Enrollment Of Patients In Clinical Trials Research Articles

A systematic review of the barriers and facilitators impacting patient enrolment in clinical trials for lung cancer

PurposeClinical research trials are needed to enhance the medical care and treatment for lung cancer, which remains the leading cause of cancer-related deaths worldwide. While clinical trials allow for the development of novel therapies to treat cancer, the recruitment of lung cancer patients to trials is low. This review aimed to identify and synthesise the available literature concerning barriers and facilitators affecting lung cancer patients’ decisions to enrol in clinical trials to guide future cancer research efforts. MethodsFour databases were systematically searched: Academic Search Complete, CINHAL, PubMed, and PsycINFO in August 2023. A supplemental grey literature search was also conducted alongside this. Articles were quality appraised using CASP and JMI checklists, and results were narratively synthesised. ResultsEighteen articles of varied design met the inclusion criteria, and results were mapped onto the Capability, Opportunity, and Motivation Behaviour (COM-B) Model to help structure and conceptualise review findings. Evidence suggests that the decision to enrol in a trial is multifaceted and informed by: when and how study information is presented, travel and trial eligibility, and altruistic hopes and fears. ConclusionsThere is need to address the many different concerns that lung cancer patients have about participating in a clinical trial through the supply of accessible and timely trial information, and via the reduction of travel, expansion of study eligibility criteria, and recognition of a person's altruistic wishes, hopes, fears, and family-oriented concerns. Future research should aim to work alongside lung cancer patients, clinicians, and other stakeholders to increase research accessibility.

How we approach early phase clinical trial and off-label therapy consults in pediatric oncology: The New Agents and Innovative Therapy (NAIT) team experience

In the context of hard-to-cure disease, pediatric oncologists may have to explore novel therapy options and explain their rationale, risks and constraints to patients and caregivers. The New Agents and Innovative Therapy (NAIT) program at Hospital for Sick Children in Toronto facilitates patient enrollment in clinical trials as well as access to innovative therapies outside of clinical trials. Here, we summarize our experience with helping patients, caregivers, and their primary oncology team navigate information and access to new therapeutic options through enrollment in clinical trials but also off-label and compassionate use. We expose our approach to exploring clinical trial and other therapy options. We share lessons learned from clinical practice regarding the specific role of NAIT consultant, as opposed to the primary oncologist or the disease expert. We expand on ways to communicate regarding the objectives of early phase clinical trials, their methods and the important commitment asked from participants. We describe our views on equipoise, uncertainty and hope in this very specific practice. We support a model of shared decision making and empowerment of patients and caregivers. We also detail the use, benefits and challenges of virtual care applied to NAIT consults. Overall, we hope to contribute and facilitate the NAIT practice not only for trained trialists but also less-specialized teams.

Abstract A063: Critical factors influencing clinical trial enrollment and autologous stem cell transplantation in African-American patients with multiple myeloma: A retrospective, interview-based analysis

Abstract Purpose: The backbone of multiple myeloma (MM) therapy include chemotherapy, targeted therapies, autologous stem cell transplantation (ASCT), amongst others. Patient enrollment in clinical trials and uptake of complex interventions such as ASCT is crucial for these advancements and to improve patient outcomes. Furthermore, MM is more than twice as common in Black/African-American (B/AA) persons, yet many B/AA people decline to enroll in clinical trials or undergo transplant. However, at the Cleveland Clinic, many B/AA patients do elect to undergo ASCT and enroll in clinical trials. We interview these patients to understand the conditions under which B/AA patients elect trial/transplant. Experimental Procedures: To study differences in access to care, which have the potential to lead to differences in survival and disease progression, we conduct semi-structured interviews with patients to better understand the breadth of their complex decision making about electing trial/transplant. We gather rich descriptive patient perceptions about their experiences on and with other novel therapies including understanding how these interventions were described by their healthcare teams and the factors that were most influential in rendering their decisions. The study includes two arms: patients who elected trial/transplant and a second cohort of B/AA patients comprised of patients matched for disease state and socioeconomic attributes who did not elect to undergo these interventions. In concert with these qualitative evaluations, we collect and analyze quantitative and categorical data regarding disease response, survival, post-protocol therapies where applicable, and patient reported outcomes including healthcare associated quality of life. We also analyze follow up surveys and a range of patient reported outcomes data collected throughout the patient’s treatment. Data Summary: We examine the impact of critical social and disease-related factors, including income, health insurance status, access to caregiving, understanding of the disease process, initial point of access to the healthcare system, health literacy, and perception of the intervention on the decision to enroll or decline enrollment in clinical trials or undergo ASCT. Conclusion: Our findings examine the mechanisms behind patient enrollment in clinical trials/transplant. B/AA patients comprise only 4% of enrollees in large MM trials worldwide. Many studies have also demonstrated that B/AA patients are less likely to undergo ASCT and are more likely to do so later in their disease course. Furthermore, a study conducted in the Veterans Affairs health system showed that with equal access to care for MM, B/AA patients actually have superior overall survival as compared to their white counterparts. We focus on patient’s complex decision making process, to provide better care and expand diverse research on MM. Study implications include improving equity in MM care for B/AA patients. Citation Format: Louis Williams, Heathe M. Hurwitz, Tiffany Onger, Diana Basali. Critical factors influencing clinical trial enrollment and autologous stem cell transplantation in African-American patients with multiple myeloma: A retrospective, interview-based analysis [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A063.

Perceptions and Practices of Clinical Trial Enrollment Among Patients with Non-Hodgkin Lymphoma, Caregivers, and Providers

BACKGROUND : Clinical trials are critical to evaluate new therapies in non-Hodgkin lymphoma (NHL) and to enhance patient outcomes; however, accrual to these studies remain low. 1 Multiple patient- and healthcare provider (HCP)-related barriers contribute to the persistently low rates of trial participation. 2 Low enrollment in cancer clinical trials result in delays in the advancement of cancer research, as well as an escalation in the cost of developing and disseminating effective treatments. 2 HCPs play a critical role in advising, motivating, and recruiting patients to clinical trials. We designed a patient-provider tethered educational initiative in collaboration with the Leukemia and Lymphoma Society and BlackDoctors.org that examined real-world experiences and perceptions of clinical trials among HCPs, patients with NHL, and their caregivers. METHODS : Two educational activities were designed: The 1-hour patient/caregiver activity was broadcasted on CancerCoachLive.com in February 2023 and featured a multidisciplinary NHL expert panel of two hematologists/oncologists and a nurse practitioner. This program addressed the value of clinical trials, diverse representation, novel therapies under investigation, and real-world experiences from a patient panel. The complementary 1-hour HCP program was hosted on OMedLive.com in March 2023 and featured the same multidisciplinary NHL expert faculty panel and included pre-recorded patient interviews and an interactive live Q&A. The online programs remain on-demand for one-year post-activity. Attitudes toward clinical trials were assessed in both activities (patient and HCP). Additionally, the HCP survey assessed barriers and challenges managing patients with NHL and intent to modify treatment plans post-program were also assessed. RESULTS : To date, 1,706 HCPs and 2,119 patients with NHL or their caregivers participated in this educational initiative. Of the HCPs, 78% were hematologists/oncologists, 15% practice at an academic medical center, 26% practice at a community hospital, and 65% manage an average of 15 patients with NHL per week. Of the patients/caregivers, 72% identified as White, 17% were Black/African American, 7% were Hispanic, 4% were Native Hawaiian/Pacific Islander, and 67% were ≥65 years old. Most of the participants (89%) in the patient/caregiver activity were ≥55 years old, 67% were >65 years. At the time of the assessment, 31% of patients were receiving watch and wait, 15% were in remission, 15% had recurrent/relapsed disease, and 12% reported having had newly diagnosed NHL. Most patients (93%) indicated that they have not participated in a clinical trial but were open to discussions with their HCPs. Patients and their caregivers expressed a high degree of interest in clinical trials. Specifically, 78% of respondents indicated that they would participate in a clinical trial if they were eligible. There were misalignments in patient-provider perceptions regarding the top patient concerns when considering participation in a clinical trial. Patients or their caregivers cited potential side effects (50%), associated costs of treatment (20%), and transportation/lack of time or resources (20%) as their top concerns related to clinical trial participation. HCPs cited fear of the unknown (34%), potential side effects (27%), and potential associated costs (15%) as their top concerns. Post-activity, 64% of patients or their caregivers indicated that they were confident in discussing clinical trials with their HCP. HCPs reported that the most common barrier to patient enrollment in clinical trials they were motivated to address at their institution post-activity were lack of clinical trials at their institution or geographic region (51%) and patient lack of interest (28%). CONCLUSIONS: These data from large groups of HCPs, patients, and caregivers provided valuable insights into patient, caregiver, and provider perceptions of clinical trials and strong willingness on the part of patients with NHL to participate in trials. Importantly, we found that targeted educational interventions can enable most patients and caregivers to feel confident in discussing clinical trials with their HCP and can motivate HCPs to increase clinical trial opportunities for diverse populations of patients with NHL. Unger JM, et al. Am Soc Clin Oncol Educ Book. 2016; 35:185-198.Ford JG et al. Cancer. 2008; 112:228-242.

Addressing barriers in care management, shared decision-making alignment, and educational needs on novel immunotherapy combinations in melanoma.

309 Background: Immunotherapy is being used increasingly to treat patients with locally-advanced unresectable or metastatic melanoma. To optimize patient care, members of the multidisciplinary healthcare team and their patients need up-to-date information about the latest therapies and the myriad factors that can influence outcomes. To assess patient-clinician alignment on perceptions of care, an educational initiative was designed for clinicians and patients/caregivers. Methods: A patient/caregiver educational activity was held in January 2023 in partnership with the Melanoma Research Foundation and remains on-demand at CancerCoachLive.com. An accredited clinician activity was held in February 2023 in collaboration with Partners for Advancing Clinical Education and remains on-demand at OMedLive.com. The Melanoma Action Coalition collaborated on both the patient and clinician activities. Behavioral assessment of preferences, attitudes, and barriers toward managing patients with melanoma were examined throughout the CME and patient/caregiver program. Data from these sessions were analyzed to determine behavioral and/or practice impact. Outcomes from the patient program were analyzed and provided as a supplemental resource for participants in the CME activity. Results: To date, 456 patients and 2,797 clinicians have participated in the educational initiative. Of the patient-reported experiences and preferences: 43% indicated they are under the care of a multidisciplinary team and only 42% were very satisfied with their current treatment regimen. The top two identified barriers in managing melanoma were anxiety about treatment efficacy (33%) and participating in normal activities (25%); these barriers were not aligned with those identified by clinicians. Upon evaluation of confidence in treatment decision-making; 70% of patients were not confident collaborating with their team while 74% of clinicians indicated low confidence in shared decision-making with their patients. At baseline, there was low awareness of safety and efficacy data regarding novel immunotherapy combinations and only 50% were likely to consider administering novel combinations to patients with unresectable locally advanced or metastatic melanoma. Clinicians additionally provided insight into barriers to patient enrollment in clinical trials with lack of trials at their institution being the greatest barrier (56%). Conclusions: Patient and clinician assessments provided an opportunity to determine misalignments in perceptions of barriers and insights into patient care experiences as well as clinician education needs. As novel immunotherapy combinations continue to become available for patients with unresectable melanoma, it is important to increase awareness of the clinical data and foster practical strategies to improve patient-centered care.

#5542 THE ITALIAN REGISTRY OF POLYCYSTIC KIDNEY DISEASE (RIRP): DESIGN, PATIENT CHARACTERISTICS AND INITIAL RESULTS

Abstract Background and Aims ADPKD is the most common form of inherited renal disease worldwide. ADPKD care has advanced over the past decade by the identification of several clinical/genetic risk factors of progression and approval of first disease-modifying drug. Further clinical outcomes research is needed to improve patient-centered clinical care; in addition new disease-modifying therapies are in pipeline, requiring a growing need for patient enrolment in clinical trials. To advance these goals, the Italian Society of Nephrology, supported by the Italian PKD Foundation (AIRP) established in 2020 the creation of a National web-based ADPKD Registry. Here we present the design of this Registry and the preliminary results. Method Adult patients with clinical or genetically confirmed diagnosis of ADPKD have been enrolled in the Registry, hosted by a secure online platform including both a clinical and genetic database. Databases have modular design collecting clinical features, including demographic data, type of diagnosis, e-GFR at onset and at time of first and last nephrological referral, age at onset of hypertension (HTN) and major urological complications (UC), Total Kidney Volume (hTKV) and Mayo Imaging Classification of ADPKD, age at ESRD, use of aspecific renal-protective and disease-modifying drugs, additional risk factors for CKD progression (smoke, diabetes, NSAID), extra-renal manifestations. Genetic data collected include type of PKD1/2 variant with ACMG classification and pathogenic prediction tools, testing method, results of segregation analysis. Statistics included estimation of eGFR slope using linear-mixed modelling. Results By January 2023, the Registry had recruited 985 ADPKD patients across 21 Italian Nephrology Unit; 513 (52,1%) were females; 967 (98,2%) Caucasians. Familiar history of ADPKD was reported in 738 patients (79%). All CKD stages were represented and 105 (14,1%) patients reached ESRD (median age 57y ± 11,5). hTKV was available for 353 (35,9%) patients, with a median value of 1100 ± 996 ml/m; a Mayo class of 1C or higher was found in 221 (70,4%). PROPKD score was evaluated in 162 patients, and in 50% of them it was associated with low risk of progression. A total of 191 (21,6%) were receiving Tolvaptan. Demographic and clinical characteristics are summarized in Table 1. Genetic testing was performed in 288 patients; 111 (38,5%) had PKD1 truncating (T) variants; 67 (23,3%) PKD1 non truncating variants; 69 (24%) PKD2 variants. In 41 patients (14,2%) no pathogenic variants were detected. In our cohort deterioration of renal function over time, estimated using eGFR slope was significantly associated with Mayo Imaging classes, high-medium PROPKD score, PKD1-T variant, HTN onset before 35 yo (Figure) and early UC (−2,3 vs. −1,9 ml/min/1.73m2/y, p = 0.014). Conclusion The Italian ADPKD National Registry is an important research tool collecting clinical and genetic information. Our preliminary data confirm that in the Italian population genotype, early onset HTN or UC, Mayo Imaging classification and PROPKD score are able to predict deterioration of GFR in ADPKD. The future empowerment of the Registry will provide a comprehensive description of clinical features and genetic variants related to ADPKD in a large cohort of Italian patients, enabling us to better understand genotype-phenotype correlation. Furthermore, the Registry could be an opportunity to identify patients suitable for future clinical trials or observational studies concerning specific aspects of the disease.

The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy: Key Points and Notes on Revisions

The Movement Disorder Society (MDS) Criteria for the Diagnosis of Multiple System Atrophy (MSA) is a new diagnostic criteria which aimed to improve the accuracy of diagnosis in the early stages of the disease, leading to improved patient enrollment in clinical trials. The criteria is characterized by four levels of diagnostic certainty: neuropathologically established MSA, clinically established MSA, clinically probable MSA, and possible prodromal MSA. This article describes the differences between the new diagnostic criteria and the second consensus statement on the diagnosis of multiple system atrophy, and also provides some points to consider when using the new criteria in daily practice.

Design and Basic Characteristics of a National Patient-Powered Registry in ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease worldwide. Over the past five years, the therapeutic pipeline for ADPKD has expanded, leading to a growing need for patient enrollment in clinical trials and improved understanding of patient-centered outcomes that can be used in trial design. To advance these goals, the Polycystic Kidney Disease Foundation (PKDF) established a national web-based ADPKD Registry. The ADPKD Registry is hosted on a secure, HIPAA-compliant, online platform (IQVIA, oc-meridian.com/pkdcure). Participants are consented through the online system and complete a series of modules. The Core Questionnaire includes patient-reported diagnosis, latest creatinine values, and comorbidities. Additional modules include surveys of family history, diet, quality of life, extrarenal manifestations, and attitudes surrounding research participation. As of October 2021, 1563 ADPKD patients across the United States have registered and completed the Core Questionnaire. Participants have a median age of 44 years and are 72% women, 93% White, with 4% self-identifying as Hispanic/Latino and 2% as Black. All CKD stages are present, including post kidney transplant. To date, seven clinical studies have used the Registry as a recruitment tool. Additionally, quality-of-life burden scores revealed a correlation with disease stage as determined by kidney function. The Registry described here is the only one of its kind and is a valuable longitudinal research tool encompassing all stages of ADPKD. The registry will allow investigators to pursue a range of research questions related to the management of ADPKD, including definition of health-related quality of life (HRQoL) outcomes and recruitment for a variety of observational and therapeutic clinical protocols.

Enhancing accrual to clinical trials of minority patients with gynecologic malignancy.

e13535 Background: Central to improving survival of patients with gynecologic malignancy is participation in therapeutic, surgical and preventative clinical trials. Minority population accrual is particularly poor representing a disparity in cancer care. We sought to evaluate enrollment of minority populations at an urban NCI-designated Comprehensive Cancer Center before and after the NCI call to action June 2020. Methods: Data on patient enrollment in gynecologic oncology clinical trials (14 therapeutic and 4 non-therapeutic) was obtained from Perlmutter NCI-designated Comprehensive Cancer Center. Primary outcomes were the proportion of newly accrued patients by race participating in trials between January 2019 to September 2021. Results: Over the entire study period 154 total patients were enrolled in therapeutic and non-therapeutic clinical trials. Enrollment by cancer type included 100 (71.4%) ovarian, 16 (7.1%) uterine, 12 (7.9%) cervical and 26 (13.5%) solid tumor trials. White patients comprised 69% (69 of 100) of patients on ovarian cancer trials. Uterine cancer trials by race consisted of 50 % White, 37.5% Black, 6.2% Asian and 6.2% Other race patients. Eighty-eight patients were enrolled into clinical trial prior to the NCI alert. By race these patients were: White, 65.9% (58 of 88); Black, 3.4% (3 of 88); Asian, 11.4% (10 of 88) and Other race, 19.3% (17 of 88). Hispanic patients comprised 13.6% (12 of 88) of the population. Following the call to action an additional 66 patients were enrolled in clinical trial. This included 42 (63.6%) White, 14 (21.2%) Black, 5 (7.57%) Asian, 5 (7.6%) Other race and 8 (12.12%) Hispanic patients. The percentage of Black patients enrolled in clinical trial increased four -fold over the time period (3.4% vs 21.2%, p < 0.05). Conclusions: Overall during this time period we found an increase in number of Black patients accrued to clinical trial. This indicates disparities in clinical trial enrollment can be modified by institutional awareness. The role of patient education, financial and logistical barriers and language discordance to minority participation in clinical trials should be studied further.

Evaluation of tumor gene expression profile (GEP) in minority patients with stage IV non-small cell lung cancer (NSCLC).

e21043 Background: Differences in tumor gene expression profile (GEP) may contribute to disparities in lung cancer incidence and survival between racial and ethnic groups. For patients with stage IV NSCLC, tumor biomarker analysis is important for identification of potentially effective targeted therapies. However, despite advancements in biomarker testing and targeted therapy, minority patient enrollment in clinical trials remains low and it has been shown that minority patients are less likely to undergo next-generation sequencing (NGS) compared to Non-Hispanic Whites (NHW). As such, frequencies of tumor biomarkers in minority populations in the United States are not well-defined. This study aimed to determine the extent of tumor GEP diversity in minority patients vs NHW. Methods: This retrospective study included 196 adult patients with stage IV NSCLC that had a baseline NGS of tumor tissue or blood (liquid biopsy) performed between July 1, 2015 and June 30, 2021. Minority populations included Hispanic, African American, and Asian patients. Data collected utilizing the electronic medical record included patient demographics, detection of tumor biomarkers and treatment initiated. Descriptive statistics were calculated for all demographic and clinical variables. Comparisons of actionable epidermal growth factor receptor (EGFR) mutation frequency between NHW and minority patients were done using Chi-squared and Fisher’s exact tests. Results: Of the 196 patients evaluated, baseline characteristics included 46% male, 67% former smokers, 54% NHW, 31% Hispanic, 9% African American, 5% Asian, and 1% other. The median age at diagnosis was 66 ± 12 years. Actionable mutations (EGFR, KRAS, BRAF, ROS-1, ALK, MET, NTRK 1-3) were found in 50% of patients (see Table). The frequency of actionable EGFR mutations was higher in minority patients overall compared to NHW (39.3% vs 21.5%; p < 0.01). The frequency of actionable EGFR mutations was similar between NHW and Hispanic patients (21.5% vs 27.9%; p = 0.35), however differences were observed comparing NHW to African American (21.5% vs 50%; p = 0.02) and Asian (21.5% vs 90%; p < 0.01) patients, respectively. Conclusions: Among patients with stage IV NSCLC, the GEP of minority patients varied from that of NHW. Asian patients had the highest frequency of EGFR mutations, followed by African American and Hispanic patients, respectively. Larger studies are needed to validate these findings.[Table: see text]

Opportunities for Participation in Randomized Controlled Trials for Patients with Multiple Myeloma: Trial Access Depends on Restrictive Eligibility Criteria and Patient Expectations.

Simple SummaryOver the past decade, randomized controlled trials as an established instrument of evidence-based medicine have contributed fundamentally to the development and approval of new substances. However, it has been frequently shown that less than 5% of adult cancer patients enroll in clinical trials. Barriers to trial participation have been extensively studied, but the rate of trial participation has not changed substantially. In this retrospective analysis, we found that 53% of newly diagnosed multiple myeloma patients met the eligibility criteria, while only 38% of relapsed refractory patients were eligible. Moreover, our data show for the first time that eligible patients tend to become more reluctant to participate over the course of the disease, with 42% of newly diagnosed patients consenting, and only 7% of relapsed/refractory patients consenting. Thus, our results may assist with trial design improvements and address patient expectations and priorities in order to increase enrollment.Randomized controlled trials (RCT) are the driver of therapeutic innovations. However, it has been frequently shown that less than 5% of adult cancer patients enroll in clinical trials, although 70% of patients are considered as being willing to participate. Barriers to trial participation have been extensively studied. Although there is evidence that trial participation correlates with improved survival and reduced mortality, the rate of participation has not changed substantially. We provide retrospective data from a single-center analysis of 411 patients with multiple myeloma (MM) who were treated at the University Hospital Duesseldorf in Germany between January 2014 and December 2016. Each patient was analyzed for the real-world possibility of participating in a clinical study, based on the inclusion and exclusion (I/E) criteria and the recruiting period of open studies. The overall rate of study participation was 19%. A total of 53% of NDMM patients were eligible for first-line studies (GMMG-HD6, LenaMain). Of these, 80% consented to enrolment (42% of all). In contrast, only 38% of the RRMM population was eligible (GMMG-Relapse, Castor, Tourmaline, Admyre). Of these, only 22% (7% of all) consented. This was confirmed by virtual analysis, showing that only 29% of all RRMM patients would have been eligible for six internationally recruiting trials leading to later drug approval. The majority of cases were rendered ineligible by only one I/E criterion. The most common criteria were study-specific (prior therapies or refractory disease to a specific drug), kidney disease, and previous malignancy, followed by internal, neurologic, and infectious disease. In summary, this single-center analysis showed that I/E criteria permit study participation for most NNDM patients, with a dramatic decrease in the RRMM population. This is aggravated by the fact that the willingness for study participation also significantly declines in RRMM. Thus, addressing patient expectations and priorities seems to be the most promising approach to increasing patient enrollment in clinical trials.

Toward Bridging Unmet Medical Need in Early Alzheimer's Disease: An Evaluation of Beta-Amyloid (Aβ) Plaque Burden as a Potential Drug Development Tool.

Toward Bridging Unmet Medical Need in Early Alzheimer's Disease: An Evaluation of Beta-Amyloid (Aβ) Plaque Burden as a Potential Drug Development Tool.

POS-359 Developing targeted therapies for kidney disease in public private partnerships

Integrating public and private research efforts is key to expediting precision medicine for glomerular diseases. The Nephrotic Syndrome Study Network (NEPTUNE) has developed an innovative research and business model: “MATCH”, to enable targeted patient enrollment in clinical trials via the NEPTUNE public private partnership (NP5). The NEPTUNE community knowledge base is leveraged to identify a molecular signal matching therapeutic targets under development by NP5 industry partners. The three steps of MATCH are: (1) predictive biomarker development; (2)patient communication about precision medicine; and (3) return of results from NP5 partner clinical trials for evaluation of patient stratification effects on trial outcomes. MATCH begins with NEPTUNE patient education on risks and benefits of the study. Once enrolled in MATCH, a patient’s biosamples undergo biomarker profiling. MATCH provides individual pathway activation information to patients for consideration in their independent decision to enroll in a trial that may be more tailored to their specific disease and stage. Finally, clinical trial outcomes will be reported by NP5 partners to NEPTUNE to evaluate the MATCH impact on treatment responses. MATCH aims to assess the ability to communicate molecular information to patients, and to test precision medicine across multiple trials and partners to move science closer to the overall goal: reaching the right patient with the right medicine at the right time. MATCH is an open framework available to additional partners interested in joining NP5.

Impact of the First Wave of the COVID-19 Pandemic on the Lyon University Hospital Cancer Institute (IC-HCL)

Simple SummaryThis article presents the protective measures put in place at the “Institut de Cancérologie des Hospices de Lyon” (IC-HCL) during the first wave of the COVID-19 pandemic in France (spring 2020) and how they impacted IC-HCL clinical activity. Spring 2020 activities were compared to winter 2019–2020. This article presents the protective measures put in place at the “Institut de Cancérologie des Hospices de Lyon” (IC-HCL) during the first wave of the COVID-19 pandemic in France (spring 2020) and how they impacted IC-HCL clinical activity. Spring 2020 activities were compared to winter 2019–2020. Results showed a decrease of activity of 9% for treatment dispensations, 17% for multidisciplinary team meetings, 20% for head and neck and thoracic surgeries, and 58% for new patient enrolment in clinical trials. Characteristics of patients treated for solid cancer and hospitalized for COVID-19 during spring 2020 were collected in a retrospective study. Mortality was attributed to COVID-19 for half of the cases, 82% being patients above 70 and 73% being stage IV. This is in concordance with current findings concluding that the risk of developing severe or critical symptoms of COVID-19 is correlated with factors co-occurring in cancer patients and not to the cancer condition per se. While a number of routines and treatment regimens were changed, there was no major decline in numbers of treatments conducted at the IC-HCL during the first wave of the COVID-19 pandemic that hit France between March and May 2020, except for clinical trials and some surgery activities.

Accelerating cancer clinical trial recruitment through a financial reimbursement program integrated with patient navigation: an interrupted time series analysis

BackgroundCancer treatment clinical trials face major challenges with patient recruitment. Strategies to address patient indirect costs associated with clinical trial participation may accelerate accrual overall. The current study examined the effect of the IMproving Patient Access to Clinical Trials (IMPACT) intervention on patient accrual to cancer treatment clinical trials at an academic medical center. The IMPACT intervention was an onsite patient navigator combined with a financial reimbursement program to address patient out of pocket costs and began on September 2018. MethodsThis analysis measured frequency of patient enrollment in cancer treatment clinical trials and available cancer treatment clinical trials per month between January 1, 2016 and March 31, 2020. An interrupted time-series analysis (ITSA) was conducted to estimate changes in patient enrollment attributable to the IMPACT intervention. ResultsDuring the study period, a mean of 69 patients enrolled in clinical trials per month (standard deviation (SD = 13), with 27 (SD = 7) in early phase vs 41 (SD = 12) in late phase clinical trials. The number of available clinical trials per month was 51 (SD = 2) overall, with 23 (SD = 1) in early phase vs 28 (SD = 1) in late phase context. A total of 3470 patients were enrolled in cancer treatment clinical trials during the evaluated time period, the majority of whom were men (1895, 55 %) and racially white (2267, 65 %). A statistically significant increase in the number of patients accrued as compared to the pre-intervention trend was observed; with approximately 1 additional patient accrued per month, with a larger effect on increase patient accrual for late phase clinical trials. DiscussionThis study observed that the IMPACT intervention accelerated clinical trial recruitment, especially among late phase clinical trials. Future research will examine strategies to leverage this infrastructure to optimize recruitment among underrepresented patients. Policy summaryTo improve clinical trial recruitment and ensure that trial results are representative of a diverse population it is critical for health policies consider patient out-of-pocket costs and potential reimbursement to alleviate financial burden associated with clinical trial participation. Furthermore, policies for facilitating clinical trial recruitment and participant retention should budget for and incorporate a navigation component to assist patients who may not be familiar with the healthcare system and available financial assistance.

Impact of COVID-19 on Hepatocellular Carcinoma Management: A Multicountry and Region Study.

PurposeThe COVID-19 pandemic has altered healthcare priorities which may adversely impact cancer management. We aimed to evaluate the impact of the pandemic on the diagnosis, treatment, and consultation methods for patients with hepatocellular carcinoma (HCC).Patients and MethodsWe conducted a survey among 27 hospitals from 14 Asia-Pacific countries, collecting hospital-level information on the number of newly diagnosed HCC cases during a pre-pandemic period (February to May 2019) and for the same period during the pandemic (February to May 2020). Information was also collected on delays in diagnosis and treatment, changes in treatment modalities and complication rates, changes in patient enrollment in clinical trials, and modes of patient consultation. The information was stratified by the Barcelona Clinic Liver Cancer (BCLC) stage.ResultsThe survey included cohorts of 2789 and 2045 patients newly diagnosed with HCC during the pre- and pandemic period, respectively. A decline of 26.7% in new HCC cases was reported during the pandemic compared to the pre-pandemic. A sizable proportion of institutions reported delays in diagnosis (48.2% in BCLC 0/A/B and 51.9% in BCLC C), delays in treatment (66.7% in BCLC 0/A/B and 63.0% in BCLC C), changes in treatment modality (33.3% in BCLC 0/A/B and 18.5% in BCLC C), an increase in treatment complications (about 15% across all BCLC stages), and no growth in clinical trial enrollments during the pandemic. Furthermore, there was a decline of 27.3% in face-to-face patient consultations and an increase of 18.3% in video/telephonic consultations during the pandemic. A considerable variation in changes in HCC management was observed among countries.ConclusionThe COVID-19 pandemic has significantly impacted the management of HCC among Asia-Pacific countries. The impact varies according to the disease stage and country. Well thought-through long-term strategies are required to ameliorate the negative impact of the pandemic on HCC patients.

Echocardiographic Longitudinal Strain Analysis in Heart Failure: Real Usefulness for Clinical Management Beyond Diagnostic Value and Prognostic Correlations? A Comprehensive Review.

Heart failure (HF) is a highly prevalent clinical syndrome characterized by considerable phenotypic heterogeneity. The traditional classification based on left ventricular ejection fraction (LVEF) is widely accepted by the guidelines and represents the grounds for patient enrollment in clinical trials, even though it shows several limitations. Ejection fraction (EF) is affected by preload, afterload, and contractility, it being problematic to express LV function in several conditions, such as HF with preserved EF (HFpEF), valvular heart disease, and subclinical HF, and in athletes. Over the last two decades, developments in diagnostic techniques have provided useful tools to overcome EF limitations. Strain imaging analysis (particularly global longitudinal strain (GLS)) has emerged as a useful echocardiographic technique in patients with HF, as it is able to simultaneously supply information on both systolic and diastolic functions, depending on cardiac anatomy and physiology/pathophysiology. The use of GLS has proved helpful in terms of diagnostic performance and prognostic value in several HF studies. Universally accepted cutoff values and variability across vendors remain an area to be fully explored, hence limiting routine application of this technique in clinical practice. In the present review, the current role of GLS in the diagnosis and management of patients with HF will be discussed. We describe, by critical analysis of the pros and cons, various clinical settings in HF, and how the appropriate use and interpretation of GLS can provide important clues.

Phenotyping Cardiogenic Shock.

BackgroundCardiogenic shock (CS) is a heterogeneous syndrome with varied presentations and outcomes. We used a machine learning approach to test the hypothesis that patients with CS have distinct phenotypes at presentation, which are associated with unique clinical profiles and in‐hospital mortality.Methods and ResultsWe analyzed data from 1959 patients with CS from 2 international cohorts: CSWG (Cardiogenic Shock Working Group Registry) (myocardial infarction [CSWG‐MI; n=410] and acute‐on‐chronic heart failure [CSWG‐HF; n=480]) and the DRR (Danish Retroshock MI Registry) (n=1069). Clusters of patients with CS were identified in CSWG‐MI using the consensus k means algorithm and subsequently validated in CSWG‐HF and DRR. Patients in each phenotype were further categorized by their Society of Cardiovascular Angiography and Interventions staging. The machine learning algorithms revealed 3 distinct clusters in CS: "non‐congested (I)", "cardiorenal (II)," and "cardiometabolic (III)" shock. Among the 3 cohorts (CSWG‐MI versus DDR versus CSWG‐HF), in‐hospital mortality was 21% versus 28% versus 10%, 45% versus 40% versus 32%, and 55% versus 56% versus 52% for clusters I, II, and III, respectively. The "cardiometabolic shock" cluster had the highest risk of developing stage D or E shock as well as in‐hospital mortality among the phenotypes, regardless of cause. Despite baseline differences, each cluster showed reproducible demographic, metabolic, and hemodynamic profiles across the 3 cohorts.ConclusionsUsing machine learning, we identified and validated 3 distinct CS phenotypes, with specific and reproducible associations with mortality. These phenotypes may allow for targeted patient enrollment in clinical trials and foster development of tailored treatment strategies in subsets of patients with CS.

How the COVID-19 Pandemic Impacted on Integrated Care Pathways for Lung Cancer: The Parallel Experience of a COVID-Spared and a COVID-Dedicated Center.

IntroductionThe COVID-19 pandemic has proved to be a historic challenge for healthcare systems, particularly with regard to cancer patients. So far, very limited data have been presented on the impact on integrated care pathways (ICPs).MethodsWe reviewed the ICPs of lung cancer patients who accessed the Veneto Institute of Oncology (IOV)/University Hospital of Padua (Center 1) and the University Hospital of Verona (Center 2) before and after the COVID-19 pandemic, through sixteen indicators chosen by the members of a multidisciplinary team (MDT).ResultsTwo window periods (March and April 2019 and 2020) were chosen for comparison. Endoscopic diagnostic procedures and major resections for early stage NSCLC patients increased at Center 1, where a priority pathway with dedicated personnel was established for cancer patients. A slight decrease was observed at Center 2 which became part of the COVID unit. Personnel shortage and different processing methods of tumor samples determined a slightly longer time for diagnostic pathway completion at both Centers. Personnel protection strategies led to a MDT reshape on a web basis and to a significant selection of cases to be discussed in both Centers. The optimization of patient access to healthcare units reduced first outpatient oncological visits, patient enrollment in clinical trials, and end-of-life cancer systemic treatments; finally, a higher proportion of hypofractionation was delivered as a radiotherapy approach for early stage and locally advanced NSCLC.ConclusionsBased on the experience of the two Centers, we identified the key steps in ICP that were impacted by the COVID-19 pandemic so as to proactively put in place a robust service provision of thoracic oncology.

Using real-word data to evaluate the effects of broadening eligibility criteria in oncology trials.

Eligibility criteria restrict patient enrollment in clinical trials. A Nature paper applied a machine-learning algorithm in a real-world database to show that relaxing some criteria may not jeopardize efficacy and safety. This may enable more patients to have earlier access to new therapies and make results more generalizable to clinical practice.