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Annmarie Nelson - One of the best experts on this subject based on the ideXlab platform.

  • Developing meaningful public involvement in a cancer Clinical Trials Unit
    Trials, 2015
    Co-Authors: Jessica Baillie, Jim Fitzgibbon, Natalie Simon, Annmarie Nelson
    Abstract:

    Background Public involvement in Clinical Trials has developed rapidly and is now expected by funders, research ethics committees, researchers and members of the public. Despite benefitting the research, researchers and public members involved, public involvement can be challenging and tokenistic. For several years, a cancer Clinical Trials Unit (CTU) in Wales, in association with a government funded public involvement organisation, has made serious efforts to meaningfully and appropriately include members of the public across all its Clinical Trials.

  • TACT: Research Partner involvement in a cancer Clinical Trials Unit and academic research centre; evaluating its impact
    Trials, 2015
    Co-Authors: Noreen Hopewell-kelly, Jessica Baillie, Jim Fitzgibbon, Annmarie Nelson
    Abstract:

    Background Since 2005 lay representatives (‘Research Partners’ – RP) have been involved in the work of a Clinical Trials Unit and academic research centre. Their roles can include attending trial management groups, reviewing documents and chairing and presenting at sub-committees. Where recruitment of RPs was once opportunistic, RPs are now more formally recruited in conjunction with a national public involvement organisation. The impact of RPs at the research centre had not been examined in-depth, nor research partners’ or staff members’ experiences been previously explored. The TACT study was conducted to investigate the input and impact of RPs to ensure the best possible working partnership between the centre and the public is achieved.

  • TACT: WHAT IMPACT DOES RESEARCH PARTNER INVOLVEMENT HAVE ON THE WORKING PRACTICES OF A CANCER Clinical TRIAL Unit AND ACADEMIC RESEARCH CENTRE?
    BMJ Supportive & Palliative Care, 2015
    Co-Authors: Noreen Hopewell-kelly, Jessica Baillie, Jim Fitzgibbon, Annmarie Nelson
    Abstract:

    From 2005, lay representatives (‘Research Partners-RPs) have been involved as memebers of the research team in a Clinical Trials Unit, and more recently a Marie Curie facility. However, the impact of their work has not been routinely examined. The TACT study was designed as a means of evaluation.

  • The role of the public in developing interventions: a reflection and critique of a cancer Clinical Trials Unit's model.
    Patient preference and adherence, 2014
    Co-Authors: Jim Fitzgibbon, Jessica Baillie, Natalie Simon, Annmarie Nelson
    Abstract:

    The importance of involving lay representatives in research is well-recognized but is not consistently meaningfully practiced or reported. Although the positive outcomes of lay representative involvement can include more relevant research questions and outcomes, challenges are also apparent, including tokenistic involvement by research teams. A Cancer Research UK-funded and National Cancer Research Institute-registered cancer Clinical Trials Unit in the United Kingdom established a program of work to promote genuine and consistent involvement of lay representatives (or “research partners”) as part of the research team. Furthermore, a volunteer was employed to recruit and coordinate the research partners in partnership with a national agency for public involvement in health and social care research in Wales. This article reports on the development of this project and how it will be formally evaluated. Recommendations for involving lay representatives are also posed.

Mahesh K B Parmar - One of the best experts on this subject based on the ideXlab platform.

  • comparison of aggregate and individual participant data approaches to meta analysis of randomised Trials an observational study
    PLOS Medicine, 2020
    Co-Authors: Jayne F Tierney, Sarah Burdett, David Fisher, Lesley A Stewart, Mahesh K B Parmar
    Abstract:

    Background It remains unclear when standard systematic reviews and meta-analyses that rely on published aggregate data (AD) can provide robust Clinical conclusions. We aimed to compare the results from a large cohort of systematic reviews and meta-analyses based on individual participant data (IPD) with meta-analyses of published AD, to establish when the latter are most likely to be reliable and when the IPD approach might be required. Methods and findings We used 18 cancer systematic reviews that included IPD meta-analyses: all of those completed and published by the Meta-analysis Group of the MRC Clinical Trials Unit from 1991 to 2010. We extracted or estimated hazard ratios (HRs) and standard errors (SEs) for survival from trial reports and compared these with IPD equivalents at both the trial and meta-analysis level. We also extracted or estimated the number of events. We used paired t tests to assess whether HRs and SEs from published AD differed on average from those from IPD. We assessed agreement, and whether this was associated with trial or meta-analysis characteristics, using the approach of Bland and Altman. The 18 systematic reviews comprised 238 unique Trials or trial comparisons, including 37,082 participants. A HR and SE could be generated for 127 Trials, representing 53% of the Trials and approximately 79% of eligible participants. On average, trial HRs derived from published AD were slightly more in favour of the research interventions than those from IPD (HRAD to HRIPD ratio = 0.95, p = 0.007), but the limits of agreement show that for individual Trials, the HRs could deviate substantially. These limits narrowed with an increasing number of participants (p < 0.001) or a greater number (p < 0.001) or proportion (p < 0.001) of events in the AD. On average, meta-analysis HRs from published AD slightly tended to favour the research interventions whether based on fixed-effect (HRAD to HRIPD ratio = 0.97, p = 0.088) or random-effects (HRAD to HRIPD ratio = 0.96, p = 0.044) models, but the limits of agreement show that for individual meta-analyses, agreement was much more variable. These limits tended to narrow with an increasing number (p = 0.077) or proportion of events (p = 0.11) in the AD. However, even when the information size of the AD was large, individual meta-analysis HRs could still differ from their IPD equivalents by a relative 10% in favour of the research intervention to 5% in favour of control. We utilised the results to construct a decision tree for assessing whether an AD meta-analysis includes sufficient information, and when estimates of effects are most likely to be reliable. A lack of power at the meta-analysis level may have prevented us identifying additional factors associated with the reliability of AD meta-analyses, and we cannot be sure that our results are generalisable to all outcomes and effect measures. Conclusions In this study we found that HRs from published AD were most likely to agree with those from IPD when the information size was large. Based on these findings, we provide guidance for determining systematically when standard AD meta-analysis will likely generate robust Clinical conclusions, and when the IPD approach will add considerable value.

  • Changing platforms without stopping the train: experiences of data management and data management systems when adapting platform protocols by adding and closing comparisons
    Trials, 2019
    Co-Authors: Dominic Hague, Stephen Townsend, Lindsey Masters, Mary Rauchenberger, Nadine Van Looy, Carlos Diaz-montana, Melissa Gannon, Nicholas James, Tim Maughan, Mahesh K B Parmar
    Abstract:

    Background There is limited research and literature on the data management challenges encountered in multi-arm, multi-stage platform and umbrella protocols. These trial designs allow both (1) seamless addition of new research comparisons and (2) early stopping of accrual to individual comparisons that do not show sufficient activity. FOCUS4 (colorectal cancer) and STAMPEDE (prostate cancer), run from the Medical Research Council Clinical Trials Unit (CTU) at UCL, are two leading UK examples of Clinical Trials implementing adaptive platform protocol designs. To date, STAMPEDE has added five new research comparisons, closed two research comparisons following pre-planned interim analysis (lack of benefit), adapted the control arm following results from STAMPEDE and other relevant Trials, and completed recruitment to six research comparisons. FOCUS4 has closed one research comparison following pre-planned interim analysis (lack of benefit) and added one new research comparison, with a number of further comparisons in the pipeline. We share our experiences from the operational aspects of running these adaptive Trials, focusing on data management. Methods We held discussion groups with STAMPEDE and FOCUS4 CTU data management staff to identify data management challenges specific to adaptive platform protocols. We collated data on a number of case report form (CRF) changes, database amendments and database growth since each trial began. Discussion We found similar adaptive protocol-specific challenges in both Trials. Adding comparisons to and removing them from open Trials provides extra layers of complexity to CRF and database development. At the start of an adaptive trial, CRFs and databases must be designed to be flexible and scalable in order to cope with the continuous changes, ensuring future data requirements are considered where possible. When adding or stopping a comparison, the challenge is to incorporate new data requirements while ensuring data collection within ongoing comparisons is unaffected. Some changes may apply to all comparisons; others may be comparison-specific or applicable only to patients recruited during a specific time period. We discuss the advantages and disadvantages of the different approaches to CRF and database design we implemented in these Trials, particularly in relation to use and maintenance of generic versus comparison-specific CRFs and databases. The work required to add or remove a comparison, including the development and testing of changes, updating of documentation, and training of sites, must be undertaken alongside data management of ongoing comparisons. Adequate resource is required for these competing data management tasks, especially in Trials with long follow-up. A plan is needed for regular and pre-analysis data cleaning for multiple comparisons that could recruit at different rates and periods of time. Data-cleaning activities may need to be split and prioritised, especially if analyses for different comparisons overlap in time. Conclusions Adaptive Trials offer an efficient model to run randomised controlled Trials, but setting up and conducting the data management activities in these Trials can be operationally challenging. Trialists and funders must plan for scalability in data collection and the resource required to cope with additional competing data management tasks.

  • changing platforms without stopping the train experiences of data management and data management systems when adapting platform protocols by adding and closing comparisons
    Trials, 2019
    Co-Authors: Dominic Hague, Nicholas D. James, Stephen Townsend, Lindsey Masters, Mary Rauchenberger, Melissa Gannon, Tim Maughan, Nadine Van Looy, Carlos Diazmontana, Mahesh K B Parmar
    Abstract:

    There is limited research and literature on the data management challenges encountered in multi-arm, multi-stage platform and umbrella protocols. These trial designs allow both (1) seamless addition of new research comparisons and (2) early stopping of accrual to individual comparisons that do not show sufficient activity. FOCUS4 (colorectal cancer) and STAMPEDE (prostate cancer), run from the Medical Research Council Clinical Trials Unit (CTU) at UCL, are two leading UK examples of Clinical Trials implementing adaptive platform protocol designs. To date, STAMPEDE has added five new research comparisons, closed two research comparisons following pre-planned interim analysis (lack of benefit), adapted the control arm following results from STAMPEDE and other relevant Trials, and completed recruitment to six research comparisons. FOCUS4 has closed one research comparison following pre-planned interim analysis (lack of benefit) and added one new research comparison, with a number of further comparisons in the pipeline. We share our experiences from the operational aspects of running these adaptive Trials, focusing on data management. We held discussion groups with STAMPEDE and FOCUS4 CTU data management staff to identify data management challenges specific to adaptive platform protocols. We collated data on a number of case report form (CRF) changes, database amendments and database growth since each trial began. We found similar adaptive protocol-specific challenges in both Trials. Adding comparisons to and removing them from open Trials provides extra layers of complexity to CRF and database development. At the start of an adaptive trial, CRFs and databases must be designed to be flexible and scalable in order to cope with the continuous changes, ensuring future data requirements are considered where possible. When adding or stopping a comparison, the challenge is to incorporate new data requirements while ensuring data collection within ongoing comparisons is unaffected. Some changes may apply to all comparisons; others may be comparison-specific or applicable only to patients recruited during a specific time period. We discuss the advantages and disadvantages of the different approaches to CRF and database design we implemented in these Trials, particularly in relation to use and maintenance of generic versus comparison-specific CRFs and databases. The work required to add or remove a comparison, including the development and testing of changes, updating of documentation, and training of sites, must be undertaken alongside data management of ongoing comparisons. Adequate resource is required for these competing data management tasks, especially in Trials with long follow-up. A plan is needed for regular and pre-analysis data cleaning for multiple comparisons that could recruit at different rates and periods of time. Data-cleaning activities may need to be split and prioritised, especially if analyses for different comparisons overlap in time. Adaptive Trials offer an efficient model to run randomised controlled Trials, but setting up and conducting the data management activities in these Trials can be operationally challenging. Trialists and funders must plan for scalability in data collection and the resource required to cope with additional competing data management tasks.

  • testing many treatments within a single protocol over 10 years at mrc Clinical Trials Unit at ucl multi arm multi stage platform umbrella and basket protocols
    Clinical Trials, 2017
    Co-Authors: Mahesh K B Parmar, Matthew R. Sydes, Melissa R. Spears, Ruth E Langley, Fay H Cafferty, Babak Choodarioskooei, Louise Brown, Patrick P J Phillips, Sam Rowley, Richard Kaplan
    Abstract:

    There is real need to change how we do some of our Clinical Trials, as currently the testing and development process is too slow, too costly and too failure-prone often we find that a new treatment is no better than the current standard. Much of the focus on the development and testing pathway has been in improving the design of phase I and II Trials. In this article, we present examples of new methods for improving the design of phase III Trials (and the necessary lead up to them) as they are the most time-consuming and expensive part of the pathway. Key to all these methods is the aim to test many treatments and/or pose many therapeutic questions within one protocol.

  • randomized controlled pilot trial of naloxone on release to prevent post prison opioid overdose deaths
    Addiction, 2017
    Co-Authors: Mahesh K B Parmar, John Strang, Louise Choo, Angela M Meade, Sheila M Bird
    Abstract:

    The pilot N-ALIVE Trial was grant-funded by the Medical Research Council (MC_G0800012) and coordinated by the MRC Clinical Trials Unit at University College London, which core-funds M.K.B.P., L.C. and A.M.M. S.M.B. was funded by Medical Research Council programme number MC_U105260794. J.S. is core-funded by his university, King’s College London. The MRC’s funding board had no role in data analysis, data interpretation, or writing of the report.

F Shepherd - One of the best experts on this subject based on the ideXlab platform.

  • the strength of female sex as a prognostic factor in small cell lung cancer a pooled analysis of chemotherapy Trials from the manchester lung group and medical research council Clinical Trials Unit
    Annals of Oncology, 2010
    Co-Authors: Paul Wheatleyprice, R J Stephens, L Ashcroft, M Nankivell, Shane White, Paul Lorigan, Nick Thatcher, Fiona H Blackhall, F Shepherd
    Abstract:

    BACKGROUND: Previous studies reported that women survive longer than men, but experience greater toxicity, when treated for small-cell lung cancer (SCLC). METHODS: Individual patient data from six randomized phase II/III chemotherapy Trials, from the Manchester Lung Group and UK Medical Research Council, were pooled for analysis. End points included overall survival, response rate, toxicity, dose intensity (DI) and transfusion rates. RESULTS: Of 1707 patients analyzed, 44% were women. At baseline, women had poorer performance status (PS) (57% versus 67% Eastern Cooperative Oncology Group PS 0-1/Karnofsky PS 80-100, P = 0.0004) and more were of normal weight or underweight (57% versus 48%, P = 0.003), but fewer were anemic (25% versus 62%, P 1700 patients in randomized SCLC chemotherapy Trials confirm that women survive modestly longer than men but may experience greater toxicity.

Matthew R. Sydes - One of the best experts on this subject based on the ideXlab platform.

  • benefit of prostate radiotherapy for patients with lymph node only or 4 bone metastasis and no visceral metastases exploratory analyses of metastatic site and number in the stampede m1 rt comparison
    Annals of Oncology, 2019
    Co-Authors: S A Ali, Malcolm David Mason, Chris Parker, A Hoyle, N D James, Christopher D Brawley, G Attard, Hassan Douis, M K B Parmar, Matthew R. Sydes
    Abstract:

    Abstract Background Prostate radiotherapy (PRT) with androgen deprivation therapy (ADT) is now recommended as a first line option for de-novo low burden metastatic prostate cancer. In the STAMPEDE “M1|RT comparison” metastatic burden was a determinant of benefit, based on pre-specified prognostic criteria. We have now performed exploratory analyses of metastases as defined by site and number to improve prediction of treatment benefit from PRT. Methods Patients (pts) randomized to the ADT (± docetaxel) vs PRT + ADT (± docetaxel) were studied. Metastatic site, distribution and number were evaluated based on conventional imaging and used to explore treatment effects to refine the metastatic burden definition. Results focused on the trial’s key outcome measures: overall (OS) & failure-free survival (FFS), analysed using standard survival analysis methods. HR  Results Following exclusions (imaging unavailable for central review, n = 122), 1939 pts randomized in “M1|RT comparison” were included. Of these, 181 pts had only lymph node (LN) mets, 1587 had bone (±LN) mets and 171 had other visceral mets (±bone/LN). Baseline characteristics such as age (median 68 years), PSA (median 98 ng/ml) were balanced between the arms. In LN only pts, PRT improved OS (HR = 0.62, 95%CI 0.35-1.09) & FFS (HR = 0.64, 95%CI 0.43-0.96). In bone (±LN) pts with 0.1) for baseline factors such as age, N stage, Gleason score, RT schedule or docetaxel use. Conclusions Prostate RT + ADT (± docetaxel) improved OS & FFS in pts with only LN or  Clinical trial identification NCT00268476. Legal entity responsible for the study Medical Research Council-Clinical Trials Unit and University of Manchester. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

  • testing many treatments within a single protocol over 10 years at mrc Clinical Trials Unit at ucl multi arm multi stage platform umbrella and basket protocols
    Clinical Trials, 2017
    Co-Authors: Mahesh K B Parmar, Matthew R. Sydes, Melissa R. Spears, Ruth E Langley, Fay H Cafferty, Babak Choodarioskooei, Louise Brown, Patrick P J Phillips, Sam Rowley, Richard Kaplan
    Abstract:

    There is real need to change how we do some of our Clinical Trials, as currently the testing and development process is too slow, too costly and too failure-prone often we find that a new treatment is no better than the current standard. Much of the focus on the development and testing pathway has been in improving the design of phase I and II Trials. In this article, we present examples of new methods for improving the design of phase III Trials (and the necessary lead up to them) as they are the most time-consuming and expensive part of the pathway. Key to all these methods is the aim to test many treatments and/or pose many therapeutic questions within one protocol.

  • The value of evidence synthesis in randomised controlled trial (RCT) design, conduct and analysis: MRC Clinical Trials Unit (CTU) at UCL experience
    Trials, 2015
    Co-Authors: Jayne F Tierney, Claire L Vale, Matthew R. Sydes, Ruth E Langley, Sarah Burdett, Larysa Rydzewska, Richard Kaplan, Mahesh K B Parmar
    Abstract:

    Background Systematic reviews of RCTs are recognised as the optimal way to resolve or confirm uncertainty about the effects of interventions. They can provide the rationale for the design of a new trial, inform the conduct of an ongoing trial, and help place trial results in the context of those from related Trials. However, empirical evidence suggests that few Trials use systematic reviews in these ways.

  • 19LBA Docetaxel (Doc) +/− zoledronic acid (ZA) for hormone-naive prostate cancer: First overall survival results from STAMPEDE & treatment effects within subgroups (NCT00268476)
    European Journal of Cancer, 2015
    Co-Authors: Nicholas D. James, Matthew R. Sydes, Malcolm David Mason, N.w. Clarke, David P. Dearnaley, Melissa R. Spears, Robin Millman, Chris Parker, A.w.s. Ritchie, J.m. Russell
    Abstract:

    N.D. James, M.R. Sydes, M.D. Mason, N.W. Clarke, D.P. Dearnaley, M.R. Spears, R. Millman, C.C. Parker, A.W.S. Ritchie, J.M. Russell, J. Staffurth, R.J. Jones, R. Cathomas, A. Robinson, S. Chowdhury, D. Tsang, S. Brock, O. Parikh, J.D. Graham, M.K.B. Parmar. Warwick University, Clinical Trials Unit, Coventry, United Kingdom; Medical Research Council Clinical Trials Unit at UCL, Institute for Clinical Trials and Methodology, London, United Kingdom; Cardiff University, School of Medicine, Cardiff, United Kingdom; The Christie NHS Foundation Trust, Department of Urology, Manchester, United Kingdom; The Institute of Cancer Research and Royal Marsden Hospital NHS Trust, Academic Unit of Radiotherapy, London, United Kingdom; Medical Research Council Clinical Trials Unit at UCL, Patient Representative, NA, United Kingdom; The Royal Marsden Hospital, Department of Radiotherapy, London, United Kingdom; Beatson West of Scotland Cancer Centre, Institute of Cancer Sciences, Glasgow, United Kingdom; Cardiff University and Velindre NHS Trust, School of Medicine, Cardiff, United Kingdom; Kantonsspital Graubunden, Department of Oncology, Chur, Switzerland; Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, United Kingdom; Guy’s Hospital, Department of Medical Oncology, London, United Kingdom; Southend & Basildon Hospitals, Department of Oncology, Southend, United Kingdom; Poole Hospital NHS Foundation Trust and Royal Bournemouth Hospital NHS Foundation Trust, Department of Oncology, Poole, United Kingdom; East Lancashire Hospitals NHS Trust, Department of Oncology, Blackburn, United Kingdom; Musgrove Park Hospital, Oncology and Haematology Clinical Trials Unit, Taunton, United Kingdom

Noreen Hopewell-kelly - One of the best experts on this subject based on the ideXlab platform.