Search

The emergence of the precision medicine paradigm in oncology has led to increasing interest in the integration of real-world data (RWD) into cancer clinical research. As sources of real-world evidence (RWE), such data could potentially help address the uncertainties that surround the adoption of novel anticancer therapies into the clinic following their investigation in clinical trials. At present, RWE-generating studies which investigate antitumour interventions seem to primarily focus on collecting and analysing observational RWD, typically forgoing the use of randomisation despite its methodological benefits. This is appropriate in situations where randomised controlled trials (RCTs) are not feasible and non-randomised RWD analyses can offer valuable insights. Nevertheless, depending on how they are designed, RCTs have the potential to produce strong and actionable RWE themselves. The choice of which methodology to employ for RWD studies should be guided by the nature of the research question they are intended to answer. Here, we attempt to define some of the questions that do not necessarily require the conduct of RCTs. Moreover, we outline the strategy of the European Organisation for Research and Treatment of Cancer (EORTC) to contribute to the generation of robust and high-quality RWE by prioritising the execution of pragmatic trials and studies set up according to the trials-within-cohorts approach. If treatment allocation cannot be left up to random chance due to practical or ethical concerns, the EORTC will consider undertaking observational RWD research based on the target trial principle. New EORTC-sponsored RCTs may also feature concurrent prospective cohorts composed of off-trial patients. ispartof: EUROPEAN JOURNAL OF CANCER vol:186 pages:52-61 ispartof: location:England status: published

Background The MHRA Innovative Licensing Access Pathway (ILAP) is a project designed to provide new medicines with a quicker route through the regulatory system and thus to patients. Public and patient involvement in ILAP was established by MHRA through a Public and Patient Reference Group (PPRG). This was done prior to publication of its PPI Strategy and ILAP is included in that Strategy. What Happened The PPRG was established within the ILAP programme to advise on patient engagement within the ILAP process. Some members also volunteered to attend meetings of the Steering Group from mid-2021 and took part in the review of pharmaceutical company applications for entry to ILAP. Over the course of two years, as the ILAP programme was extended, the number of the involved members fell, while experience grew and the input of those remaining became more valued. At the same time the MHRA was developing its PPI strategy and looking for ways to address the challenge of involvement across the considerable breadth of its activities. Conclusion Public and patient involvement in the ILAP project has been positive, facilitated by MHRA staff and their colleagues from ILAP partner organisations. Patients’ knowledge and experience from their previous involvement in medicines development and other research has contributed to the ILAP process. It has clearly demonstrated that experienced patient advocates can address issues which lie outside their personal ‘lived experience’ and which may also be innovative and scientifically challenging. However, the corporate communication with PPRG members has been variable. Members of the group were not consulted when MHRA reviewed the ILAP programme or included in discussions about the future of patient involvement in ILAP or later successor programmes. Decisions on other factors, such as whether patient advocates should be paid for their time, as is the case in other agencies, have been deferred.

Purpose This paper aims to offer practical suggestions as to factors needing consideration when meeting, interacting with or assessing the needs of an older person living with acquired deafblindness. Design/methodology/approach The paper’s author draws on his personal experience of living with acquired deafblindness to offer practical suggestions. Findings This paper offers an experiential definition of acquired deafblindness, before providing practical suggestions related to engaging with deafblind people, distinguishing between acquired deafblindness and cognitive decline, and assessing hearing and sight levels. Originality/value There is a paucity of literature on the lived experience of older people living with acquired deafblindness. This paper offers both a unique insight into this experience combined with practical suggestions for those in contact with older deafblind people.

The global demand for hospital treatment exceeds capacity.The COVID-19 pandemic has exacerbated this issue, leading to increased backlogs and longer wait times for patients. The amount of outpatient attendances undertaken in many settings is still below pre-pandemic levels and this, combined with delayed referrals, means that patients are facing delays in treatment and poorer health outcomes. Use of digital health technologies, notably the use of remote symptom monitoring systems based on patient-reported outcomes (PROs), may offer a solution to reduce outpatient waiting lists and tailor care to those in greatest need. Drawing on international examples, the authors explore the use of electronic PRO systems to triage clinical care. We summarise the key benefits of the approach and also highlight the challenges for implementation, which need to be addressed to promote equitable healthcare delivery.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course characterized by pre-motor, non-motor and motor symptoms, which negatively impact the quality of life of patients and cause high health care costs. Therefore, the present study aims to discuss the clinical manifestations of PD and to make a correlation with the gut-brain (GB) axis, approaching epidemiology and therapeutic perspectives, to better understand its clinical progression and identify symptoms early. A literature review was performed regarding the association between clinical progression, the gut-brain axis, epidemiology, and therapeutic perspectives, in addition to detailing pre-motor, non-motor symptoms (neuropsychiatric, cognitive, autonomic, sleep disorders, sensory abnormalities) and cardinal motor symptoms. Therefore, this article addresses a topic of extreme relevance, since the previously mentioned clinical manifestations (pre-motor and non-motor) can often act as prodromal markers for the early diagnosis of PD and may precede it by up to 20 years.

Randomized clinical trials are critical for evaluating the safety and efficacy of interventions in oncology and informing regulatory decisions, practice guidelines, and health policy. Patient-reported outcomes (PROs) are increasingly used in randomized trials to reflect the impact of receiving cancer therapies from the patient perspective and can inform evaluations of interventions by providing evidence that cannot be obtained or deduced from clinicians’ reports or from other biomedical measures. This commentary focuses on how PROs add value to clinical trials by representing the patient voice. We employed 2 previously published descriptive frameworks (addressing how PROs are used in clinical trials and how PROs have an impact, respectively) and selected 9 clinical trial publications that illustrate the value of PROs according to the framework categories. These include 3 trials where PROs were a primary trial endpoint, 3 trials where PROs as secondary endpoints supported the primary endpoint, and 3 trials where PROs as secondary endpoints contrast the primary endpoint findings in clinically important ways. The 9 examples illustrate that PROs add valuable data to the care and treatment context by informing future patients about how they may feel and function on different treatments and by providing clinicians with evidence to support changes to clinical practice and shared decision making. Beyond the patient and clinician, PROs can enable administrators to consider the cost-effectiveness of implementing new interventions and contribute vital information to policy makers, health technology assessors, and regulators. These examples provide a strong case for the wider implementation of PROs in cancer trials.

IntroductionPostoperative radiological surveillance following primary resection of a soft tissue sarcoma (sarcoma of the retroperitoneum, abdomen, pelvis, trunk or extremities) is standard of care in all international high-volume sarcoma centres in the world. The intensity of postoperative surveillance imaging is highly varied and knowledge of the impact of surveillance and surveillance intensity on patients’ quality of life is limited. The aim of this systematic review is to summarise the experiences of patients and their relatives/caregivers of postoperative radiological surveillance following resection of a primary soft tissue sarcoma and its impact on their quality of life.Methods and analysisWe will systematically search MEDLINE, EMBASE, PsycINFO, CINAHL Plus and Epistemonikos. Hand searching of reference lists of included studies will be conducted. Further searches will be performed via Google Scholar, to reveal further studies within unpublished ‘grey’ literature. Two reviewers will independently screen the titles and abstracts following the eligibility criteria. After retrieval of the full text of the selected studies, the methodological quality will be appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research and the Center for Evidence-Based Management checklist for Critical Appraisal of a Cross-Sectional Study. Data on the study population, relevant themes and conclusions will be extracted from the selected papers, and a narrative synthesis will be conducted.Ethics and disseminationThe systematic review does not require ethics approval. The findings of the proposed work will be published in a peer-reviewed journal and disseminated widely to patients, clinicians and allied health professionals through the Sarcoma UK website, the Sarcoma Patient Advocacy Global Network and the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group. In addition, the outcomes of this research will be presented at national and international conferences.PROSPERO registration numberCRD42022375118.

PURPOSE Many patients with cancer, often those with rare cancers such as sarcomas, travel long distances to access expert care. The COVID-19 pandemic necessitated widespread changes in delivery of cancer care, including rapid adoption of telemedicine-based care. We aimed to evaluate the impact of telemedicine on patients, clinicians, and care delivery at the Royal Marsden Hospital (RMH) Sarcoma Unit during the pandemic. METHODS Data were extracted from patient records for all planned outpatient appointments at the RMH Sarcoma Unit from March 23 to April 24, 2020. Patients and clinicians completed separate questionnaires to understand their experiences. RESULTS Of 379 planned face-to-face appointments, 283 (75%) were converted to telemedicine. Face-to-face appointments remained for patients who needed urgent start of therapy or performance status assessment. Patients lived on average > 1.5 hours from RMH. Patient satisfaction (n = 108) with telemedicine was high (mean, 9/10), and only 48% (n = 52/108) would not want to hear bad news using telemedicine. Clinicians found telemedicine efficient, with no associated increased workload, compared with face-to-face appointments. Clinicians indicated lack of physical examination did not often affect care provision when using telemedicine. Most clinicians (n = 17; 94%) believed telemedicine use was practice changing; congruently, 80% (n = 86/108) of patients desired some telemedicine as part of their future care, citing reduced cost and travel time. CONCLUSION Telemedicine can revolutionize delivery of cancer care, particularly for patients with rare cancers who often live far away from expert centers. Our study demonstrates important patient and clinician benefits; assessment of longer-term impact on patient outcomes and health care systems is needed.

Relato do casoMulher, 32 anos, relata dor abdominal intensa (EVA) 9-10, pior dor da vida, tipo cólica em região mesogástrica que irradia para todo o abdômen há 6 meses. Foi submetida à apendicectomia e colecistectomia decorrente do quadro, após isso foi diagnosticada com (AIP), relata terapias com imunomoduladores e uso de morfina em bomba de infusão numa dose de 100mg/dia há 3 meses. Em crise de dor abdominal intensa foi internada e passado um cateter peridural com morfina durante 5 dias, com boa evolução e implantação do dispositivo de fármaco com melhora significativa na 1a semana com (EVA) de 2-3. Em 1 mês, a paciente subiu a escala de dor, foi aumentada a dose, sem melhora. Foi dado morfina e bupivacaina e a (EVA) foi para 2-1 em 6 meses.ComentáriosPorfiria aguda intermitente é uma doença causada pelo acúmulo de Ác. Delta-aminolevulínico e Porfobilinogênio causa sintomas semelhantes ao Abdômen Agudo. Os sintomas se dão em fases de crises, sendo mais comum a dor abdominal intensa que, erroneamente, pode ser considerada necessária a intervenção cirúrgica. A dificuldade do diagnóstico ocorre pois os sintomas são parecidos ao de abdômen agudo, além do desconhecimento da patologia por muitos médicos, logo, faz-se necessário exames laboratoriais, sendo o mais utilizado o EAS. O tratamento convencional é feito com o uso de heme administrado (EV), além do uso, principalmente, da morfina para o controle das crises, podendo utilizá-la através da bomba de infusão intratecal, no caso de dores crônicas.Os principais efeitos colaterais dos opióides são: obstipação, coceira, convulsões, vômitos e bradipnéia.Conclusão Tendo em vista que a paciente obteve melhora após o uso da bomba de infusão intratecal com morfina e bupivacaina a (EVA) de 9-10 foi para 1-2 em um tempo de 6 meses. Em contraste, o uso somente de morfina em bomba de infusão intratecal teve a recidiva em 1 mês do quadro de dor, mesmo com o aumento da dose. Viu-se que, o efeito sinérgico do uso da bomba de infusão intratecal com morfina associado à bupivacaina para o controle de dores crônicas na (PAI) obteve maior eficácia. O caso mostrou uma boa resposta ao tratamento, mas é necessário promover mais estudos para esclarecer o tema. Palavras-chave: Porfiria aguda intermitente, Bomba de Infusão Intratecal e tratamento de porfiria intermitente aguda.

IntroductionThe use of electronic patient-reported outcome (ePRO) systems to capture PRO data in clinical trials is increasing; however, their feasibility, acceptability and utility in clinical trials of advanced therapy medicinal products (ATMPs) are not yet well understood. This protocol describes a qualitative study that aims to evaluate the feasibility and acceptability of ePRO data capture using a trial-specific ePRO system (the PROmics system) within an advanced therapy trial involving patients with immune-mediated inflammatory disease (rheumatoid arthritis, lupus, primary sclerosing cholangitis (PSC) and Crohn’s disease).Methods and analysisThis protocol for a remote, qualitative, interview-based feasibility study is embedded within the POLARISE trial, a single-arm, phase II, multisite ATMP basket trial in the UK. 10–15 patients enrolled in the POLARISE trial and 10–15 research team members at the trial sites will be recruited. Participants will take part in semistructured interviews which will be transcribed verbatim and analysed thematically according to the framework method. Data collection and analysis will occur concurrently and iteratively. Researcher triangulation will be used to achieve a consensus-based analysis, enhancing rigour and trustworthiness.Ethics and disseminationThis study was approved by the London—West London and GTAC Research Ethics Committee (Ref: 21/LO/0475). Informed consent will be obtained from all participants prior to data collection. The study findings will be published in peer-review journals and disseminated via conference presentations and other media. Our patient and public involvement and engagement group and ATMP stakeholder networks will be consulted to maximise dissemination and impact.Trial registration numberISRCTN80103507.

Patient and public involvement in research helps to make it more relevant and useful to the end-users. Involvement influences the design, delivery and dissemination of research, ultimately leading to better services, treatments and care. Researchers are therefore keen to involve patients, carers and public in their work, but are sometimes uncertain about who to involve. Some confusion may arise from the terms used. The UK’s catch-all term ‘patient and public involvement’ suggests this is a single activity, that perhaps both ‘patient’ and ‘public’ input are needed, or that either will do. The terms ‘patient’, ‘carer’ and ‘public’ have been defined, but are not used consistently. In fact there are many different contexts for involvement and many different kinds of decisions made, which then determine whose input will be most valuable. Clarity about the ‘why’ can help answer the ‘who’ question. However, not all researchers are clear about the purpose of involvement. While it is often understood to have a moral purpose, or to improve research quality, this doesn’t always identify who needs to be involved. When learning is understood to be the purpose of involvement, then the most appropriate people to involve are those with relevant experiential knowledge. In research projects, these are people with lived experience of the topic being investigated. This could be patients, carers, members of the public or health professionals. In this article we discuss how involving people who do not have the relevant experiential ‘lived’ knowledge may contribute to ineffective or tokenistic involvement. These people are as likely as researchers to make assumptions, risking missing key insights or resulting in outcomes that are off-putting or even harmful to research participants. We conclude that greater attention needs to be given to the question of who to involve. Raising awareness of the significance of experiential knowledge and the contextual factors that determine whose input will be most useful will help everyone to understand their roles and improve the quality of involvement. It will help to maximise the opportunities for learning, increasing the likelihood of impact, and helping to achieve the ultimate goal of improved health and services., Plain English summary Patient and public involvement in research helps to make it more relevant and useful to the end-users. Researchers are therefore keen to involve people but are sometimes uncertain about who to involve. Some confusion comes from the terms used. The UK’s term ‘patient and public involvement’ suggests there is only one activity and that both inputs are needed or either will do. The terms ‘patient’, ‘carer’ and ‘public’ are not used in the same way by everyone. Involvement happens in many different situations, influencing different kinds of decisions, which then determines whose input will be most valuable. Being clear about the ‘why’ can help answer the ‘who’ question. However, not all researchers are clear about the purpose of involvement. When learning is understood to be the purpose, the most appropriate people to involve are those with relevant experiential knowledge. They provide insights based on their lived experience. In research projects, this is experience of the topic being studied. This could be patients, carers, public or health professionals. We discuss how involving people who do not have relevant experiential knowledge may limit impact. These people may be as likely as researchers to make wrong assumptions. This risks missing key insights or making unhelpful decisions. We conclude that greater attention should be given to the question of who to involve. Raising awareness of the importance of relevant experiential knowledge and other factors that determine whose input will be most useful, will help maximise opportunities for learning and increase the potential for impact.

Objectives(a) To adapt the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-patient-reported outcome (PRO) Extension guidance to a user-friendly format for patient partners and (b) to codesign a web-based tool to support the dissemination and uptake of the SPIRIT-PRO Extension by patient partners.DesignA 1-day patient and public involvement session.ParticipantsSeven patient partners.MethodsA patient partner produced an initial lay summary of the SPIRIT-PRO guideline and a glossary. We held a 1-day PPI session in November 2019 at the University of Birmingham. Five patient partners discussed the draft lay summary, agreed on the final wording, codesigned and agreed the final content for both tools. Two additional patient partners were involved in writing the manuscript. The study compiled with INVOLVE guidelines and was reported according to the Guidance for Reporting Involvement of Patients and the Public 2 checklist.ResultsTwo user-friendly tools were developed to help patients and members of the public be involved in the codesign of clinical trials collecting PROs. The first tool presents a lay version of the SPIRIT-PRO Extension guidance. The second depicts the most relevant points, identified by the patient partners, of the guidance through an interactive flow diagram.ConclusionsThese tools have the potential to support the involvement of patient partners in making informed contributions to the development of PRO aspects of clinical trial protocols, in accordance with the SPIRIT-PRO Extension guidelines. The involvement of patient partners ensured the tools focused on issues most relevant to them.

Introduction Repeat laboratory testing is often necessary in hospitals. However, frequent blood draws can be harmful to older patients. The objective of this study was to identify the most frequently ordered laboratory tests and repeat testing rates for these tests among older inpatients. Methods A retrospective observational study of inpatients of age 80 years and over in 4 public hospitals in New South Wales, Australia, was conducted between 2008 and 2013. Proportions of laboratory tests and proportions of repeated tests among the most frequently used tests were reported. Results There were 42739 patients with 108003 admissions (56.2% women; 43.2% of ages 80–84). Of these admissions, 95.9% had a laboratory test, with 3012577 tests recorded. Five tests accounted for 62% of all tests and were present in 98.5% of admissions: electrolytes urea and creatinine (EUC; 18% of all tests ordered), complete blood count (CBC; 16.7%), calcium magnesium phosphate (CaMgPhos; 10.2%), liver function test (LFT; 9.0%), and C-reactive protein (CRP; 8.0%). Proportions of repeat tests for this group performed outside recommended minimum repeat intervals were 10.3% EUC, 8.9% CBC, 41.5% CRP, 68.2% CaMgPhos, and 65.2% LFT tests. An exponential increase in repeat testing for all 5 tests was observed around 24 h after a previous test. Conclusion Compliance with guidelines on repeat testing intervals among older patients is variable. A better understanding of the underlying reasons for repeat testing would allow targeting of interventions, including decision support, to improve laboratory use for older inpatients.

To compare flexible distal-chip laryngoscopy (FDL) and rigid telescopic laryngoscopy (RTL) in image quality and diagnostic ability.Prospective cohort study; blinded comparison.Eighteen normal adult subjects were recruited to undergo both FDL and RTL and normalized videos were recorded. Three blinded laryngologists compared the videos for color fidelity, illumination, resolution, and vascularity, and indicated superiority with FDL, RTL, or no difference. Raters also reported if an abnormality was seen and in which video it was better visualized. Videos for two subjects were repeated to assess intra-rater reliability, making 20 video comparisons across 3 raters for a total of 60 ratings. Differences in responses were analyzed via Mann-Whitney U and Pearson ΧRTL was rated superior in all categories of image quality (47 vs 5 vs 8, P0.01; 47 vs 7 vs 6, P0.01; 51 vs 5 vs 4, P0.01; 44 vs 9 vs 7, P0.01, respectively). An abnormality was seen 33 times with both modalities and 6 times with RTL only. When seen with both modalities, visualization was superior in RTL compared with FDL (29 vs 4, P0.01).There was significant superiority of RTL in all categories of image quality, with slight inter-rater agreement for color fidelity, resolution, and vascularity. RTL was also significantly better for visualization of abnormalities. These findings suggest superior image quality in RTL compared with FDL, but further research is required to determine if this difference is clinically significant.

Importance Patient-reported outcomes (PROs) can inform healthcare decisions, regulatory decisions, and healthcare policy, and also can be used for audit/benchmarking and to monitor symptoms and provide timely care tailored to individual needs. However, several ethical issues have been raised in relation to PRO use. Objective To develop an international, consensus-based, PRO-specific ethical guidelines for clinical research.Evidence ReviewThe PRO ethics guidelines were developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network’s guideline development framework. This included a systematic review of the ethical implications of PROs in clinical research. The databases MEDLINE (Ovid), EMBASE, AMED and CINAHL were searched from inception until May 2020. The keywords ‘patient reported outcome*’ and ‘ethic*’ were used to search the databases. Two reviewers independently conducted title and abstract screening before full-text screening to determine eligibility. The review was supplemented by the SPIRIT-PRO Extension recommendations for trial protocol. Subsequently, a two-round international Delphi process (n=96 participants; May and August 2021) and a consensus meeting (n=25 international participants; October 2021) were held. Prior to voting, consensus meeting participants were provided with a summary of the Delphi process results and information on whether the items aligned with existing ethical guidance.Findings Twenty-three items were considered in the first round of the Delphi process: six relevant candidate items from the systematic review and seventeen additional items drawn from the SPIRIT-PRO Extension. Ninety-six international participants voted on the relevant importance of each item for inclusion in ethical guidelines and twelve additional items were recommended for inclusion in round 2 of the Delphi (35 items in total). Fourteen items were recommended for inclusion at the consensus meeting (n=25 participants). The final wording of the PRO ethical guidelines was agreed by consensus meeting participants with input from six additional individuals. Included items focused on PRO-specific ethical issues relating to research rationale, objectives, eligibility requirements, PRO concepts/domains, PRO assessment schedules, sample size, PRO data monitoring, barriers to PRO completion, participant acceptability and burden, administration of PRO questionnaires for participants who are unable to self-report PRO data, input on PRO strategy by patient partners or members of the public, avoiding missing data and dissemination plans. Conclusions and Relevance The PRO ethics guidelines provide recommendations for ethical issues that should be addressed in PRO clinical research. Addressing ethical issues of PRO clinical research has the potential to ensure high-quality PRO data while minimising participant risk, burden and harm and protecting participant and researcher welfare.