Mahesh Parmar

• DPhi
• Managing Director at University College London

Participants in clinical trials should be pro-actively offered the results of trials in which they have participated. This should be done in a way that is accessible and understandable for all participants. People who have taken part in research have a right to know the results of the studies in which they have taken part and should be given the op...

The impact on immunogenicity and efficacy of SARS-CoV-2 vaccination in people with prior COVID-19 could differ depending on timing of vaccination and number of doses. The VATICO study randomized 66 hospitalized recovered COVID-19 individuals to receive either immediate or deferred vaccination, with one or two doses of mRNA SARS-CoV-2 vaccines. We m...

This article consists of a citation of a published article describing research funded by the Health Technology Assessment programme under project number 16/46/01, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1002/uog.21894 Objective Estrogen is...

This article consists of a citation of a published article describing research funded by the Health Technology Assessment programme under project number 16/46/01, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.3390/diagnostics10020089 Background T...

This article consists of a citation of a published article describing research funded by the Health Technology Assessment programme under project number 16/46/01, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1111/1471-0528.16943 Objective To inv...

This article consists of a citation of a published article describing research funded by the Health Technology Assessment programme under project number 16/46/01, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1016/S0140-6736(21)00731-5 Summary B...

This article consists of a citation of a published article describing research funded by the Health Technology Assessment programme under project number 16/46/01, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1186/s13063-020-04968-x Background Th...

This article consists of a citation of a published article describing research funded by the Health Technology Assessment programme under project number 16/46/01, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1186/s13063-021-05125-8 Background Du...

This article consists of a citation of a published article describing research funded by the Health Technology Assessment programme under project number 16/46/01, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.3390/cancers13040858 Randomised contro...

This article consists of a citation of a published article describing research funded by the Health Technology Assessment programme under project number 16/46/01, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1016/j.ygyno.2023.11.005 Objective UK...

This article consists of a citation of a published article describing research funded by the Health Technology Assessment programme under project number 16/46/01, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1016/j.ygyno.2020.05.002 Objective Th...

This randomized clinical trial explores whether hormone intensification at start of androgen deprivation therapy alters selection of androgen receptor ( AR ) gene alterations within the gene body and/or enhancer region.

234 Background: The HSD3B1 gene encodes for the 3βHSD1 enzyme which regulates the rate-limiting step in potent androgen synthesis from non-gonadal precursors. The missense-encoding adrenal-permissive form of HSD3B1 generates a hyperactive 3βHSD1 enzyme compared to the adrenal-restrictive form. We aimed to test associations with OS for HSD3B1 genoty...

20 Background: Clinical features of people with mHSPC may affect their outcomes from the addition of ARPIs to androgen deprivation therapy (ADT). The STOPCAP Collaboration is seeking IPD to reliably investigate potential ARPI effect modifiers and determine who benefits more from an ARPI vs docetaxel plus ADT doublet. Methods: Full methods are in re...

21 Background: Recent phase III data (n=1360) has shown that starting ADT with tE2 patches is non-inferior in terms of metastasis-free survival (with similar overall survival) to luteinising hormone releasing hormone analogues (LHRHa) for locally advanced (M0) prostate cancer. For both M0 and M1 patients, tE2 has advantages in terms of reported qua...

The window period for detection of early stage disease (pre clinical detectable phase) is only ~12months. The invivo tumour doubling time is ~2.9 months. This has important implications for diagnostic pathways and developing screening strategies.

Conventional trial designs are resource and time-intensive. To accelerate the process of testing new interventions, we now have several novel research trial designs. This article focuses on master protocol trials, which allow several therapies to be tested within a single larger trial.

Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic...

Clinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period. In this paper we describe how we modified the design of th...

Introduction/aims: Healthcare systems data (also known as real-world or routinely collected health data) could transform the conduct of clinical trials. Demonstrating integrity and provenance of these data is critical for clinical trials, to enable their use where appropriate and avoid duplication using scarce trial resources. Building on previous...

Background and objective The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no (“None”), 6-months (“Short”), or 24-mo (“Long”) ADT to study efficacy in the long term. Methods Participants with prostate cancer were indicated for postoperative RT and agreed...

Background Multi-arm multi-stage (MAMS) randomised trial designs have been proposed to evaluate multiple research questions in the confirmatory setting. In designs with several interventions, such as the 8-arm 3-stage ROSSINI-2 trial for preventing surgical wound infection, there are likely to be strict limits on the number of individuals that can...

Background Multimorbidity poses a global challenge to healthcare delivery. This study aimed to describe the prevalence of multimorbidity, common disease combinations and outcomes in a contemporary cohort of patients undergoing major abdominal surgery. Methods This was a pre-planned analysis of a prospective, multicentre, international study investi...

The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Rev...

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised contr...

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICAL...

Background The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. Patients and methods RADICALS-RT was a randomised controlled trial enrolling patient...

Abstract Cardiovascular complications after major surgery are associated with increases in morbidity and mortality. There is confusion over definitions of cardiac injury or complications, and variability in the assessment and management of patients. This international prospective cohort study aimed to define the incidence and timing of these compl...

Background It is unclear how to disseminate the results of randomised controlled trials effectively to health professionals and policymakers to improve treatment, care or prevention through changing policy and practice. This systematic review examined the effectiveness of different methods of dissemination of clinical research results to profession...

Introduction Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%–40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intellige...

Objective UKCTOCS provides an opportunity to explore symptoms in preclinical invasive epithelial ovarian cancer (iEOC). We report on symptoms in women with pre-clinical (screen-detected) cancers (PC) compared to clinically diagnosed (CD) cancers. Methods In UKCTOCS, 202638 postmenopausal women, aged 50–74 were randomly allocated (April 17, 2001-Se...

Background Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. Methods Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placeb...

Aims Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity...

Background A 2×2 factorial design evaluates two interventions (A versus control and B versus control) by randomising to control, A-only, B-only or both A and B together. Extended factorial designs are also possible (e.g. 3×3 or 2×2×2). Factorial designs often require fewer resources and participants than alternative randomised controlled trials, bu...

Clinical Trials in Cancer provides concise, accessible and practical information on the practicalities of planning, designing, conducting, analysing, reporting, and interpreting phase III clinical trials predominantly, but also single-arm and randomized phase II trials. The book shows clearly how recent developments and current thinking can be impl...

Introduction/Background First-line phase III trials in stage III/IV Epithelial Ovarian Cancer (EOC) have shown improved survival both with addition of bevacizumab (BEV) to three-weekly (q3w) carboplatin (C)-paclitaxel (T) and integration of weekly dose-dense paclitaxel (ddwT) with carboplatin compared to q3wCT alone. ICON8B, a 3-arm trial, compared...

We introduce two commands, nstagebin and nstagebinopt, that can be used to facilitate the design of multiarm multistage (MAMS) trials with binary outcomes. MAMS designs are a class of efficient and adaptive randomized clinical trials that have successfully been used in many disease areas, including cancer, tuberculosis, maternal health, COVID-19, a...

Background: In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy. Methods: UKCT...

Randomised controlled trials are challenging to deliver. There is a constant need to review and refine recruitment and implementation strategies if they are to be completed on time and within budget. We present the strategies adopted in the United Kingdom Collaborative Trial of Ovarian Cancer Screening, one of the largest individually randomised co...

Background: Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecif...

Aims: The forthcoming STAMPEDE2 trial has three comparisons in metastatic hormone-sensitive prostate cancer. We aim to determine clinical practices among STAMPEDE trial investigators for access to imaging and therapeutic choices and explore their interest in participation in STAMPEDE2. Materials and methods: The survey was developed and distribu...

Atopic eczema is common and profoundly impacts on the quality of life, and psychological and social function. More severe disease often requires systemic (standard or targeted) immune-modifying therapy; however, drug response and tolerability vary in practice. As the molecular effects of the drugs used have not been characterized in detail, the cau...

Background: The population-level summary measure is a key component of the estimand for clinical trials with time-to-event outcomes. This is particularly the case for non-inferiority trials, because different summary measures imply different null hypotheses. Most trials are designed using the hazard ratio as summary measure, but recent studies sug...

5073 Background: Prior analyses have shown that men who present with high volume (HV) disease and de novo metastases have shorter OS compared with other mHSPC subgroups. The objective of this analysis was to determine the prognostic relationship between a-priori defined 4-prognostic groups and OS in men with mHSPC and in a subset of trials in patie...

e15069 Background: The MCED Consortium is a group of volunteers, advisors, and companies from the US and the UK spanning a wide range of expertise in biomarker evaluation and implementation, with a special focus on clinical practice, health equity, and communication. The development of Multi Cancer Early Detection (MCED) markers may herald a new ap...

TPS9145 Background: Pharmacological and clinical data suggest standard regimens for anti-PD1 agents nivo and pembro result in overtreatment. These agents have high target affinity, saturate PD1 at very low concentrations and maintain receptor occupancy for up to 30 wks following discontinuation. Clinical studies suggest no dose-response relationshi...

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation ther...

Increasing evidence suggests that some immunotherapy dosing regimens for patients with advanced cancer could result in overtreatment. Given the high costs of these agents, and important implications for quality of life and toxicity, new approaches are needed to identify and reduce unnecessary treatment. Conventional two-arm non-inferiority designs...

Unlabelled: Emerging data indicate comparable disease control and toxicity of postoperative normo-fractionation and moderate hypofractionation radiotherapy (RT) in prostate cancer. In RADICALS-RT, patients were planned for treatment with either 66Gy in 33 fractions over 6.5 weeks or 52.5Gy in 20 fractions over 4 weeks. In this non-randomized, expl...

Background Ovarian and tubal cancers are lethal gynaecological cancers, with over 50% of the patients diagnosed at advanced stage. Trial design Randomised controlled trial involving 27 primary care trusts adjacent to 13 trial centres based at NHS Trusts in England, Wales and Northern Ireland. Methods Participants Postmenopausal average-risk wome...

Background. The DURATIONS design has been recently proposed as a practical alternative to a standard two-arm non-inferiority design when the goal is to optimise some continuous aspect of treatment administration, e.g. duration or frequency, preserving efficacy but improving on secondary outcomes such as safety, costs or convenience. The main featur...

We describe a new command, artcat, that calculates sample size or power for a randomized controlled trial or similar experiment with an ordered categorical outcome, where analysis is by the proportional-odds model. artcat implements the method of Whitehead (1993, Statistics in Medicine 12: 2257–2271). We also propose and implement a new method that...

We describe the command artbin, which offers various new facilities for the calculation of sample size for binary outcome variables that are not otherwise available in Stata. While artbin has been available since 2004, it has not been previously described in the Stata Journal. artbin has been recently updated to include new options for different st...

Introduction For patients with advanced epithelial ovarian cancer, complete surgical cytoreduction remains the strongest predictor of outcome. However, identifying patients who are likely to benefit from such surgery remains elusive and to date few surgical outcome prediction tools have been validated. Here we attempted to externally validate a pro...

Background: Routinely-collected healthcare systems data (HSD) are proposed to improve the efficiency of clinical trials. A comparison was undertaken between cardiovascular (CVS) data from a clinical trial database with two HSD resources. Methods: Protocol-defined and clinically reviewed CVS events (heart failure (HF), acute coronary syndrome (AC...

An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to Phase 3 for those candidates passing an interim signal of efficacy. Replicating this comp...

Metastatic and high-risk localized prostate cancer respond to hormone therapy but outcomes vary. Following a pre-specified statistical plan, we used Cox models adjusted for clinical variables to test associations with survival of multi-gene expression-based classifiers from 781 patients randomized to androgen deprivation with or without abiraterone...

Background: Multi-arm multi-stage trials are an efficient, adaptive approach for testing many treatments simultaneously within one protocol. In settings where numbers of patients available to be entered into trials and resources might be limited, such as primary postpartum haemorrhage, it may be necessary to select a pre-specified subset of arms a...

Background MND-SMART is a platform, multi-arm, multi-stage, multi-centre, randomised controlled trial recruiting people with motor neuron disease. Initially, the treatments memantine and trazodone will each be compared against placebo, but other investigational treatments will be introduced into the trial later. The co-primary outcomes are the Amyo...

Background: The Cytosponge is a cell-collection device, which, coupled with a test for trefoil factor 3 (TFF3), can be used to diagnose Barrett's oesophagus, a precursor condition to oesophageal adenocarcinoma. BEST3, a large pragmatic, randomised, controlled trial, investigated whether offering the Cytosponge-TFF3 test would increase detection of...

Background Late-phase platform protocols (including basket, umbrella, multi-arm multi-stage (MAMS), and master protocols) are generally agreed to be more efficient than traditional two-arm clinical trial designs but are not extensively used. We have gathered the experience of running a number of successful platform protocols together to present som...

Background: Genomic copy number alterations commonly occur in prostate cancer and are one measure of genomic instability. The clinical implication of copy number change in advanced prostate cancer, which defines a wide spectrum of disease from high-risk localised to metastatic, is unknown. Methods: We performed copy number profiling on 688 tumou...