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Barriers to publishing early phase clinical trials: the oncologists’ perspective
Get PDFEthics; Medical oncology; PublicationÈtica; Oncologia mèdica; PublicacióÉtica; Oncología médica; PublicaciónIntroduction
Findings from early phase studies are not always placed in the public domain. This study aims to explore why many early phase clinical oncology studies are not published, as well as identify the potential barriers investigators encountered in the publication process.
Methods
Semi-structured interviews were conducted among investigators with experience in early phase clinical oncology studies. Interviews were analyzed using reflexive thematic analysis.
Results
Twenty-one investigators were interviewed. The majority worked in Europe (n = 13), while other investigators were based in North America (n = 4), Asia (n = 2) or Oceania (n = 2). We identified three reasons why investigators believed publishing early phase clinical trial results was important: (1) there is an ethical and moral responsibility; (2) there should be no loss of knowledge to society; and (3) there should be no waste of resources. Four main barriers in the publication process of early phase clinical trials were identified: (1) practical barriers (eg, an increased complexity of number of trials/trial sites), (2) insufficient resources (eg, money, time and human), (3) limited motivation (eg, limited intrinsic motivation of the investigator or limited prospect of return for the sponsor), and (4) inadequate collaboration (eg, different interests between industry partners and investigators). Finally, five major stakeholders were identified that can potentially contribute to improving the publication process: (1) journal editors, (2) sponsors, (3) investigators, (4) regulatory bodies, and (5) society. Investigator suggestions for improving this process, for each stakeholder, are presented.
Conclusions
This study highlights the barriers experienced in publishing early phase clinical trials. Recognizing and acknowledging these barriers is crucial to devise effective strategies to improve the publishing and public sharing of early phase clinical trials
Phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination–proficient ovarian cancer
Get PDFDNA repair; Molecular diagnosis; OncologyReparació d'ADN; Diagnòstic molecular; OncologiaReparación del ADN; Diagnóstico molecular; OncologíaBACKGROUND. Treatment of tubo-ovarian high-grade serous carcinoma (HGSC) includes cytoreductive surgery, platinum-based chemotherapy, and often poly(ADP-ribose) polymerase (PARP) inhibitors. While homologous recombination (HR) deficiency is a well-established predictor of therapy sensitivity, over 50% of HR-proficient HGSCs also exhibit sensitivity. Currently, there are no biomarkers to identify which HR-proficient HGSCs will be sensitive to standard-of-care therapy. Replication stress may serve as a key determinant of response.
METHODS. We evaluated phospho–RPA2-T21 (p-RPA2) foci via immunofluorescence as a biomarker of replication stress in formalin-fixed, paraffin-embedded HGSC samples collected at diagnosis from patients treated with platinum chemotherapy (discovery cohort, n = 31; validation cohort, n = 244) or PARP inhibitors (n = 63). Recurrent HGSCs (n = 38) were also analyzed. p-RPA2 score was calculated using automated imaging analysis.
RESULTS. Samples were defined as p-RPA2-high if more than 16% of cells had ≥2 p-RPA2 foci on automated analysis. In the discovery cohort, HR-proficient, p-RPA2-high HGSCs demonstrated significantly higher rates of a chemotherapy response score of 3 to platinum chemotherapy than HR-proficient, p-RPA2-low HGSCs. In the validation cohort, patients with HR-proficient, p-RPA2-high HGSCs had significantly longer survival after platinum treatment than those with HR-proficient, p-RPA2-low HGSCs. Additionally, the p-RPA2 assay effectively predicted survival outcomes in patients treated with PARP inhibitors and in recurrent HGSC samples.
CONCLUSION. Our study underscores the importance of considering replication stress markers, such as p-RPA2, alongside HR status in therapeutic planning. This approach has the potential to increase the number of patients receiving effective therapy while reducing unnecessary toxicity.The Reproductive Scientist Development Program, GOG Foundation, Pilot Translational and Clinical Studies function of the Washington University Institute of Clinical and Translational Sciences, the Foundation for Barnes-Jewish Hospital, Washington University School of Medicine Dean’s Scholar Program, The Cancer Biology Pathway Training Grant (5T32CA113275-17), The Lucy, Anarcha, and Betsey (L.A.B.) Award from the Department of Obstetrics and Gynecology at Washington University School of Medicine, and Veterans Affairs Office of Research and Development (I01BX006020)
Expert Clinical Management of Inflammatory Immune-Related Arthritis in Patients with Cancer Receiving Immune Checkpoint Inhibitors
Get PDFImmune checkpoint inhibitor therapy; Inflammatory arthritis; SurveyTeràpia amb inhibidors del punt de control immunitari; Artritis inflamatòria; EnquestaTerapia con inhibidores del punto de control inmunitario; Artritis inflamatoria; EncuestaIntroduction
Treatment guidelines for immune-related inflammatory arthritis (irAE-IA) in patients with cancer receiving immune checkpoint inhibitors (ICIs) are vague with respect to the use of specific agents. Patients are usually referred to rheumatologists for treatment. We conducted a survey of expert rheumatologists to determine current practices. We also assessed experts’ views on the potential deleterious effects of various agents on tumor progression.
Methods
We conducted a survey of international experts in the treatment of irAE-IA, identified as members of collaborative scientific workgroups in this area. Experts were presented with a case of a patient with moderate irAE-IA and were asked about their preferred management including glucocorticoids, timing and initial choice of disease-modifying antirheumatic drugs (DMARDs), and perception of the deleterious effects of different agents on tumor progression.
Results
We approached 25 experts, of whom 19 (76%) responded. Most experts (63%) agreed on 20 mg or less of prednisone as initial dose. Experts selected methotrexate (41%) or tumor necrosis factor inhibitor (TNFi) (23%) as the initial DMARD if there was no improvement with corticosteroids; most experts (42%) would initiate DMARDs after 4 weeks. For patients whose initial DMARD therapy failed, the second choice was either a tumor necrosis factor inhibitor (TNFi) (38%) or interleukin-6 receptor antagonist (IL6ri) (33%). Experts were most concerned about the potential deleterious effects on tumor progression of abatacept and prednisone at doses of 20 mg or higher.
Conclusion
There was substantial heterogeneity in the initial management of irAE-IA. Further understanding of the pathophysiology of this immunotoxicity can assist in the classification of different presentations, selection of relevant outcomes, and planning of clinical trials to establish optimal therapeutic efficacy while minimizing potential deleterious effects of treatment on immune tumor responses
A Systematic Literature Review on the Burden of Disease for Patients With Moderate to Severe Acute Ischemic Stroke
Get PDFBurden disease; Acute ischemic strokeCàrrega de la malaltia; Ictus isquèmic agutCarga de la enfermedad; Ictus isquémico agudoBackground:
A vast amount of literature is available on the burden of acute ischemic stroke (AIS). Yet, most information on AIS burden does not stratify by stroke severity, and the inclusion of mild strokes (National Institute of Health Stroke Scale < 5) might obscure the true impact of moderate-to-severe AIS. Therefore, it is important to understand the literature as it pertains to the epidemiological, clinical, humanistic, and economic burden of moderate-to-severe AIS from a global perspective.
Methods:
A systematic literature review (SLR) was conducted, including articles published between January 2015 and June 2023. The clinical burden search focused on patients with moderate or severe AIS. Due to the paucity of evidence, the humanistic and economic burdens were evaluated based on overall AIS studies. Abstract and full-text screening were conducted by 2 reviewers, with data extraction completed by 1 reviewer. In all, 136 studies were included in the SLR.
Results:
AIS caused a substantial burden for patients and the healthcare system. The clinical burden of AIS (specifically severe AIS) resulted in high mortality and worse functional outcomes across multiple demographics (female sex, older age, and patients with comorbidities). The economic burden of overall AIS was substantial, with inpatient costs as the primary driver (a mean or median stay of 7 days). The highest inpatient costs were reported in South Korea (38,470).
Conclusions:
The review highlighted the huge burden of moderate-to-severe AIS, with patients experiencing worse outcomes with increased stroke severity. Further focus is needed on outcomes relating to moderate-to-severe AIS to fully understand the burden of stroke in this patient population
Diagnóstico y tratamiento de los trastornos de la presión intracraneal: documento de consenso del Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología
No full textHipertensión intracraneal idiopática; Hipotensión intracraneal espontánea; Líquido cefalorraquídeoIdiopathic intracranial hypertension; Spontaneous intracranial hypotension; Cerebrospinal fluidHipertensió intracranial idiopàtica; Hipotensió intracranial espontània; Líquid cefaloraquidiPrimary intracranial pressure disorders include idiopathic intracranial hypertension and spontaneous intracranial hypotension. Remarkable advances have been made in the diagnosis and treatment of these 2entities in recent years. Therefore, the Spanish Society of Neurology's Headache Study Group (GECSEN) deemed it necessary to prepare this consensus statement, including diagnostic and therapeutic algorithms to facilitate and improve the management of these disorders in clinical practice.
This document was created by a committee of experts belonging to GECSEN, and is based on a systematic review of the literature, incorporating the experience of the participants, and establishes practical recommendations with levels of evidence and grades of recommendation.Los trastornos primarios de la presión intracraneal incluyen la hipertensión intracraneal idiopática y la hipotensión intracraneal espontánea. El diagnóstico y tratamiento de ambas entidades ha presentado un avance destacable en los últimos años; por lo que desde el Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología (GECSEN) consideramos necesaria la elaboración de este documento de consenso con la inclusión de algoritmos diagnósticos y terapéuticos para mejorar su manejo en la práctica diaria.
Este documento ha sido redactado por un comité de expertos del GECSEN tras realizar una revisión sistemática de la bibliografía, incorporando la experiencia de los participantes y estableciendo unas recomendaciones prácticas con niveles de evidencia y grados de recomendación
Avaluació dels empelts cutanis en segell en pacients amb ferides de difícil cicatrització
Get PDFEmpelts de pell autòlegs; Cicatrització de feridesInjertos de piel autólogos; Cicatrización de heridasAutologous skin grafts; Wound healingSíntesi dels principals resultats de l'informe elaborat per avaluar l’evidència disponible sobre la seguretat clínica, així com l’eficàcia i l’efectivitat comparativa dels empelts cutanis autòlegs tipus empelt en segell en pacients adults amb ferides de difícil cicatrització.Síntesis de los principales resultados del informe elaborado para evaluar la evidencia disponible sobre la seguridad clínica, así como la eficacia y la efectividad comparativa de los injertos cutáneos autólogos tipo injerto en sello en pacientes adultos con heridas de difícil cicatrización.Summary of the main results of the report prepared to evaluate the available evidence on the clinical safety, as well as the efficacy and comparative effectiveness, of autologous skin grafts of the stamp graft type in adult patients with hard-to-heal wounds
Avaluació d’una formació interactiva en avaluació de tecnologies sanitàries: resultats de la prova pilot amb pacients, cuidadors i ciutadania
Get PDFAvaluació; Tecnologies sanitàriesEvaluación; Tecnologías sanitariasEvaluation; Health technologiesAquest article presenta l’experiència d’una formació virtual
dissenyada per a capacitar pacients, familiars i usuaris
del sistema de salut en l’avaluació de tecnologies sanitàries.
Es va avaluar la proposta formativa mitjançant 10 respostes
a una enquesta. Els resultats han mostrat una elevada
satisfacció amb el contingut, el disseny i la metodologia
de la formació virtual. S’han identifcat àrees de millora
com l’accessibilitat, la tutoria i l’enriquiment dels materials
proporcionats.Este artículo presenta la experiencia de una formación virtual diseñada para capacitar a pacientes, familiares y usuarios del sistema de salud en la evaluación de tecnologías sanitarias. La propuesta formativa fue evaluada mediante 10 respuestas a una encuesta.
Los resultados mostraron una alta satisfacción con el contenido, el diseño y la metodología de la formación virtual. Se identificaron áreas de mejora como la accesibilidad, la tutoría y el enriquecimiento de los materiales proporcionados.This article presents the experience of a virtual training program designed to empower patients, relatives, and users of the healthcare system in the evaluation of health technologies.
The training program was assessed through 10 survey responses.
The results showed a high level of satisfaction with the content, design, and methodology of the virtual training.
Areas for improvement were identified, such as accessibility, tutoring, and the enhancement of the provided materials
Protocol for the enhanced management of multimorbid patients with COPD and severe asthma: role of indoor air quality
Get PDFAsthma; Patient Outcome Assessment; Pulmonary Disease, Chronic Obstructive; Respiratory Function Test; Surveys and Questionnaires; TelemedicineAsma greu; MPOC (Malaltia Pulmonar Obstructiva Crònica); Qualitat de l’aire interior; Monitoratge digitalAsma grave; EPOC (Enfermedad Pulmonar Obstructiva Crónica); Calidad del aire interior; Monitorización digitalReducing unplanned hospital admissions in chronic patients at risk is a key area for action due to the high healthcare and societal burden of the phenomenon. The inconclusive results of preventive strategies in patients with chronic obstructive respiratory disorders and comorbidities are explainable by multifactorial but actionable factors.The current protocol (January 2024-December 2025) relies on the hypothesis that intertwined actions in four dimensions: (1) management change, (2) personalisation of the interventions based on early detection/treatment of acute episodes and enhanced management of comorbidities, (3) mature digital support and (4) comprehensive assessment, can effectively overcome most of the limitations shown by previous preventive strategies. Accordingly, the main objective is to implement a novel integrated care preventive service for enhanced management of these patients, as well as to evaluate its potential for value generation.
At the end of 2024, the specifics of the novel service will be defined through the articulation of its four main components: (1) enhanced lung function testing through oscillometry, (2) continuous monitoring of indoor air quality as a potential triggering factor, (3) digital support with an adaptive case management (ACM) approach and (4) predictive modelling for early identification and management of exacerbations. During 2025, the novel service will be assessed using a Quintuple Aim approach. Moreover, the Consolidated Framework for Implementation Research will be applied to assess the implementation. The service components will be articulated through four sequential 6-month plan-do-study-act cycles. Each cycle involves a targeted cocreation process following a mixed-methods approach with the active participation of patients, health professionals, managers and digital experts.
The Ethics Committee for Human Research at Hospital Clinic de Barcelona approved the protocol on 29 June 2023 (HCB/2023/0126). Before any procedure, all patients in the study must sign an informed consent form.
NCT06421402.The K-HEALTHinAIR project funded this study, Grant Agreement nº 101057693, under a European Union’s Call on Environment and Health (HORIZONHLTH-2021-ENVHLTH-02)
Clinical Outcomes of Patients Undergoing Isolated and Combined Subscapularis Repair
Get PDFArthroscopic repair; Rotator cuff tear; Subscapularis tearReparació artroscòpica; Ruptura del manegot rotador; Ruptura del subescapularReparación artroscópica; Rotura del manguito rotador; Rotura del subescapularBackground: Subscapularis (SSC) tears can present as isolated or combined with additional rotator cuff tendon tears. The repair of SSC tear improves postoperative outcomes. However, the effect that SSC repair and healing have on functional outcomes after arthroscopic repair of isolated or combined SSC tears requires further investigation.
Purpose: To (1) compare the clinical outcomes of arthroscopic rotator cuff repair (ARCR) of isolated SSC tears with those having SSC tears combined with supraspinatus and/or infraspinatus tears and (2) evaluate the effect of SSC healing on postoperative clinical outcomes.
Study design: Cohort study; Level of evidence 3.
Methods: A retrospective study was carried out in patients who underwent ARCR of isolated or combined SSC tears with a minimum 2-year follow-up. Three groups were compared: isolated SSC tear, anterosuperior rotator cuff tear with SSC tear (AS-RCT) and posterosuperior rotator cuff tear with SSC tear (PS-RCT). Patient-reported outcomes (PROs) and range of motion (ROM) were assessed pre- and postoperatively. SSC healing was evaluated via ultrasound at the final follow-up in a subset of patients.
Results: The study included 588 patients with a minimum 2-year follow-up, of whom 279 underwent ultrasound assessments. PROs and ROM improved after ARCR in all groups (P .05), or between isolated SSC and PS-RCT groups (P > .05). There was no statistically significant difference when comparing the pre- to postoperative change in ROM between the groups (P > .05). The SSC healing rates for isolated SSC, AS-RCT, and PS-RCT groups were 88.1%, 91.6%, and 84.3%, respectively, (P >.24). There was no significant difference in ASES score or Subjective Shoulder Value (SSV) improvement between healed and unhealed groups in patients with isolated SSC tears (P > .05). ASES and SSV were significantly lower in unhealed SSC patients compared with those having a healed SSC in patients with AS-RCTs (ASES, P .01; SSV, P < .01).
Conclusion: Both isolated and combined SSC repairs showed improvement in PROs and ROM. SSC healing rates did not differ between isolated and combined SSC tears. While failure to heal did not affect the clinical outcome of isolated SSC tears, an unhealed SSC was associated with lower functional scores in combined tears. Regardless of tear type, a healed SSC was associated with increased shoulder strength
Café-Au-Lait Macules in Neurofibromatosis Type 1: Birthmark or Biomarker?
Get PDFCafé-au-lait macules; Early diagnosis; NeurofibromatosisMáculas café con leche; Diagnóstico precoz; NeurofibromatosisMàcules cafè amb llet; Diagnòstic precoç; NeurofibromatosiBackground: Neurofibromatosis type 1 (NF1) is a rare multisystem disorder characterized by variable expressivity and increased tumor risk. Café-au-lait macules (CALMs) are a hallmark of the disease, often representing one of the earliest clinical manifestations and allowing a clinical NF1 diagnosis if six or more are present. In this study, we aimed to investigate the prognostic value of CALMs at birth in NF1 patients. Methods: We conducted a retrospective study in patients aged ≥ 4 years presenting with CALMs at our Institution between 2020 and 2021, with a minimum follow-up of four years. We retrospectively collected data on CALMs at birth and other clinical manifestations associated with NF1. Results: Among 208 patients evaluated, including 147 with a confirmed diagnosis of NF1, 110 did not show CALMs at birth, and 98 had at least one. The absence of CALMs at birth did not correlate with a lower likelihood of NF1. In contrast, the CALM number at birth directly correlated with the likelihood of NF1, up to 95% in patients with ≥5 macules. Additionally, a higher number of CALMs correlated with a greater prevalence of plexiform neurofibromas (p < 0.001). Conclusions: Our findings suggest that a higher number of CALMs may indicate a more severe form of NF1, with an increased risk of plexiform neurofibromas. These results emphasize the importance of a comprehensive evaluation of patients with CALMs, especially in case of multiple lesions, aiming at implementing early NF1 diagnosis, follow-up strategies, and overall patient management.This research was supported by PNRR-MUR-M4C2 PE0000006 Research Program “MNESYS”—A multiscale integrated approach to the study of the nervous system in health and disease