GCT-61. CORRELATION OF PATTERNS OF DISEASE RECURRENCE WITH RADIOTHERAPY TECHNIQUES AND DOSE IN INTRACRANIAL GERM CELL TUMOURS (icGCT): LESSONS FROM THE UK COHORT OF SIOP GCT96 STUDY

Abstract BACKGROUND There are global variations in radiotherapy approaches for icGCT. An understanding of patterns of disease recurrence correlated with radiation techniques and doses is important in standardising and improving the quality of radiotherapy using high-precision techniques. METHODS AND RESULTS Data from 20 patients with tumour recurrence after treatment within the SIOP GCT96 study in the UK were analysed. Seven (35%) patients had germinoma and 13 (65%) had non-germinoma. Twelve patients had local recurrence, 5 had metastatic and 3 had local and metastatic disease. Radiotherapy details were retrieved in only 8 patients (40%). Six patients had received focal radiotherapy and two craniospinal radiotherapy. Of the patients who received focal radiotherapy, 4 had recurrence within the radiation portal, one had periventricular recurrence and one had marker-positive recurrence with no radiological lesions. Both patients who received CSI recurred within the CSF space. The main reasons for poor retrieval of treatment details were difficulty in retrieving archived information and that the study was conducted during a period before PACS or electronic radiotherapy records. CONCLUSION This study highlights the importance prospective data collection and analysis to understand the patterns of recurrence in icGCT. Even within a prospective study, radiotherapy techniques varied between centres. There is therefore an urgent need for centralised radiological review and prospective radiotherapy quality assurance measures in future clinical trials.

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National control laboratory independent lot testing of COVID-19 vaccines: the UK experience

npj Vaccines ◽

10.1038/s41541-021-00368-7 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Nicola J. Rose ◽

Paul Stickings ◽

Silke Schepelmann ◽

Marc J. A. Bailey ◽

Chris Burns

Keyword(s):

Clinical Trials ◽

Vaccine Development ◽

Regulatory Approval ◽

Safety Measures ◽

Discovery Research ◽

Innovative Products ◽

The Uk ◽

Vaccine Availability ◽

And Control

AbstractThe past 18 months have seen an unprecedented approach to vaccine development in the global effort against the COVID-19 pandemic. The process from discovery research, through clinical trials and regulatory approval often takes more than 10 years. However, the critical need to expedite vaccine availability in the pandemic has meant that new approaches to development, manufacturing, and regulation have been required: this has necessitated many stages of product development, clinical trials, and manufacturing to be undertaken in parallel at a global level. Through the development of these innovative products, the world has the best chance of finding individual, or combinations of, vaccines that will provide adequate protection for the world’s population. Despite the huge scientific and regulatory achievements and significant investment to accelerate vaccine availability, it is essential that safety measures are not compromised. Here we focus on the post regulatory approval testing by independent laboratories that provides an additional assurance of the safety and quality of a product, with an emphasis on the UK experience through the National Institute for Biological Standards and Control (NIBSC), an expert centre of the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

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PAciFy Cough – A multicentre, double blind, placebo controlled, crossover trial of morphine sulfate for the treatment of PulmonAry Fibrosis Cough

10.21203/rs.3.rs-508775/v1 ◽

2021 ◽

Author(s):

Zhe Wu ◽

Winston Banya ◽

Nazia Chaudhuri ◽

Ira Jakupovic ◽

Toby Maher ◽

...

Keyword(s):

Quality Of Life ◽

Clinical Trials ◽

Pulmonary Fibrosis ◽

Crossover Trial ◽

Randomised Trial ◽

Morphine Sulfate ◽

Double Blind ◽

Double Blind Placebo ◽

The Uk

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease that leads to lung scarring, Cough is reported by 85% of patients with IPF and can be a distressing symptom with a significant impact on patients’ quality of life. There are no proven effective therapies for IPF related cough. While morphine is frequently used as a palliative agent for breathlessness in IPF, its effects on cough have never been tested. PAciFy Cough is a multicenter, double-blind, placebo-controlled, crossover trial of morphine sulfate for the treatment of cough in IPF. Methods: We will recruit 44 subjects with IPF prospectively from three interstitial lung disease units in the UK, namely the Royal Brompton Hospital, Manchester University NHS Foundation Trust (MFT) and Aintree University Hospital NHS Foundation Trust. Patients will be randomized (1:1) to either placebo twice daily or morphine sulfate 5mg twice daily for 14 days. They will then crossover after a 7 day washout period. The primary endpoint is the percent change in daytime cough frequency (coughs per hour) from baseline as assessed by objective cough monitoring at Day 14 of treatment.Discussion: This multicentre, randomised trial will assess the effect of opioids on cough counts and cough associated quality of life in IPF subjects. If proven to be an effective intervention, it represents a readily available treatment for patients.Trial registration: The study was approved by the UK Medicines and Healthcare Regulatory Agency (Ref: CTA 21268/0224/001-0001 – EUDRACT 2019-003571-19 – Protocol Number RBH2019/001) on 08 April 2020, in compliance with the European Clinical Trials Directive and the Medicines for Human Use (Clinical Trials) Regulations 2004 and its subsequent amendments. The study was provided with ethical approval by the London Brent Research Ethics Committee (Ref: 20/LO/0368) on 21 May 2020 and is registered with clinicaltrials.gov (NCT04429516) on 12 June 2020, available at https://clinicaltrials.gov/ct2/show/NCT04429516

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O-065 Evaluating quality of life (QL) and patient reported outcomes(PROs) in non-small cell lung cancer (NSCLC): A prospective study using a hand-held computerized form of the validated LCSS instrument in clinical trials and in clinical practice

Lung Cancer ◽

10.1016/s0169-5002(05)80197-7 ◽

2005 ◽

Vol 49 ◽

pp. S25

Author(s):

P. Hollen ◽

R. Gralla ◽

P. Kuruvilla ◽

J. Meharchand ◽

H. Solow ◽

...

Keyword(s):

Quality Of Life ◽

Lung Cancer ◽

Clinical Trials ◽

Clinical Practice ◽

Patient Reported Outcomes ◽

Small Cell ◽

Small Cell Lung ◽

Patient Reported ◽

A Prospective Study

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The multi-disciplinary meeting as a tool to identify patients for clinical trials and translational research.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e14001 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e14001-e14001

Author(s):

H Winter ◽

David Rea

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Translational Research ◽

Solid Tumour ◽

Outcome Data ◽

Team Meetings ◽

Proactive Approach ◽

The Uk

e14001 Background: Cancer multi-disciplinary team meetings (MDTs) were established with one of the core aims to increase participation in clinical research. However, a recent Cancer Research UK study observing 624 patient MDT discussions revealed only 8 (1.3%) patients included a discussion on clinical trials. Current work in the UK looking at MDT effectiveness has explored the quality of discussions and team dynamics. However, recruitment to clinical trials has not been promoted as an indicator of an effective MDT. This study explored the role of MDTs in identifying patients for research across all solid tumour MDTs in a tertiary cancer centre. Methods: This study explored the outcome data from solid tumour MDTS; reports on the observation of solid tumour MDTs and completion of a trials and translational proforma about patient discussions on research; exploration of MDT members views on the role of MDTS in identifying opportunities for patients to participate in clinical trials and translational research. Results: MDT outcomes from all solid tumour MDTs were reviewed. Out of 7000 local MDT outcomes from Avon Cancer Registry April 2019- Set 2019. Only 409 discussions included an outcome registered with “Clinical Trial y/n” (5%). In the majority there was no mention of any consideration of clinical trial or an explicit trial documented. Conclusions: We report on the exploration of the MDT as integral to identifying patients for clinical trials and translational research. This requires input and buy in from MDT members and the identification of research champions attending MDTs. The integration of genomics data into MDTs will require a proactive approach to access clinical trials for patients with identified potential actionable targets.

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A survey of the feasibility of developing osteoporosis clinical trials in Duchenne muscular dystrophy: Survey of the opinion of young people with Duchenne muscular dystrophy, families and clinicians

Clinical Trials ◽

10.1177/1740774520958395 ◽

2020 ◽

pp. 174077452095839

Author(s):

Sze Choong Wong ◽

Shuko Joseph ◽

Nadia Capaldi ◽

Marina Di Marco ◽

Jennifer Dunne ◽

...

Keyword(s):

Clinical Trials ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Young People ◽

Outcome Measures ◽

Bone Health ◽

Limited Evidence ◽

Great Awareness ◽

The Uk

Background/aims Given the extent of osteoporosis in people with Duchenne muscular dystrophy treated with glucocorticoids and the limited evidence of bone-protective therapies, clinical trials are needed. We conducted surveys to obtain the opinion of young people with Duchenne muscular dystrophy, parents/guardians and neuromuscular clinicians on the feasibility of osteoporosis clinical trials in this population. Methods Online surveys were sent to three groups: (a) people with a confirmed diagnosis of Duchenne muscular dystrophy (≥14 years), (b) parents and guardians and (c) neuromuscular clinicians in the UK NorthStar Clinical Network. Surveys (a) and (b) were distributed via the UK Duchenne muscular dystrophy Registry. Results Survey respondents included 52 people with Duchenne muscular dystrophy with a median age of 17 years (range: 14, 40) and 183 parents/guardians. Fourteen out of 23 (61%) NorthStar centres responded. Of the 52 people with Duchenne muscular dystrophy, 13 (25%) were very concerned about their bone health and 21 (40%) were slightly concerned. Of the 183 parents/guardians, 75 (41%) were very concerned about their son’s bone health and 90 (49%) were slightly concerned. Fractures and quality of life were the top two main outcome measures identified by people with Duchenne muscular dystrophy. Fractures and bone density were the top two main outcome measures identified by parents/guardians and neuromuscular clinicians. Thirty percent of people with Duchenne muscular dystrophy and 40% of parents/guardians would not take part if an osteoporosis trial involved a placebo that was administered parenterally. Only 2 of the 14 NorthStar centres (14%) would enrol people with Duchenne muscular dystrophy if a parenteral placebo was used in an osteoporosis trial in Duchenne muscular dystrophy. Conclusion There is great awareness of bone health and the need for bone-protective trials among people with Duchenne muscular dystrophy and their carers. However, a proportion of people with Duchenne muscular dystrophy and parents are reluctant to participate in a placebo-controlled osteoporosis trial that included a parenteral therapy. A larger proportion of health care experts are unwilling to enrol their patients in such a trial. Our finding is relevant for the design of bone-protective studies in Duchenne muscular dystrophy.

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Treatments for dry age-related macular degeneration and Stargardt disease: a systematic review

Health Technology Assessment ◽

10.3310/hta22270 ◽

2018 ◽

Vol 22 (27) ◽

pp. 1-168 ◽

Cited By ~ 15

Author(s):

Norman Waugh ◽

Emma Loveman ◽

Jill Colquitt ◽

Pamela Royle ◽

Jian Lee Yeong ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Visual Loss ◽

Age Related Macular Degeneration ◽

Stargardt Disease ◽

Short Term ◽

Age Related ◽

Dry Amd ◽

The Uk

Background Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. Objective To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Design Systematic review. Methods We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. Results The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or governments. Limitations In AMD, the main limitation came from the poor quality of much of the evidence. Many studies used VA as their main outcome despite not having sufficient duration to observe changes. The evidence on treatments for STGD is sparse. Most studies tested interventions with no comparison group, were far too short term, and the quality of some studies was poor. Future work We think that the topics on which the Health Technology Assessment (HTA) and Efficacy Mechanism and Evaluation (EME) programmes might consider commissioning primary research are in STGD, a HTA trial of fenretinide (ReVision Therapeutics, San Diego, CA, USA), a visual cycle inhibitor, and EME research into the value of lutein and zeaxanthin supplements, using short-term measures of retinal function. In AMD, we suggest trials of fenretinide and of a potent statin. There is epidemiological evidence from the USA that the drug, levodopa, used for treating Parkinson’s disease, may reduce the incidence of AMD. We suggest that similar research should be carried out using the large general practice databases in the UK. Ideally, future research should be at earlier stages in both diseases, before vision is impaired, using sensitive measures of macular function. This may require early detection of AMD by screening. Study registration This study is registered as PROSPERO CRD42016038708. Funding The National Institute for Health Research HTA programme.

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Setting up non-commercial clinical trials takes too long in the UK: findings from a prospective study

Journal of the Royal Society of Medicine ◽

10.1258/jrsm.2008.070373 ◽

2008 ◽

Vol 101 (6) ◽

pp. 299-304 ◽

Cited By ~ 19

Author(s):

Allan Hackshaw ◽

Hannah Farrant ◽

Sue Bulley ◽

Michael J Seckl ◽

Jonathan A Ledermann

Keyword(s):

Clinical Trials ◽

Prospective Study ◽

The Uk ◽

A Prospective Study

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An assessment of the NAVIFY clinical trial match application using clinical simulation-based research methods.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13552 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13552-e13552

Author(s):

Matthew Stewart Prime ◽

Chaohui Guo ◽

Gianluca Fontana ◽

Saira Ghafur ◽

Jack Halligan ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Objective Measure ◽

Mental Effort ◽

Postal Code ◽

Cancer Clinical Trials ◽

Eligibility Criteria ◽

Before And After ◽

The Uk

e13552 Background: Cancer clinical trials require matching patients to strict, and sometimes lengthy, eligibility criteria. NAVIFY Clinical Trial Match (CTM) is a digital solution that uses data on an individual patient’s condition, genomic alterations and institution’s postal code to automatically find suitable clinical trials. We assessed the efficiency, accuracy and cognitive burden of NAVIFY CTM on matching patients to cancer clinical trials in the UK. Methods: 10 clinicians (8 medical doctors, 2 clinical trial practitioners) participated. Synthetic patient cases were developed with input from two oncologists, a histopathologist and a radiologist. Participants were instructed to identify appropriate trials for five patients using the NAVIFY CTM and five patients with the legacy approach (i.e. online trial databases) within one hour. For each method, participants were advised to approach the exercise with the level of scrutiny employed in a normal clinical setting. The efficiency, quality, and cognitive burden of trial matching was measured for each participant. The quality of trial matches was independently scored by an oncologist who did not participate in the simulations. The cognitive burden was measured subjectively, via a single-item questionnaire used to measure mental effort (Paas scale), and objectively, via Stroop test before and after each method. A survey was also conducted. Results: Efficiency: Participants completed the trial matching more efficiently using NAVIFY CTM, with trial matches completed on average one minute and 42 seconds faster using the digital solution (n = 73 matches) compared with the most commonly used online trial database, ClinicalTrials.gov (n = 52). Participants were more likely to ‘completely agree’ that they had enough time to complete the task using the NAVIFY CTM (70%) compared to online trial databases (40%). Quality of the matches: On the survey, more participants reported that trial suggestions were ‘mostly relevant’ for NAVIFY CTM (70%) compared with ClinicalTrials.gov (30%). The quality of trial matches was the same for both methods (as scored independently by an oncologist). Cognitive burden: On the subjective measure of cognitive burden, more participants required ‘low’ or ‘rather low’ mental effort to use NAVIFY CTM (50%) compared to online trial databases (7%). On the objective measure, there is a seemingly less pronounced Stroop effect (often interpreted as higher mental agility) using NAVIFY CTM vs. legacy approach. Conclusions: Preliminary findings suggest that, compared to online trial databases, the NAVIFY CTM can reduce the amount of time to match patients to clinical trials, provide more relevant trial suggestions, and decrease self-reported mental effort for the decision-maker.

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Coping Style in Glioma Patients and Their Caregiver: Evaluation During Disease Trajectory

Frontiers in Neurology ◽

10.3389/fneur.2021.709132 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lara Guariglia ◽

Sonia Ieraci ◽

Veronica Villani ◽

Antonio Tanzilli ◽

Dario Benincasa ◽

...

Keyword(s):

Quality Of Life ◽

Psychological Distress ◽

Coping Strategies ◽

Coping Style ◽

Performance Status ◽

Disease Recurrence ◽

Fighting Spirit ◽

Short Period ◽

A Prospective Study

Background: Patients with glioma have a poor prognosis and, in a short period of time, have to deal with severe forms of disability, which compromise their psychological distress and quality of life. The caregivers of these patients consequently carry a heavy burden in terms of emotional and patient care. The study aims to evaluate the coping strategies of patients and their caregivers during the course of the disease in order to frame the adaptation process in a rapidly progressing pathology.Methods: A prospective study on 24 dyads of patients affected by malignant glioma and their caregivers was conducted between May 2016 and July 2018. Questionnaires designed to identify the coping style (MINI-MaC Scale) and psychological distress (HADS scores) and assess QOL (EQ-5D) were administered at two time points: at first lines of treatment and at disease recurrence.Results: Patients and their caregiver structure adaptive coping strategies during the disease: a coping style oriented toward a fighting spirit prevails at baseline (Mini-Mac Mean 3.23); fatalism prevails at recurrence (Mini-Mac Mean 3.03). Psychological distress affects the coping style expressed: high levels of anxiety symptoms were found to be significantly associated with a coping style oriented toward anxious preoccupation, helpless–hopeless, and fatalism; low depressive symptoms were inversely correlated with fighting spirit coping style. Patients' and caregivers' perceptions of quality of life were correlated between them and with performance status assessed by clinicians. In a dyadic perspective, the adaptation of a member of the couple varies as a function of the other partner's coping style.Conclusions: Our data are in line with previous literature on cancer patients, demonstrating that coping style is not a persistent dimension of personality, but can change depending on the situation. Despite the disease rapid course, patients and their caregivers can structure adaptive and functional defenses to manage the disease.

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