Palliative Care for Patients With Cancer: ASCO Guideline Update.

PURPOSE: To provide evidence-based guidance to oncology clinicians, patients, nonprofessional caregivers, and palliative care clinicians to update the 2016 ASCO guideline on the integration of palliative care into standard oncology for all patients diagnosed with cancer. METHODS: ASCO convened an Expert Panel of medical, radiation, hematology-oncology, oncology nursing, palliative care, social work, ethics, advocacy, and psycho-oncology experts. The Panel conducted a literature search, including systematic reviews, meta-analyses, and randomized controlled trials published from 2015-2023. Outcomes of interest included quality of life (QOL), patient satisfaction, physical and psychological symptoms, survival, and caregiver burden. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 52 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS: Evidence-based recommendations address the integration of palliative care in oncology. Oncology clinicians should refer patients with advanced solid tumors and hematologic malignancies to specialized interdisciplinary palliative care teams that provide outpatient and inpatient care beginning early in the course of the disease, alongside active treatment of their cancer. For patients with cancer with unaddressed physical, psychosocial, or spiritual distress, cancer care programs should provide dedicated specialist palliative care services complementing existing or emerging supportive care interventions. Oncology clinicians from across the interdisciplinary cancer care team may refer the caregivers (eg, family, chosen family, and friends) of patients with cancer to palliative care teams for additional support. The Expert Panel suggests early palliative care involvement, especially for patients with uncontrolled symptoms and QOL concerns. Clinicians caring for patients with solid tumors on phase I cancer trials may also refer them to specialist palliative care.Additional information is available at www.asco.org/supportive-care-guidelines.

Patient partnership in cardiovascular clinical trials.

Patients are ultimately the end-users of medical therapies and need to be actively integrated as contributors and decision-makers in the process of product development throughout product lifecycles. This is increasingly being recognized by patients, investigators, regulators, payers, sponsors, and medical journals. However, cardiovascular research remains behind other fields in terms of the extent of patient involvement and awareness of clinical trials in cardiovascular research. True patient partnerships in cardiovascular therapeutic development may permit more rapid recognition of unmet needs, ensure alignment of product development priorities with patient priorities, improve efficiency of trials (e.g. recruitment), and ensure outcomes of value to patients are being measured in trials (e.g. quality of life). This paper reviews ongoing initiatives and remaining opportunities to accomplish contributive patient involvement in cardiovascular clinical research.

Pragmatic patient engagement in designing pragmatic oncology clinical trials.

Oncology trials are the cornerstone of effective and safe therapeutic discoveries. However, there is increasing demand for pragmatism and patient engagement in the design, implementation and dissemination of oncology trials. Many researchers are uncertain about making trials more practical and even less knowledgeable about how to meaningfully engage patients without compromising scientific rigor to meet regulatory requirements. The present work provides practical guidance for addressing both pragmaticism and meaningful patient engagement. Applying evidence-based approaches like PRECIS-2-tool and the 10-Step Engagement Framework offer practical guidance to make future trials in oncology truly pragmatic and patient-centered. Consequently, such patient-centered trials have improved participation, faster recruitment and greater retention, and uptake of innovative technologies in community-based care.

Randomized, Double-Blind Trial on the Impact of Word Count in Cancer Clinical Trial Consent Forms.

PURPOSE: This randomized, double-blind study sought to understand whether cancer clinical trial consent form verbosity detracts from patients' decision making on trial enrollment. METHODS: This trial tested mock consent forms of 2,000, 4,000, and 6,000 words. The first two comprised the two experimental arms and the third the control arm. Phase II was conducted to identify the promising arm, which, in phase III, was compared with the control arm. Each consent form described the same trial. Eligible adult patients reported a cancer history and English literacy. The primary end point used a patient-reported Likert scale to assess the relationship between information in the consent form and trial decision making. RESULTS: In phase II, 93 patients were accrued and prompted the selection of the 2,000-word consent form for phase III. In phase III, 182 patients were recruited, resulting in 240 total evaluable patients to compare the 2,000-word versus the 6,000-word arm (control). For the primary end point, 103 (84%) and 107 (91%) patients in the 2,000- and 6,000-word arms, respectively, strongly agreed or agreed with the following: "The information in this consent form helped me make a decision about whether or not to enroll in the trial" (two-sided, P = .14). Median time to read each consent form was 8 and 12 minutes, respectively (two-sided, P < .0001). Among those assigned these consent forms, 84% and 73%, respectively (two-sided, P = .04) signed or expressed a willingness to sign. CONCLUSION: This study's primary end point was not met. However, secondary outcomes suggest a need to further study the efficiency and efficacy of shorter consent forms for cancer clinical trial enrollment.

Understanding and Overcoming the Challenges Related to Cardiovascular Trials Involving Patients with Kidney Disease.

Cardiovascular disease is a prevalent and prognostically important comorbidity among patients with kidney disease, and individuals with kidney disease make up a sizeable proportion (30%-60%) of patients with cardiovascular disease. However, several systematic reviews of cardiovascular trials have observed that patients with kidney disease, particularly those with advanced kidney disease, are often excluded from trial participation. Thus, currently available trial data for cardiovascular interventions in patients with kidney disease may be insufficient to make recommendations on the optimal approach for many therapies. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration, convened a multidisciplinary, international work group and hosted a stakeholder workshop intended to understand and develop strategies for overcoming the challenges with involving patients with kidney disease in cardiovascular clinical trials, with a particular focus on those with advanced disease. These efforts considered perspectives from stakeholders, including academia, industry, contract research organizations, regulatory agencies, patients, and care partners. This article outlines the key challenges and potential solutions discussed during the workshop centered on the following areas for improvement: building the business case, re-examining study design and implementation, and changing the clinical trial culture in nephrology. Regulatory and financial incentives could serve to mitigate financial concerns with involving patients with kidney disease in cardiovascular trials. Concerns that their inclusion could affect efficacy or safety results could be addressed through thoughtful approaches to study design and risk mitigation strategies. Finally, there is a need for closer collaboration between nephrologists and cardiologists and systemic change within the nephrology community such that participation of patients with kidney disease in clinical trials is prioritized. Ultimately, greater participation of patients with kidney disease in cardiovascular trials will help build the evidence base to guide optimal management of cardiovascular disease for this population.

Implications of response shift for micro-, meso-, and macro-level healthcare decision-making using results of patient-reported outcome measures.

PURPOSE: Results of patient-reported outcome measures (PROMs) are increasingly used to inform healthcare decision-making. Research has shown that response shift can impact PROM results. As part of an international collaboration, our goal is to provide a framework regarding the implications of response shift at the level of patient care (micro), healthcare institute (meso), and healthcare policy (macro). METHODS: Empirical evidence of response shift that can influence patients' self-reported health and preferences provided the foundation for development of the framework. Measurement validity theory, hermeneutic philosophy, and micro-, meso-, and macro-level healthcare decision-making informed our theoretical analysis. RESULTS: At the micro-level, patients' self-reported health needs to be interpreted via dialogue with the clinician to avoid misinterpretation of PROM data due to response shift. It is also important to consider the potential impact of response shift on study results, when these are used to support decisions. At the meso-level, individual-level data should be examined for response shift before aggregating PROM data for decision-making related to quality improvement, performance monitoring, and accreditation. At the macro-level, critical reflection on the conceptualization of health is required to know whether response shift needs to be controlled for when PROM data are used to inform healthcare coverage. CONCLUSION: Given empirical evidence of response shift, there is a critical need for guidelines and knowledge translation to avoid potential misinterpretations of PROM results and consequential biases in decision-making. Our framework with guiding questions provides a structure for developing strategies to address potential impacts of response shift at micro-, meso-, and macro-levels.

Challenges and Potential Improvements to Patient Access to Pharmaceuticals: Examples From Cardiology.

Patient access to a drug after US regulatory approval is controlled by complex interactions between governmental and third-party payers, pharmacy benefit managers, distributers, manufacturers, health systems, and pharmacies that together mediate the receipt of goods by patients after prescription by clinicians. Recent medication approvals highlight why and how the distribution of clinically beneficial novel therapies is controlled. Although imposed limitations on availability may be rational considering the fiduciary responsibilities of payers and escalating spending on health care and pharmaceuticals, transparency and communication are lacking, and some utilization management may disproportionately affect vulnerable populations. Analysis of the current health insurance landscape suggests mechanisms by which patient access to appropriate medications can be improved and patient and clinician frustration reduced while acknowledging the financial realities of the pharmaceutical marketplace. We propose creation of a shared, standardized, and transparent process for coverage decisions that minimizes administrative barriers and is defensible on the basis of clinical and cost-effectiveness evidence. These reforms would benefit patients and improve the efficiency of the pharmaceutical system.

Improving the Design of Future PCI Trials for Stable Coronary Artery Disease: JACC State-of-the-Art Review.

The role of percutaneous coronary interventions in addition to medical therapy for patients with stable coronary artery disease continues to be debated in routine clinical practice, despite more than 2 decades of randomized controlled trials. The residual uncertainty arises from particular challenges facing revascularization trials. Which endpoint do doctors care about, and which do patients care about? Which participants should be enrolled? What background medical therapy should we use? When is placebo control relevant? In this paper, we discuss how these questions can be approached and examine the merits and disadvantages of possible options. Engaging multiple stakeholders, including patients, researchers, regulators, and funders, to ensure the design elements are methodologically valid and clinically meaningful should be an aspirational goal in the development of future trials.

Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update.

PURPOSE: To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors. METHODS: An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS: The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update. RECOMMENDATIONS: The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.Additional information is available at www.asco.org/survivorship-guidelines.

Advancing Research on the Complex Interrelations Between Atrial Fibrillation and Heart Failure: A Report From a US National Heart, Lung, and Blood Institute Virtual Workshop.

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.

Eligibility and Radiologic Assessment for Adjuvant Clinical Trials in Kidney Cancer.

PURPOSE: To harmonize the eligibility criteria and radiologic disease assessment definitions in clinical trials of adjuvant therapy for renal cell carcinoma (RCC). METHOD: On November 28, 2017, US-based experts in RCC clinical trials, including medical oncologists, urologic oncologists, regulators, biostatisticians, radiologists, and patient advocates, convened at a public workshop to discuss eligibility for trial entry and radiologic criteria for assessing disease recurrence in adjuvant trials in RCC. Multiple virtual meetings were conducted to address the issues identified at the workshop. RESULTS: The key workshop conclusions for adjuvant RCC therapy clinical trials were as follows. First, patients with non-clear cell RCC could be routinely included, preferably in an independent cohort. Second, patients with T3-4, N+M0, and microscopic R1 RCC tumors may gain the greatest advantages from adjuvant therapy. Third, trials of agents not excreted by the kidney should not exclude patients with severe renal insufficiency. Fourth, therapy can begin 4 to 16 weeks after the surgical procedure. Fifth, patients undergoing radical or partial nephrectomy should be equally eligible. Sixth, patients with microscopically positive soft tissue or vascular margins without gross residual or radiologic disease may be included in trials. Seventh, all suspicious regional lymph nodes should be fully resected. Eighth, computed tomography should be performed within 4 weeks before trial enrollment; for patients with renal insufficiency who cannot undergo computed tomography with contrast, noncontrast chest computed tomography and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be performed. Ninth, when feasible, biopsy should be undertaken to identify any malignant disease. Tenth, when biopsy is not feasible, a uniform approach should be used to evaluate indeterminate radiologic findings to identify what constitutes no evidence of disease at trial entry and what constitutes radiologic evidence of disease. Eleventh, a uniform approach for establishing the date of recurrence should be included in any trial design. Twelfth, patient perspectives on the use of placebo, conditions for unblinding, and research biopsies should be considered carefully during the conduct of an adjuvant trial. CONCLUSIONS AND RELEVANCE: The discussions suggested that a uniform approach to eligibility criteria and radiologic disease assessment will lead to more consistently interpretable trial results in the adjuvant RCC therapy setting.

Pragmatic randomised clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the Radiotherapy Comparative Effectiveness (RadComp) Consortium trial protocol.

INTRODUCTION: A broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer. METHODS: We are conducting a large scale, multicentre pragmatic randomised clinical trial for patients with breast cancer who will be followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life and cancer control outcomes. A total of 1278 patients with non-metastatic breast cancer will be randomly allocated to receive either photon or proton therapy. The primary outcomes are major cardiovascular events, defined as myocardial infarction, coronary revascularisation, cardiovascular death or hospitalisation for unstable angina, heart failure, valvular disease, arrhythmia or pericardial disease. Secondary endpoints are urgent or unanticipated outpatient or emergency room visits for heart failure, arrhythmia, valvular disease or pericardial disease. The Radiotherapy Comparative Effectiveness (RadComp) Clinical Events Centre will conduct centralised, blinded adjudication of primary outcome events. ETHICS AND DISSEMINATION: The RadComp trial has been approved by the institutional review boards of all participating sites. Recruitment began in February 2016. Current version of the protocol is A3, dated 08 November 2018. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets. TRIAL REGISTRATION NUMBER: NCT02603341.

Patients' early engagement in research proposal development (PEER-PD): patients guiding the proposal writing.

Patient engagement often starts after research funding is secured with little or no involvement of patients in the proposal development phase. This paper compares three levels of patient engagement and describes patients' early engagement in research proposal development process and its contemporary relevance to clinical and translational research. Authentic patient engagement is illustrated using an example of an ongoing pragmatic clinical trial. The paper also addresses key patient considerations and questions that have an impact on the proposal development. The final section presents strategies to overcome challenges to the patients' early engagement in research proposal development approach from the perspectives of both patients and researchers. Although the examples are from comparative effectiveness research, strategies discussed can be applied to all clinical and translational research.

Delivering Coordinated Cancer Care by Building Transactive Memory in a Team of Teams.

Cancer care delivery is highly complex. Treatment involves coordination within oncology health-care teams and across other teams of referring primary and specialty providers (a team of teams). Each team interfaces with patients and caregivers to offer component parts of comprehensive care. Because patients frequently obtain specialty care from divergent health-care systems resulting in cross-system health-care use, oncology teams need mechanisms to coordinate and collaborate within and across health-care systems to optimize clinical outcomes for all cancer patients. Transactive memory is one potential strategy that can help improve comprehensive patient care delivery. Transactive memory is a process by which two or more team professionals develop a shared system for encoding, storing, and retrieving information. Each professional is responsible for retaining only part of the total information. Applying this concept to a team of teams results in system benefits wherein all teams share an understanding of specialized knowledge held by each component team. The patient's role as the unifying member of the team of teams is central to successful treatment delivery. This clinical case presents a patient who is receiving oral treatment for advanced prostate cancer within two health systems. The case emphasizes the potential for error when multiple teams function without a point team (the team coordinating efforts of all other primary and specialty teams) and when the specialty knowledge of providers and patients is not well integrated into all phases of the care delivery process.

Recommended patient-reported core set of symptoms to measure in adult cancer treatment trials.

BACKGROUND: The National Cancer Institute's Symptom Management and Health-Related Quality of Life Steering Committee held a clinical trials planning meeting (September 2011) to identify a core symptom set to be assessed across oncology trials for the purposes of better understanding treatment efficacy and toxicity and to facilitate cross-study comparisons. We report the results of an evidence-synthesis and consensus-building effort that culminated in recommendations for core symptoms to be measured in adult cancer clinical trials that include a patient-reported outcome (PRO). METHODS: We used a data-driven, consensus-building process. A panel of experts, including patient representatives, conducted a systematic review of the literature (2001-2011) and analyzed six large datasets. Results were reviewed at a multistakeholder meeting, and a final set was derived emphasizing symptom prevalence across diverse cancer populations, impact on health outcomes and quality of life, and attribution to either disease or anticancer treatment. RESULTS: We recommend that a core set of 12 symptoms--specifically fatigue, insomnia, pain, anorexia (appetite loss), dyspnea, cognitive problems, anxiety (includes worry), nausea, depression (includes sadness), sensory neuropathy, constipation, and diarrhea--be considered for inclusion in clinical trials where a PRO is measured. Inclusion of symptoms and other patient-reported endpoints should be well justified, hypothesis driven, and meaningful to patients. CONCLUSIONS: This core set will promote consistent assessment of common and clinically relevant disease- and treatment-related symptoms across cancer trials. As such, it provides a foundation to support data harmonization and continued efforts to enhance measurement of patient-centered outcomes in cancer clinical trials and observational studies.

Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline.

PURPOSE: To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors. METHODS: A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life. RESULTS: A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. RECOMMENDATIONS: On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted.