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BACKGROUND: Since the onset of COVID-19, oncology practices across the US have integrated telemedicine (TM) and remote patient monitoring (RPM) into routine care and clinical trials. The extent of provider experience and comfort with TM/RPM in treatment trials, however, is unknown. We surveyed oncology researchers to assess experience and comfort with TM/RPM. METHODS: Between April 10 and June 1, 2022, we distributed email surveys to US-based members of the American Society of Clinical Oncology (ASCO) whose member records indicated interest or specialization in clinical research. We collected respondent demographic data, clinical trial experience, workplace characteristics, and comfort and experience with TM/RPM use across trial components in phase I and phase II/III trials. TM/RPM was defined as clinical trial-related healthcare and monitoring for patients geographically separated from trial site. RESULTS: There were 141 surveys analyzed (5.1% response rate). Ninety percent of respondents had been Principal Investigators, 98% practiced in a norural site. Most respondents had enrolled patients in phase I (82%) and phase II/III trials (99%). Across all phases and trial components, there was a higher frequency of researcher comfort compared to experience. Regarding remote care in treatment trials, 75% reported using TM, RPM, or both. Among these individuals, 62% had never provided remote care to trial patients before the pandemic. CONCLUSION: COVID-19 spurred the rise of TM/RPM in cancer treatment trials, and some TM/RPM use continues in this context. Among oncology researchers, higher levels of comfort compared with real-world experience with TM/RPM reveal opportunities for expanding TM/RPM policies and guidelines in oncology research.
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COVID-19 , Neoplasias , Telemedicina , Humanos , COVID-19/epidemiologia , Atenção à Saúde , Oncologia , Monitorização Fisiológica , Neoplasias/terapiaRESUMO
This article reviews the implementation challenges to the American Society of Clinical Oncology's ethical framework for including research biopsies in oncology clinical trials. The primary challenges to implementation relate to the definitions of secondary endpoints, the scientific and regulatory framework, and the incentive structure that encourages inclusion of biopsies. Principles of research stewardship require that the clinical trials community correctly articulate the scientific goals of any research biopsies, especially those that are required for the patient to enroll on a trial and receive an investigational agent. Furthermore, it is important to sufficiently justify the characterization of secondary (as distinguished from exploratory) endpoints, protect the interest of research participants, and report accurate and complete information to ClinicalTrials.gov and the published literature.
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In 2013, the Institute of Medicine (IOM) concluded that cancer care in the United States is in crisis. Patients and their families are not receiving the information that they need to make informed decisions about their cancer care. Many patients do not have access to palliative care and too few are referred to hospice at the appropriate point in their disease trajectory. Simultaneously, there is a growing demand for cancer care with increases in new cancer diagnoses and the number of patients surviving cancer. Furthermore, there is a workforce shortage to care for this growing and elderly population. The IOM's report, Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis, outlined recommendations to improve the quality of cancer care. This article provides an overview of the IOM report and highlights the recommendations that are most relevant to practicing clinicians who care for patients with cancer across the continuum. The implementation of the recommendations in clinical practice will require better patient-clinician communication, improved care coordination, targeted clinician training, effective dissemination of evidence-based guidelines and strategies for eliminating waste, and continuous quality assessment and improvement efforts.
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Prática Clínica Baseada em Evidências , Neoplasias/terapia , Assistência Centrada no Paciente , Comunicação , Tomada de Decisões , Humanos , Relações Médico-Paciente , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de SaúdeRESUMO
PURPOSE: The onset of the COVID-19 pandemic created major disruptions in the conduct of cancer clinical trials. In response, regulators and sponsors allowed modifications to traditional trial processes to enable clinical research and care to continue. We systematically evaluated how these mitigation strategies affected data quality and overall trial conduct. METHODS: This study used surveys and live interviews. Forty-one major industry and National Cancer Institute Network groups (sponsors) overseeing anticancer treatment trials open in the United States from January 2015 to May 2022 were invited to participate. Descriptive statistics were used for survey data summaries. Key themes from interviews were identified. RESULTS: Twenty sponsors (48.8%; 15 industry and five Network groups) completed the survey; 11/20 (55.0%) participated in interviews. Sponsors predominantly (n = 12; 60.0%) reported large (≥11 trials) portfolios of phase II and/or phase III trials. The proportion of sponsors reporting a moderate (9) or substantial (8) increase in protocol deviations in the initial pandemic wave versus the pre-pandemic period was 89.5% (17/19); the proportion reporting a substantial increased dropped from 42.1% (n = 8/19) in the initial wave to 15.8% (n = 3/19) thereafter. The most commonly adopted mitigation strategies were remote distribution of oral anticancer therapies (70.0%), remote adverse event monitoring (65.0%), and remote consenting (65.0%). Most respondents (15/18; 83.3%) reported that the pandemic had minimal (n = 14) or no impact (n = 1) on overall data integrity. CONCLUSION: Despite nearly all sponsors observing a temporary increase in protocol deviations, most reported the pandemic had minimal/no impact on overall data integrity. The COVID-19 pandemic accelerated an emerging trend toward greater flexibility in trial conduct, with potential benefits of reduced burden on trial participants and sites and improved patient access to research.
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COVID-19 , Neoplasias , Humanos , COVID-19/epidemiologia , Confiabilidade dos Dados , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , Inquéritos e Questionários , Estados Unidos/epidemiologia , Protocolos de Ensaio Clínico como AssuntoRESUMO
Research biopsies included in cancer clinical trials have the goal of advancing scientific understanding of the biological bases of cancer and its treatments, but may offer no prospect of direct benefit to participants and often pose more than minimal risk. The research community is examining the ethics of research biopsies increasingly often, especially when they are mandatory for study participation but do not support primary study objectives and thus are "nonintegral" to the study. Ethical concerns center on the limited scientific justification supporting some biopsies, risks to research participants, and the potential for coercion and therapeutic misconception during the informed consent process. There is also a lack of comprehensive oversight of research biopsies by regulatory agencies and institutions. This paper reviews these ethical concerns, discusses the scope of federal oversight, and suggests that institutional review boards (IRBs) should assume a larger role in ensuring the ethical conduct of research biopsies. It concludes with guidance to IRBs on how to weigh the risks, benefits, and acceptability of such biopsies in different contexts that is based on a framework the American Society of Clinical Oncology developed for the inclusion of research biopsies in oncology clinical trials.
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Comitês de Ética em Pesquisa , Neoplasias , Biópsia , Humanos , Consentimento Livre e Esclarecido , Oncologia/métodosRESUMO
This manuscript reviews the status of Hispanic/Latinx physicians in oncology, the benefits and challenges to achieving equitable representation, and potential solutions and actions to increase diversity in the oncology workforce. Persons of Hispanic/Latinx origin comprise 18.7% of the population and 16.8% of the adult population in the United States but are only 4.7% of practicing oncologists. The reasons for the lack of representation of Hispanic/Latinx individuals in medicine are multifaceted and include discrimination and biases, exclusionary practices, financial barriers, and lack of role modeling. As a result, patients are deprived the benefits of a representative workforce, such as improved access, enhanced culturally and linguistically competent care, and minimization of health disparities. Solutions included in the manuscript include a description of efforts by ASCO to improve the representativeness of the oncology workforce through its awards programs and educational efforts, especially for Hispanic/Latinx clinicians. The manuscript also outlines individual actions that attending physicians, senior oncologists, oncology leaders, and hospital/cancer center leadership can take to improve the diversity of the oncology workforce and support our Latinx/Hispanic trainees and colleagues. Improving the representativeness of the oncology workforce will require collective action by institutions, medical societies, and individuals. Nevertheless, widespread commitment to creating an inclusive and supported workforce is necessary to ensure the quality of care for minority patients, reduce existing cancer care disparities, and advance innovation in oncology.
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Oncologia , Médicos , Adulto , Institutos de Câncer , Hispânico ou Latino , Humanos , Estados Unidos/epidemiologia , Recursos HumanosRESUMO
PURPOSE: Treatment goals for patients with metastatic cancer include prolongation and maintenance of quality of life. Patients and oncologists have questioned the current paradigm of initial dose selection for systemic therapy; however, data on oncologists' dose selection strategies and beliefs are lacking. METHODS: We conducted an electronic international survey of medical oncologists who treat patients with breast and/or gastrointestinal cancers. Survey questions addressed experiences with, and attitudes toward, dose reduction at initiation (DRI) of a new systemic therapy for patients with metastatic cancer. RESULTS: Among 3,099 eligible oncologists, 367 responded (response rate 12%). Most (52%) reported using DRI at least 10% of the time to minimize toxicities. Gastrointestinal specialists were more likely to report DRI ≥ 10% of the time (72% v 50% of generalists and 51% of breast specialists, P < .005). Of those who dose reduced ≥ 10% of the time, 89% reported discussing potential tradeoffs between efficacy and toxicity with patients. Overall, 65% agreed it is acceptable to lower starting doses to reduce side effects even if it compromises efficacy; younger clinicians were more likely to agree (P < .005). There was strong support (89%) for future trials to determine optimal effective, rather than maximum tolerated, dose. CONCLUSION: Oncology practice varies with regard to discussion and individualized selection of starting doses in the metastatic setting. This study demonstrates a need for consideration of shared decision making regarding initial dose selection and strong support among oncologists for clinical studies to define optimal dosing and best practices for individualizing care.
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Neoplasias , Oncologistas , Humanos , Qualidade de Vida , Oncologia , Neoplasias/tratamento farmacológico , Inquéritos e QuestionáriosRESUMO
This report presents the American Society of Clinical Oncology's (ASCO's) evaluation of the adaptations in care delivery, research operations, and regulatory oversight made in response to the coronavirus pandemic and presents recommendations for moving forward as the pandemic recedes. ASCO organized its recommendations for clinical research around five goals to ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality. The specific goals are: (1) ensure that clinical research is accessible, affordable, and equitable; (2) design more pragmatic and efficient clinical trials; (3) minimize administrative and regulatory burdens on research sites; (4) recruit, retain, and support a well-trained clinical research workforce; and (5) promote appropriate oversight and review of clinical trial conduct and results. Similarly, ASCO also organized its recommendations regarding cancer care delivery around five goals: (1) promote and protect equitable access to high-quality cancer care; (2) support safe delivery of high-quality cancer care; (3) advance policies to ensure oncology providers have sufficient resources to provide high-quality patient care; (4) recognize and address threats to clinician, provider, and patient well-being; and (5) improve patient access to high-quality cancer care via telemedicine. ASCO will work at all levels to advance the recommendations made in this report.
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Pesquisa Biomédica , COVID-19/terapia , Oncologia , Neoplasias/terapia , SARS-CoV-2 , Ensaios Clínicos como Assunto , Atenção à Saúde , Humanos , Projetos de Pesquisa , Sociedades MédicasRESUMO
Pharmacy benefit managers (PBMs) are thoroughly integrated into the drug supply chain as administrators of prescription drug benefits for private insurers, self-insuring business, and government health plans. As the role of PBMs has expanded, their opaque business practices and impact on drug prices have come under increasing scrutiny. PBMs are particularly influential in oncology care because prescription drugs play a major role in the treatment of most cancers and an increasing number of patients with cancer are treated with oral oncology agents managed by PBMs. There is concern that some PBM practices may threaten access to high-quality cancer care and may increase the financial and administrative burden on patients and practices. In this article, we review the role of PBMs in prescription drug coverage and reimbursement, discuss the impact of PBMs on oncology care, and present data from the 2018 ASCO Practice Survey assessing the knowledge and attitude of oncology practices toward PBMs.
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Assistência Farmacêutica , Farmácias , Farmácia , Medicamentos sob Prescrição , Humanos , Seguro de Serviços FarmacêuticosRESUMO
Patients in rural areas face limited access to medical and oncology providers, long travel times, and low recruitment to clinical trials, all of which affect quality of care and health outcomes. Rural counties also have high rates of cancer-related mortality and other negative treatment outcomes. On April 10, 2019, ASCO hosted Closing the Rural Cancer Care Gap, the second event in its State of Cancer Care in America series. The event focused on two aspects of rural cancer care: a review of the major issues and concerns in delivering rural cancer care and a discussion of creative solutions to address rural-nonrural disparities. This article draws from the event and supporting literature to summarize the challenges to delivering high-quality care in rural communities, update ASCO's workforce data on the geographic distribution of oncologists, and highlight 3 institutional approaches to addressing these challenges in diverse rural settings. The experience of the 3 institutions featured in the article suggests that increasing rural patients' access to care requires expanding services and decreasing travel distances, mitigating financial burdens when insurance coverage is limited, opening avenues to clinical trial participation, and creating partnerships between providers and community leaders to address local gaps in care. Because the characteristics of rural communities, health care resources, and patient populations are not homogeneous, rural health disparities require local solutions that are based on community needs, available resources, and trusting and collaborative partnerships.
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Neoplasias , População Rural , Instalações de Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Oncologia , Neoplasias/epidemiologia , Neoplasias/terapia , Recursos HumanosRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has disrupted all aspects of clinical care, including cancer clinical trials. In March 2020, ASCO launched a survey of clinical programs represented on its Cancer Research Committee and Research Community Forum Steering Group and taskforces to learn about the types of changes and challenges that clinical trial programs were experiencing early in the pandemic. There were 32 survey respondents; 14 represented academic programs, and 18 represented community-based programs. Respondents indicated that COVID-19 is leading programs to halt or prioritize screening and/or enrollment for certain clinical trials and cease research-only visits. Most reported conducting remote patient care where possible and remote visits and monitoring with sponsors and/or contract research organizations (CROs); respondents viewed this shift positively. Numerous challenges with conducting clinical trials were reported, including enrollment and protocol adherence difficulties with decreased patient visits, staffing constraints, and limited availability of ancillary services. Interactions with sponsors and CROs about modifying trial procedures were also challenging. The changes in clinical trial procedures identified by the survey could serve as strategies for other programs attempting to maintain their clinical trial portfolios during the COVID-19 pandemic. Additionally, many of the adaptations to trials made during the pandemic provide a long-term opportunity to improve and transform the clinical trial system. Specific improvements could be expanded use of more pragmatic or streamlined trial designs, fewer clinical trial-related patient visits, and minimized sponsor and CRO visits to trial programs.
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Infecções por Coronavirus/epidemiologia , Oncologia , Neoplasias/epidemiologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Betacoronavirus/patogenicidade , COVID-19 , Ensaios Clínicos como Assunto , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Neoplasias/complicações , Neoplasias/terapia , Neoplasias/virologia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Pneumonia Viral/virologia , SARS-CoV-2 , Estados Unidos/epidemiologiaRESUMO
The use of precision medicine and the number of genomic-based treatments and immunotherapies is increasing. Nevertheless, oncology providers face challenges to implementing precision medicine, including in community practices, where most patients receive treatment. On January 31, 2018, ASCO hosted Precision Medicine: Expanding Opportunities, the inaugural event in ASCO's new State of Cancer Care in America (SOCCA) event series. This article draws from the inaugural SOCCA event and the experiences of the SOCCA event participants to summarize the opportunities and challenges of precision medicine, and to highlight three successful models of implementing precision oncology in large, multisite community practices or networks: (1) Intermountain Healthcare, (2) Levine Cancer Institute, Atrium Health, and (3) National Cancer Care Alliance. The experience of these practices suggests that practice innovations that offer clinical decision support through molecular tumor boards and clinical pathways, and administrative support for prior authorization and clinical trial matching are key to successful implementation of large-scale, community-based precision medicine programs.
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Serviços de Saúde Comunitária/normas , Sistemas de Apoio a Decisões Clínicas , Atenção à Saúde/normas , Genômica/métodos , Implementação de Plano de Saúde , Neoplasias/terapia , Medicina de Precisão , Humanos , Imunoterapia , Neoplasias/genética , Guias de Prática Clínica como Assunto/normasRESUMO
In contrast to clinical biopsies, where tissue is collected to inform patient care, research biopsies are performed for scientific purposes to potentially enhance understanding of the biologic bases of cancer and drug action, thereby improving diagnosis and treatment, but they may offer no direct benefit to participants and have known risks. The widespread use of research biopsies that do not have the potential to directly benefit participants has come under scrutiny, with critics raising ethical concerns related to the adequacy of participant protections, informed consent, and participant understanding of the risks and benefits, as well as the scientific impact of research biopsies on drug development and treatment. This manuscript presents the American Society of Clinical Oncology's (ASCO's) ethical framework for incorporation of research biopsies in trials. The framework provides guidance on the circumstances to include optional and mandatory biopsies, as well as provides recommendations to stakeholders on necessary steps for improving the conduct of research biopsies overall.
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Biópsia/ética , Ensaios Clínicos como Assunto/ética , Oncologia/ética , Neoplasias/diagnóstico , Neoplasias/terapia , Biomarcadores Tumorais/análise , Biópsia/efeitos adversos , Humanos , Consentimento Livre e Esclarecido/ética , Oncologia/métodos , Neoplasias/patologia , Guias de Prática Clínica como AssuntoRESUMO
PURPOSE: To develop recommendations for clinical trial reporting that address the unique efficacy, toxicity, and combination and sequencing aspects of immuno-oncology (IO) treatments. METHODS: ASCO and the Society for Immunotherapy of Cancer (SITC) convened a working group that consisted of practicing medical oncologists, immunologists, clinical researchers, biostatisticians, and representatives from industry and government to develop Trial Reporting in Immuno-Oncology (TRIO) recommendations. These recommendations are based on expert consensus, given that existing data to support evidence-based recommendations are limited. CONCLUSION: The TRIO recommendations are intended to improve the reporting of IO clinical trials and thus provide more complete evidence on the relative benefits and risks of an IO therapeutic approach. Given the rapid expansion of the number of IO clinical trials and ongoing improvements to the evidence base supporting the use of IO treatments in clinical care, these recommendations will likely need regular revision as the IO field develops.
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Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Imunoterapia/métodos , Imunoterapia/normas , Prontuários Médicos/normas , Neoplasias/terapia , Consenso , Humanos , Neoplasias/imunologiaRESUMO
PURPOSE: Investigators often send reports to sponsors that incorrectly categorize adverse event (AE)s as serious or attribute AEs to investigational drugs. Such errors can contribute to high volumes of uninformative investigational new drug safety reports that sponsors submit to the US Food and Drug Administration and participating investigators, which strain resources and impede the detection of valid safety signals. To improve the quality of serious AE (SAE) reporting by physician-investigators and research staff, ASCO developed and tested a Decision Aid. METHODS: A preliminary study with crossover design was conducted in a convenience sample. Physician-investigators and research staff were randomly assigned to receive case studies. Case studies were assessed for seriousness and attribution, first unassisted and then with the Decision Aid. Participants completed a feedback survey about the Decision Aid. Effectiveness of reporting and attribution are reported as odds ratios (ORs) with 95% CI. Power to detect associations was limited because of a small sample size. RESULTS: The Decision Aid did not significantly affect accuracy of determining seriousness (OR, 0.87; 95% CI, 0.31 to 2.46), but it did significantly increase accuracy of attributing an SAE to a drug (OR, 3.60; 95% CI, 1.15 to 11.4). Most of the 29 participants reported that the Decision Aid was helpful (93%) and improved decision-making time (69%) and confidence in reporting (83%), and that they would use the Decision Aid in practice (83%). CONCLUSION: The Decision Aid shows promise as a method to improve the quality of SAE attribution, which may improve the detection of valid safety signals and reduce the administrative burden of uninformative investigational new drug safety reports. Study of the Decision Aid in a larger sample with analysis stratified by participant role and SAE reporting experience would further assess the tool's impact.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Técnicas de Apoio para a Decisão , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Drogas em Investigação/efeitos adversos , Drogas em Investigação/uso terapêutico , Humanos , Neoplasias/epidemiologia , Neoplasias/patologia , Pesquisadores , Estados Unidos/epidemiologia , United States Food and Drug AdministrationRESUMO
As part of the ongoing efforts to address the lack of clinical research on older adults with cancer, the American Society of Clinical Oncology (ASCO) and the US Food and Drug Administration cosponsored a public workshop on geriatric oncology in November 2017. The goals were to review progress, build collaborations across stakeholders, and generate new action items for increasing the evidence base for treating older adults with cancer. It built on previous work of the Institute of Medicine, ASCO, and the U13 Conferences convened by the Cancer and Aging Research Group, the National Cancer Institute, and the National Institute of Aging between 2010 and 2015. The workshop drew a diverse group of presenters, panelists, and attendees, including academic and clinical oncologists, regulators, other government officials, representatives from industry, and patient advocacy groups. Attendees at the workshop were tasked with proposing next steps to address the lack of evidence on treating older adults with cancer. Based on the workshop discussions, four new action items to move the field forward were developed: 1) increase enrollment of older adults in clinical trials, 2) collect more information on older adults enrolled on clinical trials, 3) expand the use of real-world data in research on older adults, and 4) strengthen collaboration between stakeholders to develop advocacy and policy solutions. These action items, alongside the previous ASCO, Institute of Medicine, and U13 recommendations, provide a strategy for improving the evidence base for treating older adults with cancer and ensuring all patients with cancer receive high-quality, evidence-based care.
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Medicina Baseada em Evidências , Avaliação Geriátrica , Oncologia , Neoplasias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normas , Humanos , Oncologia/métodos , Oncologia/normas , Estados Unidos , United States Food and Drug AdministrationRESUMO
PURPOSE: To develop recommendations for clinical trial reporting that address the unique efficacy, toxicity, and combination and sequencing aspects of immuno-oncology (IO) treatments. METHODS: ASCO and the Society for Immunotherapy of Cancer (SITC) convened a working group that consisted of practicing medical oncologists, immunologists, clinical researchers, biostatisticians, and representatives from industry and government to develop Trial Reporting in Immuno-Oncology (TRIO) recommendations. These recommendations are based on expert consensus, given that existing data to support evidence-based recommendations are limited. CONCLUSION: The TRIO recommendations are intended to improve the reporting of IO clinical trials and thus provide more complete evidence on the relative benefits and risks of an IO therapeutic approach. Given the rapid expansion of the number of IO clinical trials and ongoing improvements to the evidence base supporting the use of IO treatments in clinical care, these recommendations will likely need regular revision as the IO field develops.
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Ensaios Clínicos como Assunto/normas , Imunoterapia , Neoplasias/tratamento farmacológico , Projetos de Pesquisa/normas , Protocolos de Quimioterapia Combinada Antineoplásica , Consenso , Progressão da Doença , Humanos , Imunoterapia/efeitos adversos , Oncologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: This analysis evaluates the impact of bundling drug costs into a hypothetic bundled payment. METHODS: An economic model was created for patient vignettes from: advanced-stage III colon cancer and metastatic non-small-cell lung cancer. First quarter 2016 Medicare reimbursement rates were used to calculate the average fee-for-service (FFS) reimbursement for these vignettes. The probabilistic risk faced by practices was captured by the type of patients seen in practices and randomly assigned in a Monte Carlo simulation on the basis of the given distribution of patient types within each cancer. Simulations were replicated 1,000 times. The impact of bundled payments that include drug costs for various practice sizes and cancer types was quantified as the probability of incurring a loss at four magnitudes: any loss, > 10%, > 20%, or > 30%. A loss was defined as receiving revenue from the bundle that was less than what the practice would have received under FFS; the probability of loss was calculated on the basis of the number of times a practice reported a loss among the 1,000 simulations. RESULTS: Practices that treat a substantial proportion of patients with complex disease compared with the average patient in the bundle would have revenue well below that expected from FFS. Practices that treat a disproportionate share of patients with less complex disease, as compared with the average patient in the bundle, would have revenue well above the revenue under FFS. Overall, bundled payments put practices at greater risk than FFS because their patient case mix could greatly skew financial performance. CONCLUSION: Including drug costs in a bundle is subject to the uncontrollable probabilistic risk of patient case mixes.