmentregimen. The particulars of the treatment processare crucial in decision making becausemany clinical trials are offered only through large comprehensive cancer centers. Thus, many patients must travel a great distanceto partake in the treatment. Issuessuch as cost and time of travel, living away from home, and additional living expensessuch as parking and baby-sitters are all important aspectsof the decision. It may be part of the nurse’s role to assistthe patient in planning for time away from home. Information on the side effects of treatment will vary according to the particular type of trial addressed.In phaseI trials (as described by Jenkins and Hubbard elsewherein this issue), specific information about the side effects in humansis often limited and information must be gleaned from animal studies to hypothesize potential side effects. If a treatmentis a memberof a classof drugs, such as colony-stimulating factors, information regarding side effects occasionally may be generalized from that already known regarding the other drugs
McEVOY,
of the same class. The section on background information in the written protocol provides the rationale for the study and relevant references. These references are the initial starting point for reviewing the literature and developing a theoretical side effect profile. In phase II studies, side effects have already been delineated in the prior phase I studies of the drug and may be the basis for the discussion of the side effects with patient and family members. However, since phase I studies involve only a limited number of patients, caution must be used in labeling side effects as “usual” or “rare” and it is important to explain that in all likelihood, not all the potential side effects for a treatment have been identified. Patient and family education of the research process is also important. The research process includes the goals of the study, differentiating between the phases of study, and special requirements of the study such as randomization. Also included in this discussion is the informed consent process. Although the physician has the ultimate responsibility for obtaining informed consent, the nurse participates in helping the patient understand the consent process, answering questions regarding the protocol, and helping to determine the extent of the patient’s comprehension. The goals of the study should be consistent with the goals of the patient for participating in the study. It has been shown that patients participate in clinical trials for many reasons including to help others by contributing to science, to try all options, and to get the best medical care.6-8 A patient who articulates a goal of cure while enrolling in a phase I study must understand that the purpose of phase I studies is to determine toxicity. Efficacy of the treatment is most often unknown and can only be theorized. Cure is highly unlikely. Indeed, in a retrospective study analyzing complete and partial response rates in phase I studies, Estey et al9 found that only 2% of 1248 patients had a response to treatment. Hence, it is clear that information on the purpose of the study must be clearly explained to patients. lo With this understanding, the patients may still desire to participate and may still hope for cure, but at the very least they understand and accept the trial purpose. Randomization of patients enrolled in phase III trials is also a difficult concept for some patients to accept. In some instances, patients visit a cancer center for the explicit purpose of receiving a treat-
CANNON,
AND MAcDERMOTT
ment they have read about in the popular literature. If that treatment is only offered within the confines of a clinical trial, the patient may have to partake in the randomization process. The treatment desired may not be the treatment to which they are randomized. This may preclude their willingness to be randomized. Such conflicts and issues must be sorted out in the educational process so that all are committed to the treatment as well as the question addressed in the trial. Thus, it is clear that the educational process is a complex task. Nurses involved in the care of patients at each point in the treatment process must be knowledgeable of the treatment itself and the research process. Education is begun in the ambulatory care clinic by the physician, nurse, clinical nurse specialist, research nurse, and/or chemotherapy nurse. However, each member of the team may have different responsibilities for education depending on the organizational structure of the institution. It is imperative that the nurse understand his or her own beliefs and values regarding clinical trials. i ’ An attitude devaluing clinical trials will be readily conveyed and will have an impact on the commitment that others develop toward clinical research and indeed toward the care of the patient. Direct
Care Giver
The treatment outlined in the clinical trial may be administered in the ambulatory care center12 or in the hospital. Inpatient settings may include the oncology unit, an intensive care unit, clinical research center, or other inpatient units. Regardless of the setting, the nursing care of the patient involves assessment, planning, intervention, and evaluation. Nurses in different roles may have responsibilities of different phases of the nursing process; however, the total process must be performed with care and precision. The research nurse is in a special position to influence the plan for the patient’s nursing care. Consultation with the clinical nurse specialist is valuable in developing a plan for the anticipated side effects that are outside the expertise of the research or staff nurse. Delivering the actual experimental treatment may be the role of the research nurse, staff nurse, or chemotherapy nurse. In any case, the treatment must be delivered according to the protocol. l3 Often others may be involved at the time the treatment is administered, such as pharmacists who are doing
PROFESSIONAL ROLE FOR NURSES IN CLINICAL TRIALS
pharmacokinetic studiesor basic scientists who are collecting blood samplesfor a companion study. A particularly crucial role of the nurse in clinical trials is the determination of toxicities.14 It is the nurses’ observation of the patient after treatment that identifies the side effect profile and will ultimately be the basis for the care plan of patients on the experimental treatment in the future. The documentation of side effects has direct impact on the decision regarding the Maximally Tolerated Dose (MTD) in phase I trials. This is truly a most exciting aspectof participation in clinical trials. Astute observation of each patient and the synthesis of observations across patients is the nature of nursing scholarship in clinical trials. It is the nurse that may be the first to recognize a side effect, perhaps even before the patient is aware of the experience. Delineating a primary nurse to provide care to patients undergoing the sameclinical trial would maximize the opportunity to identify commonalities of patient experiences. As the research nurse or staff nurse is documenting the patient’s responseto treatment, trends in data may become evident and interventions planned to alleviate dose-limiting side effects. Patient Advocate
A primary role of the nurse caring for patients in clinical trials is that of patient advocate.14It has been suggestedthat cancerpatients are particularly vulnerable becauseof their diagnosis and all the implications associated with cancer. l5 Indeed, some patients wish to try anything to treat their disease.Thus it is imperative that such vulnerable patients not be taken advantageof in the clinical trials arena. The informed consentprocess,as discussed by Grady elsewhere in this issue, is designed to ensure that patients’ rights are upheld. Considerable literature has evolved discussing the protection of patients’ rights and the astute researchnurse will be knowledgeable in this area. One aspect of the patient advocate role is to assistpatients in defining their own goals and purposes for participating in a clinical trial. It is important to reaffirm this as the treatment progresses and patients reevaluate their decision to participate. The reevaluation of their original decision may be a source of anxiety for the nurse as she feels that it is crucial that the patient remain on study. Indeed, patients who decide to go off study may hamper the progressof the clinical trial. Yet,
271
patients must understand that they may withdraw at any time and suffer no repercussionsfrom the health care team. Patients who begin to give indications that they wish to withdraw require special attention. Such questionsmay be an indication of other underlying problems, such as fatigue, difficulty tolerating the side effects of the treatment, loneliness, or confusion. Initiating discussion with an open mind for the purposeof clarifying the nature of the problem is a helpful, nonthreatening approach. Often such discussionshelp the patient reaffirm the initial reasons for participating and, with assurance that more effective and creative ways of managing the side effects of treatment will be given, the patient may desire to continue treatment. However, for those patients who indeed wish to discontinue treatment. that decision must be honored. Coordinator
Coordination of the protocol and the patients’ carecan be extremely complex. The researchnurse must be familiar with all aspectsof the treatment processand coordinate the care of many different hospital units, including patient care areas, blood bank, pharmacy, laboratory, and outpatient clinic. It is important to note that the attention given patients during this coordination is one of the benefits that patients perceive from participating in clinical trials.’ Their health care is well coordinated and planned. Without clear communication between departments,the patient may receive confusing or contradictory information and health care can become fragmented. In summary, the clinical role of the nurse involved in clinical trials is extensive and complex involving the roles of educator, direct care giver, advocate, and coordinator. The nurse must be interested in the progress of cancer treatment and excited about the opportunity to provide nursing care in situations that are new and ambiguous. Astute powers of observation and synthesis are required. Knowledge of philosophical approachesto treatmentsand reasonswhy patients participate in experimental therapies is essential for the nurse in understanding each patient’s reason for participation. ADMINISTRATIVE
The nurse plays a major role in the administration of the clinical trial. She is a crucial memberof
272
the protocol team and is often the individual toward whom all others turn for guidance. Although this may at times be construedastedious, it is most essential, for the data must be valid and consistent for the researchquestion to be answered. Components of the administrative role include the coordination of the patient’s care as well as the coordination of the researchproject. Coordination of the research protocol can be multifaceted. Abdellahi6 lists several areasessential for the effective managementof clinical trials, including definitions of functions and separationof responsibilities, communication structure, welldefined decision making, and identification of goals to measureprogress. The nurse must interact with professionals from many disciplines and is often the first person to be contacted with questions regarding the initiation and progress of the study. It is essential that information be readily available and disseminatedto others. The nurse may also be the first contact of the institution with the public. With clinical alerts now part of the dissemination of research findings by the National Cancer Institute,17 consumers are more aware of treatment options available. They will often call the research nurse for information on the type of clinical trials offered. If the study is a single-institution study, the nurse coordinates planning with the sponsoring agencyand the primary institution. The sponsoring agency may be a drug corporation or a major institution such as the National Cancer Institute. The nurse meets with the team involved in the study and critiques and answers questions about implementation feasibility. Suggestions regarding changes in reporting mechanisms or managing missing data are incorporated into the final document. Knowledge of the primary institution is essential, for if a study is not feasible, it should not be attempted. Data managementmay be an essential part of the role of the research nurse, or it may be delegated to a non-nurse data manager.18The consistent managementof the data allows the study question to be answeredpromptly and efficiently. This involves developing and completing data entry forms, retrieving data from records, and documenting data on appropriate forms. Characteristics of the nurse in performing the administrative role of a clinical trial includes the
McEVOY,
CANNON,
AND MAcDERMOTT
ability to interact comfortably with a variety of professionalsand to organize and implement group meetings. Organization and attention to detail is required to manageand record data forms. Knowledge of reporting mechanismsof toxic side effects and of how eachpiece of data collected impacts on the researchquestion is important. RESEARCH ROLE
The researchrole for the nurse in clinical trials is undergoing change and transition. The purpose of medical researchis to test and evaluate new treatments. The purpose of nursing researchis to evaluate patients’ responsesto treatment or disease. Previously, nurses involved in clinical trials were seenas doing medical research, simply collecting data for physicians. As the role has evolved, no one can doubt the essential component of nursing care delivered to patients and the scholarly advances nurses have made toward the delineation and treatment of symptoms. Indeed, symptom managementis a major component of oncology nursing practice, and nurses involved in clinical trials are key to delineating interventions that are effective. Researchroles that are undertakenby the clinical trials nurse may vary depending on the amountof educationalpreparationof the nurse, the nature of the team involvement, and resources available to the nurse. Fawcett” notes that research activities involve the generation of knowledge, dissemination of knowledge, and utilization of knowledge. The research nurse participates in all three activities in varying degrees. The activities involved in the implementation of the trials are crucial to the generation of knowledge, regarding both medical treatment and nursing care. Data collection offers the opportunity for the nurse to identify trends in the patient experience. Such trends will lead to the scholarly pursuit of analysis and subsequentquestioning the reason for the side effect. Such questions as why patients experienceone side effect and not another or why somepatients seemingly experienceno side effects form interesting researchquestions. At what point during the treatment are the side effects more severe, or perhaps, not more severe, but more distressing? Is the whole experience intolerable or easily tolerable for patients? What are the emotional and financial costs of the treatments?Ques-
PROFESSIONAL
ROLE FOR NURSES
IN CLINICAL
TRIALS
tions such as these arise from the nurse reflecting on the patients’ experience during the data collection and recording process. The nurse in clinical trials research is in the enviable position of providing care for patients experiencing the samedisease and treatment and can identify trends in the patients’ experience. Such examination is termed clinical scholarship and mandates that the nurse document and write about the patients’ experience. Although not a formal researchstudy, such reflections written in a scholarly fashion lead one to greater understanding of the patients’ experience and may becomethe impetus for a formal research study. Formal researchstudies are designedto answera question of relevance to the science of nursing. It is becoming more common for clinical trials researchto have a nursing component or a companion study, as discussedby Ferrell and Cohen elsewhere in this issue. The companion study is usually derived from the primary study but asks a particular nursing question. Quality-of-life research is becoming increasingly applicable to this category. It is appropriate for many studiesto have a quality of life aspect that may come under the realm of nursing. The interest in implementing studies of quality of life evolved as it becamerecognized that sometreatmentsmay prolong life but with a reduction in quality. Alternatively, some treatments, although not improving patient survival, may improve the quality of that survival.*’ Quality-of-life literature is extensive and controversial. The use of tools to measurelife’s quality must be carefully chosen with the endpoint in mind. Dean2’ cautions the use of quality of life as an outcome measure in clinical trials research, identifying the political ramifications of such use. She states that quality-of-life indicators may be used for the purpose of allocating health care resources.To her, this is particularly problematic in view of the questions surrounding quality-of-life research such as the type of measurementsused, the person doing the measurements,and when the measurementsare taken. Despite the problems regarding quality-of-life research, the addition of this component to clinical trials recognizesand affirms that treatmentsare experiencedin the context of one’s life and impact on that quality. Another type of companion study that might prove fruitful is descriptive studies regarding the
273
side effects of treatments. Several authors have studied treatment side effects in a descriptive fashion and provide useful models for incorporation into clinical trials. Such studies will provide the basisfor the nursing care should the treatmentgain widespread use. Additionally, companion studies may be designed to evaluate the effectiveness of nursing interventions within particular treatments. The clinical trials involving highly emetic drugs may give rise to companion studies on behavioral interventions to reduce nausea. An alternative to the companion study is one that is totally distinct from the main study, but uses the subjectsenrolled in the clinical trial to answer a nursing question. In this instance, data will be gathered, recorded, and analyzed separately from the main study. Such research may be basic science research or theoretical research. A body of literature that may be fruitful to pursue is the question of motivation for entering clinical trials and for remaining in clinical trials. This requires a nurse as the principle investigator who is separate from the researchteam. Often, the nurse involved in clinical trials is involved in the dissemination of the research findings. Writing researchreports, abstracts,and preparing poster sessionscan be a rewarding finish to a clinical trial in which so much effort has been expended. Presenting papers or being present at poster sessionsenablesthe nurse to answer scientific and clinical questionsregarding the study design, implementation, and analysis. Qualities of the nurse in implementing the researchcomponentof a clinical trial includes ability and easein reading researchreports, understanding the research process, and ability to coordinate a researchprogram. SUMMARY
This article has examined the role of the nurse in clinical trials, particularly the clinical, administrative, and research roles. Components of each role and characteristics essential for the implementation of each role have been examined. The nursing role in clinical trials research is undergoing major transformation from the perception of the nurse as a data collector for medical research to the recognition of the nurse as an essentialmember of the researchteam with a multifaceted role.
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Miaskowski22 identifies two factors influencing the development of oncology nursing practice; scientific and technological advances and societal factors relating to the perception of cancer as a diseaseand changesin the nursing profession. Certainly it is recognizedthat progressin basic science
CANNON,
AND MAcDERMOTT
researchwill lead to an increasein the complexity and number of clinical trials. Nurses have clearly implemented the roles necessaryto be vital participants and have contributed to answeringquestions leading to improved treatmentsfor the patient with cancer.
REFERENCES 1. Friedman LM, Furberg CD, DeMets DL: Fundamentals of Clinical Trials (ed 2). Littleton, MA, PSG, 1981 2. Leventhal B: An overview of clinical trials in oncology. Semin Oncol 15:414-422, 1988 3. Gelber R, Goldhirsch A: Can a clinical trial be the treatment of choice for patients with cancer? J Nat1 Cancer lnst 80:12, 1988 4. Grinnell F: Endings of clinical research protocols: Distinguishing therapy from research. IRB: Rev Hum Sub Res 12: l3, 1990 5. Bujorian G: Clinical trials: Patient issues in the decisionmaking process. Oncol Nurs Forum 15:779-783, 1988 6. Markman M: The ethical dilemmas of Phase I clinical trials. CA 36:367-369, 1986 7. Mattson ME, Curb JD, McArdle R, et al: Participation in a clinical trial: The patient’s point of view. Controlled Clin Trials 6:156-167, 1985 8. Cassileth BR, Lusk El, Miller DS, et al: Attitudes toward clinical trials among patients and the public. J Am Med Assoc 248:968-970, 1982 9. Estey E, Hoth D, Leyland-Jones B, et al: Therapeutic results in Phase I studies. Proc Am Sot Clin Oncol 3:35, 1984 (abstr) 10. Friedman B: Cohort specific consent: An honest approach to Phase I clinical cancer studies. IRB: Rev Hum Subj Res 12:5-7, 1990 11. Jassak P, Ryan M: Ethical issues in clinical research. Semin Oncol Nurs 5:102-108, 1989
12. Harris TM, Bean C: Changing the role of the nurse in the Hematology-Oncology outpatient setting. Oncol Nurs Forum 18:43-49, 1991 13. Hubbard S: Cancer treatment research: The role of the nurse in clinical trials of cancer therapy. Nurs Clin North Am 17:763-783, 1982 14. Gross J: Clinical research in cancer chemotherapy. Onco1 Nurs Forum 13:59-65, 1986 15. Benoliel JQ: The cancer patient’s right to know and decide: An ethical perspective, in McCorkle R, Hongladarom G (eds): Issues and Topics in Cancer Nursing. Norwalk, CT, Appleton-Century-Crofts, 1986, pp 5-17 16. Abdellah F: Management of clinical trials. J Prof Nurs 6:189, 1990 17. Wittenberg C: Experts debate guidelines for release of research information. J Nat1 Cancer lnst 82:4, 1990 18. White-Hershey D, Nevidjon B: Fundamentals of oncology nurse/data managers-Preparing for a new role. Oncol Nurs Forum 17:371-379, 1990 19. Fawcett J: A typology of nursing research activities according to educational preparation. J Prof Nurs 1:75-78, 1985 20. Vanchieri C: Quality of life gets equal consideration as a clinical trial endpoint. J Nat1 Cancer lnst 82:4, 1990 21, Dean H: Political and ethical implications of using quality of life as an outcome measure. Semin Oncol Nurs 6:303308, 1990 22. Miaskowski C: The future of oncology nursing: A historical perspective. Nurs Clin North Am 25:461-473, 1990
Role for Nurses in Clinical
Trials
Mary Dee McEvoy, Lorelei Cannon, and Mary Lou MacDermott
LINICAL TRIALS, although initiated in the eighteenth century when the use of oranges and lemons proved efficacious in the treatment of scurvy, have increasedin scopeand complexity in the last 3 decades.’ The clinical trial is a method of research, the ultimate goal of which is the determination of the effectiveness of a specific treatment. Clinical trials are comprised of two major components:a treatmentcomponent and a research component.2 Clinical trial research involves the coordinated effort of a team including the principal investigator (usually a physician), researchnurse, clinical nurse, data manager,statistician, and pharmacist. The oncology nurse plays a major role in the development and implementation of clinical trials. Nursing participation in clinical trials is a challenging one. It calls forth the nurse’s expert skill in observation and synthesisof knowledge to identify trends in data and to develop nursing care unique to the therapy being studied. Nurses in various roles interact with patients on clinical trials. The nurse may be a data manager,the clinical nurse, or a nurse researcher. This article will address the role of the nurse as a clinician, administrator, and researcher. The role of the nurse in clinical trials research relates to the experience of the patient who elects to undertake a clinical trial. Figure 1 outlines the patient’s experience in clinical trials. First, the patient is at a point in treatment in which treatment options are discussed. This may be either at the initial diagnosis when there is no standardtherapy, or at a turning point where the treatment has been
C
From the Division of HematologyiOncology, Hospital of the University of Pennsylvania, Philadelphia, PA. Mary Dee McEvoy, PhD, RN: Clinical Director, Ambulatory Oncology, Division of HematologylOncology, Hospital of the University of Pennsylvania; Lorelei Cannon, BS, RN: Research Nurse, Division of HematologylOncology, Hospital of the University of Pennsylvania; Mary Lou MacDemott, BS, RN: Research Nurse, Division of HematologylOncology, Hospital of the University of Pennsylvania. Address reprint requests to Mary Dee McEvoy, RN, PhD, 531 Main St, Apt 1820, Roosevelt Island, NY 10044. Copyright 0 1991 by W.B. Saunders Company 0749-2081191/0704-0006$5.0010
268
judged to be ineffective, or at the time of disease recurrence. In any of these cases, the patient is feeling overwhelmed and the senseof urgency to “do something” is foremost. At this time, treatment options are discussedand the patient is offered the choice of no treatment, standard treatment with known risks and benefits if it exists, or an experimental treatment within the context of a clinical trial. Gelber and Goldhirsch note that clinical trials are a valid treatmentoption in certain selected instances because many standard treatments have extremely small response rates. The initial discussion of treatment options is a lengthy one, as the risks and benefits of each treatment must be examined in light of the patient’s goals and values. If the clinical trial offered is a phaseI trial, the risks and benefits mayebediscussedonly in theoretical terms basedon the data gleanedfrom animal models or analogousstudies of early tumor data. In phaseII trials the risks may be known, but the benefits are unknown. In phase III trials, the risks may be known, but the benefits are only partially known, ie, that the treatment is effective againsta specific tumor type, but it’s effectiveness relative to other treatmentsis unknown; the question of superiority needsto be answered. The patient who elects a treatmentwithin a clinical trial then undergoesan eligibility evaluation. This may be simple or highly complex, depending on the treatment being considered. For example, patients participating in the phase II trial of interleukin 2 with or without lymphokine-activatedkiller (LAK) cells neededto undergo a CT scan of the head and body, pulmonary function tests, electrocardiogram, and in some instances, a cardiac catheterization. This time is one of hope and anticipation for the patients as they are simultaneously worried about their underlying cancer as well as whether or not they will be eligible for the treatment they hope will be effective. Those who are judged ineligible return, with great disappointment, to another discussion of the treatment options. Thosewho are determinedto be eligible then undertakethe treatment. The treatmentphasemay be either very long and highly complex, as in treatmentsrequiring lengthy hospital stays or the confines of an intensive care
.%minars in Oncology Nursing, Vol 7, No 4 (November),
1991: pp 268-274
PROFESSIONAL
ROLE FOR NURSES
Treatment
Eligibility
TRIALS
CLINICAL ROLE
Patient Educator
1 Evaluation
\
/
Not Eligible I
Evaluation
No Response-
Return
r to Origmal
OptIons: 1 No Treatment
Fig 1. tive.
Participation
269
Options
Ehglble I
Treatment
IN CLINICAL
in clinical
trials:
2. Different
Trial
3. Standard
Treatment
the patient’s
perspec-
unit, or easily tolerated treatmentsadministered in the ambulatory care setting. At the completion of treatment, the patient is evaluated within the parametersof the protocol. If the patient responds to the treatment, he or she may be offered a specific number of treatment cycles. Even patients who respond to treatment may not be offered unlimited cycles if the protocol does not warrant it.4 The patient then undergoes a lengthy follow-up period during which tests that may not usually be performed are done becauseof protocol requirements. At each step in the clinical trial process, the nurse plays a key role in assisting the patient to understand and complete the protocol requirements. Nurses in various settings interact at different levels in achieving this common goal. The nursein the ambulatory setting performs the role of patient educator, patient advocate, and direct care giver. The researchnurse performs the role of coordinator, educator, patient advocate, and perhaps direct care giver. The inpatient staff nurse also performs each of theseroles. The researchnurse is responsible for coordinating the nursing care so that the treatment goals are clearly understoodand the patient receives the optimum nursing care. Each nurse administers patient care with a commitment to the research question underlying the treatment. Without such commitment, the question may not be answered and the patient’s efforts are then futile. Each nursing role will be discussedin turn.
Patient and family education is a cornerstoneto the decision of the patient to participate in a trial. On one hand, some patients are overly eager to participate in clinical trials feeling that a new treatment surely has more benefit than an old treatment. On the other hand, patients may be reluctant to participate becausethey fear they are being used as “guinea pigs.” It is essential that the patient’s orientation to clinical trials be determined early in the education process so that fears and anxieties may be addressed.Patient education is a collaborative effort betweenthe nursesand the physician. Education encompassesthe treatment itself, as well as the researchprotocol.5 In most instances, patients are initially concernedabout the nature of the treatmentasthat assistsin determining the risks and benefits. However, specifics about the researchprotocol should not be overlooked. The treatmentexplanation includes the patient’s anticipated experiencewhile undergoing treatment including explicit details of the treatment regimen and the side effects likely to be experienced. The treatmentregimen involves the details of the treatment such as where it will be delivered, the frequency of delivery, and who will administer the treatment.This aspectof the educational processis similar to that for any treatmentregimen. The particulars of the treatment processare crucial in decision making becausemany clinical trials are offered only through large comprehensive cancer centers. Thus, many patients must travel a great distanceto partake in the treatment. Issuessuch as cost and time of travel, living away from home, and additional living expensessuch as parking and baby-sitters are all important aspectsof the decision. It may be part of the nurse’s role to assistthe patient in planning for time away from home. Information on the side effects of treatment will vary according to the particular type of trial addressed.In phaseI trials (as described by Jenkins and Hubbard elsewherein this issue), specific information about the side effects in humansis often limited and information must be gleaned from animal studies to hypothesize potential side effects. If a treatmentis a memberof a classof drugs, such as colony-stimulating factors, information regarding side effects occasionally may be generalized from that already known regarding the other drugs
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of the same class. The section on background information in the written protocol provides the rationale for the study and relevant references. These references are the initial starting point for reviewing the literature and developing a theoretical side effect profile. In phase II studies, side effects have already been delineated in the prior phase I studies of the drug and may be the basis for the discussion of the side effects with patient and family members. However, since phase I studies involve only a limited number of patients, caution must be used in labeling side effects as “usual” or “rare” and it is important to explain that in all likelihood, not all the potential side effects for a treatment have been identified. Patient and family education of the research process is also important. The research process includes the goals of the study, differentiating between the phases of study, and special requirements of the study such as randomization. Also included in this discussion is the informed consent process. Although the physician has the ultimate responsibility for obtaining informed consent, the nurse participates in helping the patient understand the consent process, answering questions regarding the protocol, and helping to determine the extent of the patient’s comprehension. The goals of the study should be consistent with the goals of the patient for participating in the study. It has been shown that patients participate in clinical trials for many reasons including to help others by contributing to science, to try all options, and to get the best medical care.6-8 A patient who articulates a goal of cure while enrolling in a phase I study must understand that the purpose of phase I studies is to determine toxicity. Efficacy of the treatment is most often unknown and can only be theorized. Cure is highly unlikely. Indeed, in a retrospective study analyzing complete and partial response rates in phase I studies, Estey et al9 found that only 2% of 1248 patients had a response to treatment. Hence, it is clear that information on the purpose of the study must be clearly explained to patients. lo With this understanding, the patients may still desire to participate and may still hope for cure, but at the very least they understand and accept the trial purpose. Randomization of patients enrolled in phase III trials is also a difficult concept for some patients to accept. In some instances, patients visit a cancer center for the explicit purpose of receiving a treat-
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ment they have read about in the popular literature. If that treatment is only offered within the confines of a clinical trial, the patient may have to partake in the randomization process. The treatment desired may not be the treatment to which they are randomized. This may preclude their willingness to be randomized. Such conflicts and issues must be sorted out in the educational process so that all are committed to the treatment as well as the question addressed in the trial. Thus, it is clear that the educational process is a complex task. Nurses involved in the care of patients at each point in the treatment process must be knowledgeable of the treatment itself and the research process. Education is begun in the ambulatory care clinic by the physician, nurse, clinical nurse specialist, research nurse, and/or chemotherapy nurse. However, each member of the team may have different responsibilities for education depending on the organizational structure of the institution. It is imperative that the nurse understand his or her own beliefs and values regarding clinical trials. i ’ An attitude devaluing clinical trials will be readily conveyed and will have an impact on the commitment that others develop toward clinical research and indeed toward the care of the patient. Direct
Care Giver
The treatment outlined in the clinical trial may be administered in the ambulatory care center12 or in the hospital. Inpatient settings may include the oncology unit, an intensive care unit, clinical research center, or other inpatient units. Regardless of the setting, the nursing care of the patient involves assessment, planning, intervention, and evaluation. Nurses in different roles may have responsibilities of different phases of the nursing process; however, the total process must be performed with care and precision. The research nurse is in a special position to influence the plan for the patient’s nursing care. Consultation with the clinical nurse specialist is valuable in developing a plan for the anticipated side effects that are outside the expertise of the research or staff nurse. Delivering the actual experimental treatment may be the role of the research nurse, staff nurse, or chemotherapy nurse. In any case, the treatment must be delivered according to the protocol. l3 Often others may be involved at the time the treatment is administered, such as pharmacists who are doing
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pharmacokinetic studiesor basic scientists who are collecting blood samplesfor a companion study. A particularly crucial role of the nurse in clinical trials is the determination of toxicities.14 It is the nurses’ observation of the patient after treatment that identifies the side effect profile and will ultimately be the basis for the care plan of patients on the experimental treatment in the future. The documentation of side effects has direct impact on the decision regarding the Maximally Tolerated Dose (MTD) in phase I trials. This is truly a most exciting aspectof participation in clinical trials. Astute observation of each patient and the synthesis of observations across patients is the nature of nursing scholarship in clinical trials. It is the nurse that may be the first to recognize a side effect, perhaps even before the patient is aware of the experience. Delineating a primary nurse to provide care to patients undergoing the sameclinical trial would maximize the opportunity to identify commonalities of patient experiences. As the research nurse or staff nurse is documenting the patient’s responseto treatment, trends in data may become evident and interventions planned to alleviate dose-limiting side effects. Patient Advocate
A primary role of the nurse caring for patients in clinical trials is that of patient advocate.14It has been suggestedthat cancerpatients are particularly vulnerable becauseof their diagnosis and all the implications associated with cancer. l5 Indeed, some patients wish to try anything to treat their disease.Thus it is imperative that such vulnerable patients not be taken advantageof in the clinical trials arena. The informed consentprocess,as discussed by Grady elsewhere in this issue, is designed to ensure that patients’ rights are upheld. Considerable literature has evolved discussing the protection of patients’ rights and the astute researchnurse will be knowledgeable in this area. One aspect of the patient advocate role is to assistpatients in defining their own goals and purposes for participating in a clinical trial. It is important to reaffirm this as the treatment progresses and patients reevaluate their decision to participate. The reevaluation of their original decision may be a source of anxiety for the nurse as she feels that it is crucial that the patient remain on study. Indeed, patients who decide to go off study may hamper the progressof the clinical trial. Yet,
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patients must understand that they may withdraw at any time and suffer no repercussionsfrom the health care team. Patients who begin to give indications that they wish to withdraw require special attention. Such questionsmay be an indication of other underlying problems, such as fatigue, difficulty tolerating the side effects of the treatment, loneliness, or confusion. Initiating discussion with an open mind for the purposeof clarifying the nature of the problem is a helpful, nonthreatening approach. Often such discussionshelp the patient reaffirm the initial reasons for participating and, with assurance that more effective and creative ways of managing the side effects of treatment will be given, the patient may desire to continue treatment. However, for those patients who indeed wish to discontinue treatment. that decision must be honored. Coordinator
Coordination of the protocol and the patients’ carecan be extremely complex. The researchnurse must be familiar with all aspectsof the treatment processand coordinate the care of many different hospital units, including patient care areas, blood bank, pharmacy, laboratory, and outpatient clinic. It is important to note that the attention given patients during this coordination is one of the benefits that patients perceive from participating in clinical trials.’ Their health care is well coordinated and planned. Without clear communication between departments,the patient may receive confusing or contradictory information and health care can become fragmented. In summary, the clinical role of the nurse involved in clinical trials is extensive and complex involving the roles of educator, direct care giver, advocate, and coordinator. The nurse must be interested in the progress of cancer treatment and excited about the opportunity to provide nursing care in situations that are new and ambiguous. Astute powers of observation and synthesis are required. Knowledge of philosophical approachesto treatmentsand reasonswhy patients participate in experimental therapies is essential for the nurse in understanding each patient’s reason for participation. ADMINISTRATIVE
The nurse plays a major role in the administration of the clinical trial. She is a crucial memberof
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the protocol team and is often the individual toward whom all others turn for guidance. Although this may at times be construedastedious, it is most essential, for the data must be valid and consistent for the researchquestion to be answered. Components of the administrative role include the coordination of the patient’s care as well as the coordination of the researchproject. Coordination of the research protocol can be multifaceted. Abdellahi6 lists several areasessential for the effective managementof clinical trials, including definitions of functions and separationof responsibilities, communication structure, welldefined decision making, and identification of goals to measureprogress. The nurse must interact with professionals from many disciplines and is often the first person to be contacted with questions regarding the initiation and progress of the study. It is essential that information be readily available and disseminatedto others. The nurse may also be the first contact of the institution with the public. With clinical alerts now part of the dissemination of research findings by the National Cancer Institute,17 consumers are more aware of treatment options available. They will often call the research nurse for information on the type of clinical trials offered. If the study is a single-institution study, the nurse coordinates planning with the sponsoring agencyand the primary institution. The sponsoring agency may be a drug corporation or a major institution such as the National Cancer Institute. The nurse meets with the team involved in the study and critiques and answers questions about implementation feasibility. Suggestions regarding changes in reporting mechanisms or managing missing data are incorporated into the final document. Knowledge of the primary institution is essential, for if a study is not feasible, it should not be attempted. Data managementmay be an essential part of the role of the research nurse, or it may be delegated to a non-nurse data manager.18The consistent managementof the data allows the study question to be answeredpromptly and efficiently. This involves developing and completing data entry forms, retrieving data from records, and documenting data on appropriate forms. Characteristics of the nurse in performing the administrative role of a clinical trial includes the
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ability to interact comfortably with a variety of professionalsand to organize and implement group meetings. Organization and attention to detail is required to manageand record data forms. Knowledge of reporting mechanismsof toxic side effects and of how eachpiece of data collected impacts on the researchquestion is important. RESEARCH ROLE
The researchrole for the nurse in clinical trials is undergoing change and transition. The purpose of medical researchis to test and evaluate new treatments. The purpose of nursing researchis to evaluate patients’ responsesto treatment or disease. Previously, nurses involved in clinical trials were seenas doing medical research, simply collecting data for physicians. As the role has evolved, no one can doubt the essential component of nursing care delivered to patients and the scholarly advances nurses have made toward the delineation and treatment of symptoms. Indeed, symptom managementis a major component of oncology nursing practice, and nurses involved in clinical trials are key to delineating interventions that are effective. Researchroles that are undertakenby the clinical trials nurse may vary depending on the amountof educationalpreparationof the nurse, the nature of the team involvement, and resources available to the nurse. Fawcett” notes that research activities involve the generation of knowledge, dissemination of knowledge, and utilization of knowledge. The research nurse participates in all three activities in varying degrees. The activities involved in the implementation of the trials are crucial to the generation of knowledge, regarding both medical treatment and nursing care. Data collection offers the opportunity for the nurse to identify trends in the patient experience. Such trends will lead to the scholarly pursuit of analysis and subsequentquestioning the reason for the side effect. Such questions as why patients experienceone side effect and not another or why somepatients seemingly experienceno side effects form interesting researchquestions. At what point during the treatment are the side effects more severe, or perhaps, not more severe, but more distressing? Is the whole experience intolerable or easily tolerable for patients? What are the emotional and financial costs of the treatments?Ques-
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tions such as these arise from the nurse reflecting on the patients’ experience during the data collection and recording process. The nurse in clinical trials research is in the enviable position of providing care for patients experiencing the samedisease and treatment and can identify trends in the patients’ experience. Such examination is termed clinical scholarship and mandates that the nurse document and write about the patients’ experience. Although not a formal researchstudy, such reflections written in a scholarly fashion lead one to greater understanding of the patients’ experience and may becomethe impetus for a formal research study. Formal researchstudies are designedto answera question of relevance to the science of nursing. It is becoming more common for clinical trials researchto have a nursing component or a companion study, as discussedby Ferrell and Cohen elsewhere in this issue. The companion study is usually derived from the primary study but asks a particular nursing question. Quality-of-life research is becoming increasingly applicable to this category. It is appropriate for many studiesto have a quality of life aspect that may come under the realm of nursing. The interest in implementing studies of quality of life evolved as it becamerecognized that sometreatmentsmay prolong life but with a reduction in quality. Alternatively, some treatments, although not improving patient survival, may improve the quality of that survival.*’ Quality-of-life literature is extensive and controversial. The use of tools to measurelife’s quality must be carefully chosen with the endpoint in mind. Dean2’ cautions the use of quality of life as an outcome measure in clinical trials research, identifying the political ramifications of such use. She states that quality-of-life indicators may be used for the purpose of allocating health care resources.To her, this is particularly problematic in view of the questions surrounding quality-of-life research such as the type of measurementsused, the person doing the measurements,and when the measurementsare taken. Despite the problems regarding quality-of-life research, the addition of this component to clinical trials recognizesand affirms that treatmentsare experiencedin the context of one’s life and impact on that quality. Another type of companion study that might prove fruitful is descriptive studies regarding the
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side effects of treatments. Several authors have studied treatment side effects in a descriptive fashion and provide useful models for incorporation into clinical trials. Such studies will provide the basisfor the nursing care should the treatmentgain widespread use. Additionally, companion studies may be designed to evaluate the effectiveness of nursing interventions within particular treatments. The clinical trials involving highly emetic drugs may give rise to companion studies on behavioral interventions to reduce nausea. An alternative to the companion study is one that is totally distinct from the main study, but uses the subjectsenrolled in the clinical trial to answer a nursing question. In this instance, data will be gathered, recorded, and analyzed separately from the main study. Such research may be basic science research or theoretical research. A body of literature that may be fruitful to pursue is the question of motivation for entering clinical trials and for remaining in clinical trials. This requires a nurse as the principle investigator who is separate from the researchteam. Often, the nurse involved in clinical trials is involved in the dissemination of the research findings. Writing researchreports, abstracts,and preparing poster sessionscan be a rewarding finish to a clinical trial in which so much effort has been expended. Presenting papers or being present at poster sessionsenablesthe nurse to answer scientific and clinical questionsregarding the study design, implementation, and analysis. Qualities of the nurse in implementing the researchcomponentof a clinical trial includes ability and easein reading researchreports, understanding the research process, and ability to coordinate a researchprogram. SUMMARY
This article has examined the role of the nurse in clinical trials, particularly the clinical, administrative, and research roles. Components of each role and characteristics essential for the implementation of each role have been examined. The nursing role in clinical trials research is undergoing major transformation from the perception of the nurse as a data collector for medical research to the recognition of the nurse as an essentialmember of the researchteam with a multifaceted role.
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Miaskowski22 identifies two factors influencing the development of oncology nursing practice; scientific and technological advances and societal factors relating to the perception of cancer as a diseaseand changesin the nursing profession. Certainly it is recognizedthat progressin basic science
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researchwill lead to an increasein the complexity and number of clinical trials. Nurses have clearly implemented the roles necessaryto be vital participants and have contributed to answeringquestions leading to improved treatmentsfor the patient with cancer.
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12. Harris TM, Bean C: Changing the role of the nurse in the Hematology-Oncology outpatient setting. Oncol Nurs Forum 18:43-49, 1991 13. Hubbard S: Cancer treatment research: The role of the nurse in clinical trials of cancer therapy. Nurs Clin North Am 17:763-783, 1982 14. Gross J: Clinical research in cancer chemotherapy. Onco1 Nurs Forum 13:59-65, 1986 15. Benoliel JQ: The cancer patient’s right to know and decide: An ethical perspective, in McCorkle R, Hongladarom G (eds): Issues and Topics in Cancer Nursing. Norwalk, CT, Appleton-Century-Crofts, 1986, pp 5-17 16. Abdellah F: Management of clinical trials. J Prof Nurs 6:189, 1990 17. Wittenberg C: Experts debate guidelines for release of research information. J Nat1 Cancer lnst 82:4, 1990 18. White-Hershey D, Nevidjon B: Fundamentals of oncology nurse/data managers-Preparing for a new role. Oncol Nurs Forum 17:371-379, 1990 19. Fawcett J: A typology of nursing research activities according to educational preparation. J Prof Nurs 1:75-78, 1985 20. Vanchieri C: Quality of life gets equal consideration as a clinical trial endpoint. J Nat1 Cancer lnst 82:4, 1990 21, Dean H: Political and ethical implications of using quality of life as an outcome measure. Semin Oncol Nurs 6:303308, 1990 22. Miaskowski C: The future of oncology nursing: A historical perspective. Nurs Clin North Am 25:461-473, 1990
