The International Conference on Malignant Bowel Obstruction: A Meeting of the Minds to Advance Palliative Care Research

Abstract

There is a dearth of well-designed clinical research focusing on palliative care in cancer patients, especially those who are near the end of life. Reasons for this include ethical dilemmas in conducting such trials, communication barriers between specialties, and unclear standards for best care practices. To ensure that patients with incurable illnesses are offered the best available care, it is essential to develop and disseminate research methodologies well suited to this population. Given the multidimensional and culture-dependent nature of the end-of-life experience, it is necessary to adopt an interdisciplinary approach to developing research methods. As a means of initiating the process of palliative clinical research methodology development, malignant bowel obstruction (MBO) was used as a model to develop a research protocol. Although many treatment options for MBO have been proposed, existing literature offers little guidance with regard to algorithms for optimal management. To this end, an interdisciplinary summit of international leaders in quality-of-life research, ethno-cultural variability, palliative medicine, surgical oncology, gastroenterology, major consortium research, medical ethics, and patient advocacy/cancer survivors was convened in Pasadena, California, on November 12-13, 2004. Participants also represented the broad ethnic and racial perspectives required to develop culturally sensitive research methods. Consensus on methodological approaches was attained through vigorous debate. Using the conference-developed MBO model to implement trials will advance palliative care research.

The Need for Palliative Care Research

Supportive and palliative care has been recognized as an important component of quality care for all cancer patients, particularly for those with advanced or incurable disease (1-3). Given an estimated 1,372,910 new patients diagnosed with cancer in the United States in 2005 (excluding non-melanoma skin cancers), and approximately 570,280 cancer related deaths (4), care for those patients who are near the end of life is an essential aspect of cancer care (5).

Palliative care is an interdisciplinary team approach to care with a focus on comfort and quality of life rather than prolongation of life or “cure” for a patient and their loved ones. Although many treatments currently exist to manage symptoms and complications of advanced cancer, there continues to be a paucity of well-designed prospective clinical trials examining state-of-the-art practices, impeding the further development of evidence-based guidelines. The absence of an established evidence base in many areas of palliative care is at least due in part to major challenges investigators face in designing palliative care trials. Research challenges include ethical issues in conducting such trials, barriers to collaborative research across specialties, and unclear standards for the types of “best care” practices that should be employed as part of such trials (6,7). Consequently, the young specialty of palliative medicine is struggling to develop an evidence base commensurate with that of other specialties, threatening its credibility within the academic arena. In other words, as stated by Casarett, “As long as the randomized controlled trial is the standard by which effectiveness is judged, the field whose interventions have not been proven by this test is at risk of being relegated to second-class status in the medical hierarchy”(8).

In the absence of a firm evidence-based foundation for clinical practice, care for patients with incurable cancer is frequently based on anecdotal evidence and provider experience. Some treatment opportunities may be delayed or never considered at all, and other non-beneficial and burdensome interventions may be instituted. Regardless of whether the resulting bias is one of over- or under-treatment, optimal care of patients with advanced illness requires a commitment to base treatment approaches on scientific fact rather than anecdotal experience. The National Cancer Policy Board recently agreed to this viewpoint, noting that research addressing the needs of patients with incurable cancers is severely deficient (1). Increasing research for this population, however, requires more complete description of the specific methodologic and ethical barriers in the realms of palliative and end-of-life care, as well as expert consensus on approaches to developing research strategies and design.

Dilemmas and Barriers to Palliative Care Research

Palliative care researchers must confront distinctive ethical dilemmas and barriers that extend far beyond those of standard research trials (9). While ethical issues are not unique to patients facing life's end, they are often magnified in this population and compound the potential ethical issues present in all clinical research trials. These include the vulnerability of the population from which study subjects are recruited, high rates of mental incapacity and emotional distress creating challenges to informed consent, addressing conflicts of interest within the dual roles of the clinician-researcher, the invasiveness and increased frequency of testing relative to standard clinical practice, and questions of scientific value which must balance the benefits and burdens of unproven interventions in a population in whom comfort may be a priority. Ethical concerns specific to palliative research include the difficulty in assessing the risks and benefits of research participation; randomization, especially if there is a “no treatment arm”; and the unstable mental status of patients, with difficulty assessing capacity. Methodological challenges include high rates of loss to follow-up due to physical and mental incapacity and death, the biases introduced by the need for surrogate respondents, and the difficulty of determining appropriate outcomes and methods for assessing those outcomes. Within palliative surgery and other invasive specialty areas, specific concerns include the risks of major morbidity and mortality these treatment approaches entail; patient loss of decision-making capacity and management of life-threatening emergencies in the peri-procedure period; difficulty with equipoise (10) when faced with vastly different treatment options (surgical versus non-surgical); and the “all-or-nothing” nature of surgery, making irrelevant the idea that a patient should be free to withdraw from a study at any time.

Despite the challenges alluded to above, the effectiveness of palliative interventions must nevertheless be assessed with the same rigor that is employed in assessing other medical interventions. As with all treatments of uncertain benefit, we must “overcome ethical objections to research and ingrained beliefs in established treatments”(11). While palliative surgery poses some unique dilemmas within the larger scope of palliative care research, even these barriers can usually be overcome with well-constructed studies carried out by thoughtful research teams (12,13). Indeed, the methodological difficulties in palliative care research are all surmountable through existing techniques and appropriately careful scientific design (14). Communication that these hurdles can be surmounted remains a barrier to the implementation in palliative care settings.

In addition to the challenges described above, designing palliative care research with methodologic precision must account for the diversity of ethnic, cultural, and religious backgrounds that patients bring with them into their experience of life-limiting illness. A patient's experience of illness is both multidimensional -- incorporating physical, emotional, social, and spiritual dimensions -- and culture-dependent, in that the experience is shaped in large part by the cultural milieu in which the patient resides. Researchers have identified deficiencies in the access of racial and ethnic minorities to palliative care services (15), suggesting important opportunities for palliative care research to identify the unique perspectives and service needs of culturally diverse populations.

Opportunities for Palliative Care Research

The dearth of high-quality clinical research in palliative care relative to other, non-palliative clinical conditions (16) suggests a clear opportunity to advance the science, and improve the quality of care, for patients afflicted with cancer. At the same time, those interested in pursuing palliative care research could benefit from expert assistance in developing methods for the conduct of palliative care trials that will maximize the chance for trial results to be valid, safe, and ethical. Without such advancements in research methods, policies, and procedures, the field of palliative care risks a future where clinical practices are ill informed, where research may be suboptimally conducted, and ultimately, where patients will suffer less than optimal care.

Since the goal of the NCI, as outlined by the Director Andrew C. von Eschenbach, MD, is to relieve suffering and death related to cancer by 2015, it implies an imperative to address immediately the needs of those patients suffering from the effects of cancer or its treatment. To ensure that these patients receive the best possible care, we must determine the optimal treatment regimens. As with all cancer therapies, the gold standard continues to be the randomized prospective clinical trial. This goal has admirably been pursued with regard to cancer trials, which focus on cure; it is urgently needed in the palliative care of patients with advanced cancer and terminal disease.

Malignant Bowel Obstruction as a Model for Palliative Care Research

In choosing a clinical problem as a model for palliative care research, there are several criteria that must be fulfilled. First, the problem must be reasonably common, at least related to patients with advanced disease. Second, the problem and its treatment should have clear implications on the patient's quality of life. Next, there must be a clear clinical dilemma regarding the best treatment approach. There must be clear diverse approaches to therapy. Treatments may be quite dissimilar, as with use of medications versus more invasive approaches. Finally, there must be equipoise for those that care for patients with this clinical problem. While there may be bias related to which treatment is optimal, it is necessary that practitioners are able to concede that an alternative approach could be optimal. Conference organizers (Table 1) selected MBO as a target condition that fulfilled these criteria. It is a relatively common complication of advanced solid tumors (17-20), and causes significant morbidity and mortality.

Table 1.

Conference Planning Committee

Name	Affiliation	Role
Robert S. Krouse, MD	University of Arizona/Southern Arizona Veterans Affairs Health Care System	Conference Organizer and Moderator
Ira Byock, MD	Dartmouth-Hitchcock Medical Center	Leader, Implementation Group
David Casarett, MD, MA	University of Pennsylvania/Philadelphia VAMC	Leader, Ethics Group
Marcia Grant, DNSc, RN	City of Hope National Medical Center/Beckman Research Institute	Leader, Cross-Cultural Group
Kenneth Rosenfeld, MD	UCLA/Greater Los Angeles Healthcare System	Leader, Outcomes Group
Jeff Sloan, PhD	Mayo Clinic, Rochester	Leader, Outcomes Group

Malignant bowel obstruction is the blockage of the small or large intestine in a patient with advanced cancer. Most practitioners feel that the obstruction must be due to tumor, although there is some debate about this definition. Since MBO usually occurs in the context of peritoneal carcinomatosis, it is relatively more common in cancers with a propensity for this form of dissemination. Cancers in this category include most gastrointestinal and gynecologic malignancies. More rarely, malignancies from other sites, including lung, breast, and melanoma, can also result in MBO.

Therapy directed at MBO must achieve palliative goals, such as allowing the patient to go home, restoration of ability to eat, relieving distension, curtailing nausea and vomiting, and most generally, improving quality of life. A wide range of treatment options currently exist for MBO, including surgical, endoscopic, and medical approaches, without a single dominant standard of care. Although invasive management approaches are often considered in patients who may regain an acceptable quality of life for at least a period of time, decision-making remains complex and must account for a wide range of patient and caregiver preferences and significant variation in cross-cultural values, attitudes and preferences towards end-of-life care. In addition, in cases of MBO, there is often substantial uncertainty associated both with the risks of surgical intervention in an individual patient, as well as a patient's survival expectancy with or without surgery.

Unfortunately, the quality and quantity of literature available to guide therapy for MBO is less than optimal. Most articles are the result of retrospective studies and emanate from single, tertiary care institutions, reporting an experience with a selected population of patients with MBO over many years. The few prospective studies that have been reported have most often been uncontrolled observational studies, assessing the outcome with a single form of therapy. Given the paucity of evidence to guide therapy, physicians are forced to base therapeutic decision-making on individual experience. This paradigm leads to tremendous variation in treatment and outcome. Although this problem is not unique to palliative care, the stakes for clinicians and their patients are arguably greater. Treatment based on individual experience may lead to unwarranted therapeutic nihilism or zealousness depending on the practitioner, in some cases resulting in withholding of quality-of-life improving therapy, while in others, embarking on non-beneficial and potentially morbid treatment.

Improving the quality and consistency of care for patients with MBO will require carefully designed clinical trials. Only in this way can clinical practices designed to maximize palliation of MBO be rationally applied for the benefit of these individuals in the terminal stages of life. This line of reasoning and the desire to begin to build a clinical evidence base to rationally guide therapeutic decision-making in palliative care resulted in the international collaborative conference focused on MBO.

Conference Objectives and Structure

In response to the current deficiencies in clinical palliative care research, on November 12-13, 2004, an international consensus conference was convened in Pasadena, California to address methodologic issues in this area. The primary goal of the conference was to develop a “road map” for meeting the challenges of developing a palliative care evidence base, and to specifically address the following objectives:

1) use the clinical dilemma of malignant bowel obstruction (MBO) as a model to explore clinical, research, ethical, and cultural barriers to prospective studies of patients with advanced cancer,

2) develop an integrated methodological framework for the implementation of prospective randomized studies of patients with advanced cancer,

3) apply integrative palliative care research methods and an implementation framework to a prospective randomized trial for patients with malignant bowel obstruction, and

4) disseminate methodologies and implementation strategies for use by researchers and clinicians working with patients who have advanced cancer.

Experts in the fields of palliative medicine, quality of life research, statistics, medical, surgical, and gynecologic oncology, gastroenterology, intercultural issues, and patient advocacy participated in this conference (Table 2). While there are many notable figures in these fields who could have also been included at this conference, we decided to keep the group small so that each person and each field could be represented and heard. In all, the meeting participants were a well-rounded and active group that engaged in the various issues towards a common goal: the implementation of RCTs in the population of patients facing the end of life due to cancer.

Table 2.

Conference Participants

Name	Affiliation	Role
Peter Angelos, MD, PhD	Northwestern University	Participant
Thomas Anthony, MD	North Texas VA	Participant
Todd Baron, MD	Mayo Clinic, Rochester	Participant/Presenter
David Cella, PhD	Northwestern University	Participant
Dennis S. Chi, MD, FACOG	Memorial Sloan-Kettering Cancer Center	Participant
Stephen Connor, PhD	National Hospice and Palliative Care Organization	Participant
Stephen Joel Coons, PhD	University of Arizona	Participant
John Cunningham, MD	University of Arizona	Participant
Amylou Dueck	Mayo Clinic-Rochester	Assistant/Recorder
Geoffrey Dunn, MD	Great Lakes Hospice	Participant
Betty Ferrell, PhD	City of Hope National Medical Center	Participant
David Feuer, MD	National Health Service, London UK	Participant/Presenter
Iris Cohen Fineberg, PhD, MSW	UCLA	Assistant/Recorder
Patricia Ganz, MD	UCLA	Participant
Dava Gerard, MD, MPH	Harrington Cancer Center	Assistant/Recorder
Sylvan Green, MD	Arizona Cancer Center/Univ. of Arizona	Participant/Presenter
Anne Herbst, MD	University of Arizona	Assistant/Recorder
Marjorie Kagawa-Singer, PhD	UCLA	Participant
Martin Karpeh, MD	Stony Brook	Participant
Barry M. Kinzbrunner, MD	VITAS Healthcare Corp.	Participant
Ann Kolker	Ovarian Cancer National Alliance	Participant
Jean Kutner, MD	University of Colorado	Participant
Alice Laneader-Seeger, CIP	University of Pennsylvania	Assistant/Recorder
Joseph Lipscomb, PhD	Emory University	Participant
Sebastiano Mercadante, MD	La Maddalena, Palermo, Italy	Participant/Presenter
Thomas Miner, MD	Brown University	Participant
Tom Mosich	American Cancer Society Volunteer	Participant
Richard Mularski, MD	UCLA	Assistant/Recorder
Geraldine Padilla, PhD	Univ. California San Francisco	Participant
Guadalupe Palos, RN, LMSW, DrPH	MD Anderson Cancer Center	Participant
Richard Payne, MD	Duke University	Participant
Susan Shinagawa	Asian American Network for Cancer	Participant
Pauline Sieverding, PhD, JD, MPA	Veterans Affairs HSR'D	Participant
Elizabeth Smart	National Coalition for Cancer Survivorship	Participant
Ellen Stovall	National Coalition for Cancer Survivorship	Participant
Julie Swaney, MDiv	University of Colorado Health Sciences Ctr	Participant
Lawrence Wagman, MD	City of Hope National Medical Center	Participant
Giles Whalen, MD	University of Massachusetts	Participant

The forum was structured with as series of short talks in the morning of Day 1 related to palliative care research and MBO to refresh all participants related to the conference objectives and opportunities. The afternoon of Day 1 were breakout sessions related to major concerns for initiating a palliative care trial (Outcome Measures; Ethical Dilemmas, Barriers, and Solutions in Palliative Care Research; Cross-cultural Issues in Palliative Care Research; Palliative Care Study Implementation), as well as the design of a potential MBO trial. Vibrant debate was noted in each group, and assistants took careful notes during these sessions. On Day 2, findings of each group were reviewed, and an attempt was made to “flesh-out” what an MBO trial may look like. Points of agreement and persistent disagreement were noted.

Goals of Supplement

This supplement addresses the major goal to disseminate conference findings to researchers and clinicians who care for those facing the end of life. It reviews issues, conclusions, and ongoing dilemmas of each breakout session subgroup of the meeting. Based on the consensus findings of this meeting, conference organizers hope to provide guidance to prospective palliative care researchers, which ultimately should advance scientific knowledge in the care of patients near the end of life. Once clear guidelines for palliative care trials are available, the possible research questions and studies are unlimited. This will ultimately place palliative research and care on the same level as those directed at a cure for patients with cancer.