The Pragmatic Clinical Trials Unit (PCTU) leads and supports clinical trials in which the primary question of interest relates to intervention effectiveness: whether an intervention works under real-life conditions.
It also leads and supports pilot studies for these trials. Currently, the unit focuses on trials of complex interventions, and on trials designed to understand processes explaining effectiveness, but also supports a small number of other pragmatic trials. In addition, the unit leads methodological research relevant to its focus.
The aim of the unit is to lead, support and encourage high quality pragmatic trials and pilot studies particularly where they fit with the research strategies of the two centres with which the unit is linked, or with the methodological interests of the unit.
The PCTU is based in the Centre for Primary Care and Public Health and linked to the Centre for Psychiatry. We have been conducting pragmatic clinical trials since the mid 1990s. We have considerable experience and expertise in primary care, community-based and mental health trials, and particularly cluster randomised trials and trials of complex interventions and behaviour change.
We are a UK Clinical Research Collaboration (UKCRC) registered clinical trials unit.
This unit receives National Institute for Health Research CTU Support Funding. This funding has been awarded to support the unit in developing and supporting NIHR trials.
What does a clinical trials unit do?
The UKCRC defines a clinical trials unit as a unit with overall responsibility for the design, recruitment, data management, publicity and analysis of multi-centred randomised controlled trials or other well-designed studies, working in any disease/topic area. There are more details on their website.
Some trials units are generic, covering all types of trial and disease areas. Other trials units, like the PCTU, have a more specific focus.
The PCTU is currently involved in these projects, which are at varying stages of completion and led by a variety of investigators. For further information please click on the title.
DAPPA - How accurate is spot urinary protein:creatinine ratio (SPCr) and spot albumin:creatinine ratio (SACr) compared to 24-hour protein estimation to assess women with hypertensive disease in pregnancy (HDP) after 24 weeks gestation.
EMPIRE - Antiepileptic drug (AED) management in Pregnancy: An evaluation of effectiveness, cost effectiveness and acceptability of dose adjustment strategies
ENRICH - Enhanced discharge from inpatient to community mental health care (ENRICH): a programme of applied research to manualise, pilot and trial a Peer Worker intervention
EPOCH - Enhanced Peri-Operative Care for High-risk patients (EPOCH) Trial. A stepped wedge randomised cluster trial of an intervention to improve quality of care for patients undergoing emergency laparotomy
ESTEEM: Effect of simple, targeted diet in pregnant women with metabolic risk factors on pre-eclampsia: A randomised trial
FIAT - Financial incentives to improve adherence to anti-psychotic maintenance medication in non-adherent patients – a cluster randomised controlled trial
HABSelect - Hyaluronic Acid Binding for Sperm sELECTion
MEDAL- Can magnetic resonance imaging (MRI) scan replace or triage the use of laparoscopy in establishing a diagnosis among women presenting in secondary care with chronic pelvic pain (CPP)?
NESS - Effectiveness and Cost-Effectiveness of Body Psychotherapy in the Treatment of Negative Symptoms of Schizophrenia – A multi-centre randomised controlled trial
PACE-UP - Randomised controlled trial of a pedometer-based walking intervention with and without practice nurse support in primary care patients aged 45-74 years
PIMS - A multicentre interventional comparative randomised controlled clinical trial comparing face-down positioning, with an inactive face-forward position on the outcome of surgery for large macular holesPositioning in Macular hole Surgery (Positioning in Macular hole Surgery)
SALVO - A randomised controlled trial of intra-operative cell salvage during caesarean section in women at risk of haemorrhage
SWAP - A peer-support weight management programme to supplement brief advice in general practice for obese adults from deprived communities
CapaCiTY - Chronic Constipation Treatment pathwaY
EPOS - Effective patient-clinician interaction to improve treatment outcomes for patients with psychosis
HepFree – Chronic viral hepatitis in ethnic minorities. Strategies to prevent the predicted increase in mortality
QuEST – Quality and Effectiveness of Supported Tenancies for people with mental health problems
STOP - Optimising pharmacist-based treatment for smoking cessation
VOLUME - Volunteering in Mental Health Care for People with Psychosis
iWIP - Effects of weight management interventions on maternal and fetal outcomes in pregnancy: Individual patient data (IPD) meta analysis of randomised trials and model based economic evaluation
PREP - Development and validation of a Prediction model for Risk of complications in Early onset Pre-eclampsia
START - Systematic Techniques for Assessing Recruitment to Trials: a programme to test recruitment interventions
Completed Projects and Publications
Below is a list of projects that PCTU staff have been involved with in the past. These projects are now completed and resulting publications as well as further information on the trial will be available from links below.
AdjuVIT - Does vitamin D enhance response to treatment in smear positive pulmonary tuberculosis? A double-blind randomised placebo-controlled trial
BELLA - Development, pilot and feasibility study for a chronic obstructive pulmonary disease (COPD) specific version of the Expert Patients Programme (EPP)
Body Psychotherapy - Effectiveness and processes of body psychotherapy in Chronic schizophrenia
Calcitriol trial - Does 1,25-dihydroxyvitamin D3 (calcitriol) enhance corticosteroid activity in steroid-refractory asthma?
ComQuol – A pilot trial to assess the effect of a structured Communication approach on QUality Of Life in secure mental health settings
CONFIDeNT - Control of faecal incontinence using distal neuromodulation
DIALECT - Dialectical-behaviour therapy for people with borderline personality disorders and self harm - a pragmatic pilot trial
The Diabetes Manual - Effectiveness of patient self-managed structured education for type 2 diabetes: a cluster randomised-controlled trial
IRIS - Primary care Identification and Referral to Improve Safety of women experiencing partner violence: a randomised controlled trial
MEDEA - Does the chronic disease self-management programme (expert patient programme) improve metabolic control of diabetes? A randomised controlled trial
Music Therapy - Group music therapy for patients with treatment resistant posttraumatic stress disorder – a pilot randomised controlled trial
OEDIPUS - Can education for South Asians with asthma and their clinicians reduce unscheduled care? A cluster randomised trial and qualitative evaluation
OPERA - Older people's exercise intervention in residential nursing accommodation
RHIVA 2 - Effectiveness of HIV screening in primary care: a cluster RCT and economic analysis
SNS vs PTNS - A randomised mixed methods pilot (phase II exploratory trial) of sacral and percutaneous tibial nerve stimulation for faecal incontinence
WAIT - Parent-determined oral montelukast therapy for preschool wheeze with stratification for arachidonate-5-lipoxygenase (ALOX5) promoter genotype
COPERS - COping with Persistent Pain, Effectiveness Research into Self-management
OViD - Effectiveness of vitamin D supplementation to prevent acute respiratory illness and reduce health care use. The OViD programme encompasses the following trials:
ASAP - Is poor educational attainment in white and Bangladeshi children related to asthma? A study linking health, education and social care datasets
Developing and piloting a new intervention to improve psychiatrist-patient communication about psychosis
GEM Study (Guided E-learning for Managers ) - Pilot study of a randomised trial of a guided e-learning health promotion intervention for managers based on management standards for the improvement of employee wellbeing and reduction of sickness absence
HiLo - High blood pressure control and lipid Lowering in patients at high cardiovascular risk: a cluster-randomised factorial comparison of educational and protocol
LEZ - Impact of the London Low Emission Zone on Children's Respiratory Health
LPE /Homeless study - Discharge planning for the homeless, examining The London Pathway. Does a GP led discharge team reduce the in-patient burden and improve quality of care?
TOPAS - Measuring and understanding the meaning of chronic widespread pain amongst Bangladeshis in Tower Hamlets, East London
We undertake methodological research emerging directly out of discussions and deliberations around specific trials; this is an important part of the way in which we ensure that we stay at the forefront of the science and execution of pragmatic trials. Important and interesting questions can often be answered in a short time frame with no need for external funding. Senior academic staff also have their own longer term research interests. In particular we have long term interests in cluster randomised trials, pilot and feasibility studies, innovative trial design, and best practice in the design, analysis and reporting of trials. We try to keep a balance between following interesting new avenues and focusing on specific areas.
Internal and external validity of cluster randomised trials
Definitions of the Intra-cluster correlation coefficient
Issues in cluster randomised trials in dentistry: a systematic review
A Practical Guide to Cluster Randomised Trials
Issues in cluster randomised trials in nursing homes: a systematic review (part of NIHR NCCRCD research methods training fellowship October 2009- Sept 2013)
Are missing data adequately handled in cluster randomised trials? A systematic review
The Ottawa statement on the ethical design and conduct of cluster randomised trials
Review of published cluster-crossover trials
Developing new Cochrane Risk of Bias Tool (Cluster randomised trials sub-group)
Development and design of pragmatic and cluster randomised trials (NIHR methods fellowship)
Mediation analysis in cluster randomised trials
Analysis of stepped wedge trials
Interim sample size calculations for cluster randomised trials
Cluster effects in patients and clinicians rating the same outcome
Cluster effects of clinician ratings on patient outcomes
Cascade diagrams: a new graphical method for depicting complex interventions in randomised trials
Covariates in cluster randomised trials (PhD thesis)
Analysis of cluster-randomised cross-over trials with binary outcomes (MSc project)
Developing simple appropriate sample size formulae for ordinal, count or time to event outcomes in cluster randomised trials (PhD thesis)
Review of published cluster randomised trials with small numbers of clusters
Analysis of cluster randomised trials with a baseline assessment of outcome
Secondary analysis of longitudinal, clustered data-sets to estimate parameters for sample size calculations for longitudinal, cluster randomised trials
External validity of a pragmatic trial of self-monitoring and self-management (NIHR Research Methods Fellowship)
Applying PRECIS-2 to primary care trials (Research Methods Fellowship)
Understanding the effectiveness of complex behavioural interventions
CONSORT reporting guidance for pilot studies
Uncertainty in estimates of ICCs from pilot studies
Comparing diagnostic tests: trials in people with discordant test results
Software for versatile sample size calculation
The dog-leg, and other alternatives to parallel groups designs for pragmatic clinical trials
Individually randomised stepped wedge designs for trials with a waiting-list control
A re-randomisation design to increase patient recruitment in clinical trials
Dichotomising continuous data while retaining statistical power using a distributional approach
Covariate adjustment in randomised trials
Analysis of randomised trials with partially missing outcome data
Improved per-protocol analyses in non-inferiority trials
Clustering in individually randomised trials
Bias arising from factorial designs, and why an initial test for interaction is incorrect
What makes a good sensitivity analysis in a randomised trial?
Withdrawal of inhaled corticosteroids in individuals with COPD – a systematic review and comment on trial methodology
Reporting outcomes of back pain trials
Adjustment for continuous covariates in randomised controlled trials
[I’m not sure if this is the same thing as the existing "covariate adjustment in randomised trials"]
Analysis of multicentre trials with small numbers of events or patients in each cluster
Blinded outcome assessment in open label trials, and reducing bias when blinded outcome assessment is not feasible
Pinnock H, Epiphaniou E, Sheikh A, Griffiths C, Eldridge S, Craig P, Taylor SJC. Developing standards for reporting implementation studies of complex interventions (StaRI): A systematic review and e-Delphi. Implementation Sci 2015;10(1):42.
Rutterford C, Taljaard M, Dixon S, Copas A, Eldridge S. Reporting and methodological quality of sample size calculations in cluster randomized trials could be improved: A review. J Clin Epidemiol 2015;68(6):716-723.
Wright N, Ivers N, Eldridge S, Taljaard M, Bremner S. A review of the use of covariates in cluster randomized trials uncovers marked discrepancies between guidance and practice. J Clin Epidemiol 2015;68(6):603-609.
Arnup SJ, Forbes AB, Kahan BC, Morgan KE, McDonald S, McKenzie JE. The use of the cluster randomized crossover design in clinical trials: protocol for a systematic review. Systematic Reviews 2014, 3:86.
Díaz-Ordaz K, Kenward MG, Cohen A, Coleman CL, Eldridge S. Are missing data adequately handled in cluster randomised trials? A systematic review and guidelines. Clin Trials published online 5 June 2014 DOI: 10.1177/1740774514537136.
Kahan BC, Cro S, Doré CJ, Bratton DJ, Rehal S, Maskell NA, Rahman N, Jairath V. Reducing bias in open-label trials where blinded outcome assessment is not feasible: strategies from two randomised trials. Trials 2014;15(1):456.
Rick J, Graffy J, Knapp P, Small N, Collier DJ, Eldridge S, Kennedy A, Salisbury C, Treweek S, Torgerson D, Wallace P, Madurasinghe V, Hughes-Morley A, Bower P. Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials. Trials. 2014;15(1):407.
Weijer C, Taljaard M, Grimshaw JM, Edwards SJL, Eccles MP & Group tOEoCRTC. The Ottawa statement on the ethical design and conduct of cluster randomized trials: a short report. Research Ethics 2014;10(2):77-85.
Diaz-Ordaz K, Froud R, Sheehan B & Eldridge S. A systematic review of cluster randomised trials in residential facilities for older people suggests how to improve quality. BMC Med Res Methodol 2013;13:127.
Diaz-Ordaz K, Slowther AM, Potter R & Eldridge S. Consent processes in cluster-randomised trials in residential facilities for older adults: a systematic review of reporting practices and proposed guidelines. BMJ Open 2013;3(7).
Taljaard M, Weijer C, Grimshaw JM, Eccles MP & Group tOEoCRTC. The Ottawa Statement on the ethical design and conduct of cluster randomised trials: precis for researchers and research ethics committees. BMJ 2013;346:f2838.
Choudhury Y, Hussain I, Parsons S, Rahman A, Eldridge S & Underwood M. Methodological challenges and approaches to improving response rates in population surveys in areas of extreme deprivation. Prim Health Care Res Dev 2012;13(3):211-218.
Froud R, Eldridge S, Diaz Ordaz K, Marinho VC & Donner A. Quality of cluster randomized controlled trials in oral health: a systematic review of reports published between 2005 and 2009. Community Dent Oral Epidemiol 2012;40 Suppl 1:3-14.
Weijer C, Grimshaw JM, Eccles MP, McRae AD, White A, Brehaut JC, Taljaard M & Group tOEoCRTC. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials. PLoS Med 2012;9(11):e1001346.
Froud R, Eldridge S, Kovacs F, Breen A, Bolton J, Dunn K, Fritz J, Keller A, Kent P, Lauridsen HH, Ostelo R, Pincus T, van Tulder M, Vogel S & Underwood M. Reporting outcomes of back pain trials: a modified Delphi study. Eur J Pain 2011;15(10):1068-1074.
Lancaster GA, Campbell MJ, Eldridge S, Farrin A, Marchant M, Muller S, Perera R, Peters TJ, Prevost AT & Rait G. Trials in primary care: statistical issues in the design, conduct and evaluation of complex interventions. Stat Methods Med Res 2010;19(4):349-377.
Director: Sandra Eldridge (statistician)
Deputy Director and clinical lead, mental health: Stefan Priebe (psychiatrist)
Senior academic staff
Clinical lead, chronic conditions & primary care: Stephanie Taylor (GP)
Clinic lead, surgical research: Charles Knowles (colorectal surgeon)
Clinical lead, translational research & primary care: Chris Griffiths (GP)
Clinical lead, women’s health: Khalid Khan (obstetrician)
Chair in health economics: Anita Patel
Reader in medical statistics: Sally Kerry
Senior lecturer in medical statistics: Richard Hooper
Senior lecturer in medical statistics: Gian Luca Di Tanna
Senior lecturer in clinical trials: Ayesha de Costa
Senior managerial and administrative staff
Head of Operations: Tahera Hussain
Quality assurance manager: Anitha Manivannan
Clinical trials information systems (CTIS) manager: Arouna Woukeu
PCTU administrator: Charlotte Ayton-George
Senior trials managers
Generic: Ann Thomson
Translational health: Bev MacLaughlin
Surgical Unit: Tash Stevens
Women’s health: Julie Dodds
The unit also has statisticians, health economists, database programmers, monitors and administrators who each work across a number of projects, and trial managers, trial coordinators, data assistants, research nurses who usually focus on individual projects.
Staff role definitions
We want to ensure researchers get the best possible support from the Pragmatic Clinical Trials Unit and know who is responsible for which tasks within the unit. Different clinical trials units operate differently so this guide applies specifically to the Pragmatic Clinical Trials Unit.
Please see below outlines of some of the roles individuals can play within a trial. You may wish to refer to this guide in combination with the support services available when requesting PCTU support. Staff listed below are employed by the PCTU. Funding for their roles is incorporated in research grant applications, and for successful grants this funding is then paid by the organisation that receives the grant direct to the PCTU to pay these staff.
PCTU data managers: Tom Power, Mike Waring
We offer database design appropriate to the individual needs of each project we support. The data manager will develop appropriate data management strategies for trials and advise on their implementation. They will advise on current regulatory framework regarding data protection and data management procedures in compliance with data protection act and other regulations.
The data manager will advise on suitable database for individual study and set up databases in liaison with chief investigators, statisticians and health economists working on trials. Each database will have integrated data validation checks and full audit trails. Clinical and patient identifiable data are kept on physically separate databases. The data manager will advise on and set up data transfer systems and encryption systems so that all patient identifiable data is encrypted. The data manager will also advise on storage, back-up and archiving of data to ensure databases are regularly backed up to ensure data are safeguarded from accidental loss. In addition to this data management covers the following tasks:Advise on case report form (CRF) design
- Agree with chief investigator time line for database set up and database lock
- With chief investigator, draw up trial data management SOPs.
PCTU health economist: Natalia Hounsome
In some clinical trials, it can be important to compare how much different treatments cost, as well as how well they work. This can be particularly important when two (or more) treatments are equally effective, but differ considerably in their costs. An economic evaluation as offered by our health economist will ensure that all costs (treatment, care and recovery, as well as the costs of prevention, research and training of healthcare personnel) have been considered when the trial results are presented.
The health economist will:
- Develop plans for economic analyses and advise on appropriate data collection
- Collaborate with statisticians and data managers working on trials to ensure appropriate data management systems
- Carry out economic analyses for trials including modelling
- Input into report and publication papers.
Quality Assurance Officer
PCTU QA managers: Anitha Manivannan
The quality assurance officer will train trial staff in PCTU and Joint Research Office's Standard Operating Procedures (SOPs) as relevant to their work, liaise with chief investigators regarding set up trial master files and carry out audits of the trial master file for ongoing quality assurance. They will also ensure compliance with GCP regulations and advise on staff GCP requirements, clinical trial regulatory requirements, adverse event reporting and on PCTU support available.
PCTU Head of Operations
PCTU Head of Operations: Tahera Hussain
The PCTU Head of Operations will act on behalf of the unit director and negotiate with chief investigators over PCTU involvement in trial, agreeing costs and timing. The Head of Operations will liaise with the Joint Research Office over costings for PCTU staff and with grant holding organisation regarding transfer of funds for PCTU support. They manage the PCTU budget and also liaise with R&D departments to ensure necessary contracts are in place.
PCTU administrator: currently vacant
The administrator acts as first point of contact for researchers wishing to collaborate with the PCTU. Day to day admin within the unit covers tasks such as:
- Filter enquiries to the unit, liaising with unit staff as necessary
- Maintain records of all agreements between CIs and PCTU
- Maintain database logging PCTU activity
- Maintain database of active and completed projects supported
- Administrative support for supported projects includes design and maintenance of trial websites for all supported projects.
Further administrative support can be arranged (mainly for trials led from within the Centre for Primary Care and Public Health) to include for example trial correspondence, liaising with research staff or setting up site files as required.
PCTU statisticians: Lauren Bell; Lee Beresford; Claire Coleman; Gordon Forbes; Lauren Greenberg; Brennan Kahan; Vichithranie Madurasinghe; Nadine Marlin; Claire Nightingale; Neil Wright
Statistical support is required at all stages of a project starting with input into protocol development. Further support includes developing analysis plans, performing randomisation or minimisation for trials, liaising with health economist and data managers working on trials, or other studies under the remit of the PCTU, to ensure appropriate data management systems are in place and of course carrying out statistical analyses. Other tasks performed by the statisticians are:
- Carry out sample size/power calculations
- Input into CRF/data capture tools development
- Write detailed statistical analysis plans
- Liaise with data manager to ensure adequate cleaning of final dataset
- Write and check Stata .do files or other appropriate programmes to perform data manipulation and analysis
- Produce reports for the Data Monitoring Committee, Trial Steering Committee or funder as necessary
- Perform any pre-planned interim analysis blinded to treatment allocation. If unblinded analysis is necessary, such analysis will be performed by another statistician in the PCTU.
- Attend trial/study team meetings where possible
- Liaise with data manager and trial manager throughout the duration of the trial to ensure data quality and integrity
- Write a final statistical report
- Authorship on publications arising from projects
- Respond to publication reviewers' comments.
Trial coordinator / Trial manager
PCTU trial managers and coordinators: John Allotey; Sybil Bannister; Lesley Dibley; Julie Dodds; Jessica Gavira; Eion Golden; Wai Yee James; Paula John; Doris Lanz; Bev MacLaughlin; Jacqueline Mansfield; Katie Myers-Smith; Sian Newton; Hana Pavlickova; Sarrah Peerbux; Anna Placzek; Ewelina Rogozinska; Irene Simmonds; Sarah Snuggs; Natasha Stevens; Shiva Taheri; Ann Thomson; Jenn Walker; Karolina Witt
The trial coordinator or manager will maintain general oversight of trial coordinating participating sites as necessary over the full duration of the project. They also manage the trial administration by ensuring that files and documentation is up to date and complete, by keeping accurate written and computerised secure and safe records. They will ensure that all clinical trials procedures are fully compliant with the PCTU's and sponsor's standard operating procedures as applicable to the trial.
They will act as the point of contact for all external and internal agencies and provide efficient day-to-day management of the trial.
This includes but is not limited to:
- Maintain confidentiality and security of patient and staff records
- Recruitment, retention, training, appraisal and supervision of trial team members.
- Establish procedures to ensure adherence to trial protocols and administrative requirements
- Ensure the timely recruitment of trial participants with secure randomisation processes and subsequent efficient and effective data management
- Monitor the trial progress to ensure compliance with and adherence to the project plan and to identify, evaluate and rectify problems
- Manage the trial budget(s) and maintain the accounts
- Coordinate the preparation and publication of data, reports and information, ensuring that these meet legislative, contractual and ethical requirements
- Liaise with the Trials Steering Committee and Data Monitoring and Ethics Committee with a particular view on compliance with Research Governance, Good Clinical Practice, Data Protection and Ethical Requirements
- Provide regular and ad hoc information, both written and verbal, to all the trial participants, funders and sponsors. This could include reports, updates, guidance, proformed commitments and, possibly, a Newsletter.
- Work with the Chief Investigator to ensure that the trial is meeting its targets, is producing meaningful output and to predict and plan any changes that warrant requests to changes in protocol, funding or time
- Ensure the inclusion of patient representatives at the appropriate levels and times
- Plan and support meetings and work of the various groups and bodies associated with the trial.
The trial coordinator will also have access to additional advice and assistance from the PCTU's senior trial manager as well as the quality assurance officer. This will be particularly relevant at approval stage, when liaising with various external agencies to gain the appropriate approvals for the project, and in the event of any non-compliance or serious adverse events.
PCTU trial monitor: Jeanette Hansen
PCTU will monitor and/or audit PCTU supported CTIMP and non-CTIMP trials on a risk-based basis as agreed by the sponsor. The monitoring plan will be agreed by the CI, sponsor and PCTU QA manager prior to study initiation.
Tasks performed by the monitor are:
- Source data verification
- Monitor progress of trial
- Confirm that all adverse events are being documented and reported as necessary
- Check CI adheres to their responsibilities according to GCP and delegates responsibilities appropriately
- Scrutinize trial related documents
- Examine research staff on their knowledge of the protocol
- Ensure that the trial is being conducted according to GCP, clinical trial regulations and sponsor requirements.
- The purpose is to verify that reported trial data is correct, complete and verifiable (ICH GCP 1.38 and 5.18.1). Findings are reported to the PCTU QA manager and sponsor via a monitoring report.
What PCTU does
What is a clinical trial?
We use the definition of a clinical trial as proposed by the International Committee of Medical journal editors:
"Any research project that prospectively assigns human subjects to intervention and comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome. By 'medical intervention' we mean any intervention used to modify a health outcome. This definition includes drugs, surgical procedures, devices, behavioural treatments, process-of-care changes, and the like."
This definition is wider than other definitions, some of which restrict the use of the word 'clinical' to trials in which medicinal products are being investigated. Many of the trials the PCTU leads and supports are not trials of investigational medicinal products.
What is an investigational medicinal product (IMP)?
Article 2 (d) of the EU Clinical Trials Directive 2001/20/EC provides the following definition for an IMP:
"a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including products already with a marketing authorization but used or assembled (formulated or packaged) in a way different from the authorised form, or when used for an unauthorised indication, or when used to gain further information about the authorised form."
The PCTU does lead and support trials of investigational medicinal products but these are in the minority.
Trials led by the unit
Trials linked to the unit
These include trials led from elsewhere in Barts and The London School of Medicine and Dentistry or Barts Health NHS Trust, and trials led from outside these organisations. The last category includes multi-centre trials led from other centres, where the unit may sometimes have joint responsibility for aspects of trial design and analysis together with another clinical trials unit. Trials from outside the Centres of Primary Care and Public Health and Psychiatry can be linked to the unit if they are trials of effectiveness fitting broadly with either the research strategies or methodological interests of the unit.
How to obtain support
The initial request has to be received at least 12 weeks before the intended application's submission date (outline application if applicable).
Level of support
Usually, the PCTU would expect to provide all the services listed under details of support available, dependant on the potential costs for support and the capacity of the PCTU. In some cases the level of support will depend on the costs involved and the capacity of the PCTU. We are able to offer bespoke advice tailored to the individual needs of each supported project but will only engage in high quality, methodologically sound trials where we also have academic input. All trials supported by the PCTU must adhere to relevant Standard Operating Procedures already in place.
Once the trial chief investigator and the PCTU manager are in agreement about the level of support and costs, approval for support must be gained in writing (usually by email) from the PCTU director or manager. This approval must be gained before any funding applications are submitted and must include full details of the support and cost agreed upon.
Support can be accessed during protocol development and during the trial itself. Support accessed during protocol development is not charged for and must be negotiated depending on PCTU capacity. This support is important in relation both to successful funding and successful projects and we encourage all researchers to take full advantage of the support offered this stage.
We often encourage researchers to also link with the London Research Design Service for further support in developing their application.
Services accessed after trial funding is secured must all be adequately costed and agreed beforehand. We will expect to recover the true costs of our engagement in a study in terms of staff costs and consumables.
Such funding supports staff employed by the unit to work across a range of trials, such as data managers, statisticians, health economists, quality assurance officers, administrators and the unit manager.
Areas in which the unit supports trial are:
In protocol development
- Statistical advice prior to submission
- Advice about sample size calculation
- Advice about statistical analysis plan in protocol development
- Advice about trial design
- Other field specific advice about:
- health economics analysis
- data management
- quality assurance
At Set up and during trial
- Randomisation service
- Statistical Services
- Statistical analysis planning
- Statistical advice and analysis
- Contribution to report writing
- Data Management
- Data management advice
- Database set-up
- Quality Assurance
- Advice on adverse event reporting
- Advice on clinical trial regulatory requirements and quality assurance
- Access to and advice about CTU endorsed SOPs
- Health Economic Services
- Economic evaluation
- Contribution to report writing
- Administrative support
- Senior Statistician advice and presence on steering committees
- Senior Health Economist advice and presence on steering committees
- Senior trial management advice
- Trial coordinator support
- Trial monitoring
The unit does not provide advice that can be accessed elsewhere. For trials led from Barts and The London School of Medicine and Dentistry, detailed advice about research governance, ethical approval and MHRA procedures please see Joint Research Management Office (JRMO) of Barts Health NHS Trust and Queen Mary, University of London.
The chief investigator is responsible for negotiating level and cost of support and for gaining approval for support by the PCTU (as specified in PCTU support), and for clearly specifying the role of the PCTU and corresponding financial implications in any funding application.
The PCTU works to a number of SOPs specific to the PCTU. The chief investigator is responsible for ensuring that trials linked to the PCTU follow these SOPs. Compliance will be monitored by the PCTU. The responsibilities of the chief investigator as detailed in the ICH Good Clinical Practice guidelines are listed below:
- Qualifications and agreements (GCP, delegation of trial-related duties)
- Adequate Resources – time, funding, demonstrate ability to recruit (via pilot etc)
- Medical care of trial subjects
- On-going communication with REC/MHRA throughout trial (amendments, annual reports etc)
- Ensure full compliance with protocol and document deviations and submit amendments to REC
- Investigational Product (if applicable) - responsible for IMP accountability at site/s (can be assigned to appropriate pharmacist)
- Randomization Procedures and Unblinding – responsible for following trial's randomization and blinding/unblinding procedures (if applicable)
- Informed consent – responsible for following GCP guidelines on informed consent
- Records and Reports – follow GCP guidelines on CRF and source documentation, maintenance of trial documentation, financial agreements and archiving
- Progress Reports – provide written summaries to REC (annually or more frequently if requested) and sponsor and REC regarding substantial changes to trial
- SAEs - responsible for ensuring all SAEs reported to sponsor (‘Sponsor’ is an individual, company, institution or organisation which takes responsibility for the initiation and management of the clinical trial)
- Premature Termination or Suspension of Trial – Responsible for ensuring trial subjects, institution sponsor and REC are promptly informed if trial ends prematurely or is suspended
- Final Report – ensure that final report provided to institution, REC, regulatory authorities and sponsor
Standard Operating Procedures
- PCTU SOP DM 02 CRF Design v2.0
- PCTU SOP DM 04 Data Entry, Quality Control, Data Extraction and Database lock v2.0
- PCTU SOP DM 05 Electronic Data Security v3.0
- PCTU SOP DM 06 eCRF-Database Application Design and Development v2.0
- PCTU SOP DM 07 Database Validation v2.0
- PCTU SOP DM 08 Database Application Versioning and Change Control v2.0
- PCTU SOP DM 09 Business continuity - Backup and disaster recovery v2.0
- PCTU SOP DM 10 Database Application Documentation v2.0
- PCTU SOP DM 11 Data Transfer v2.0
- PCTU SOP GA 01 PCTU Trial Support Proceedure (for CIs) v5.0
- PCTU SOP GA 02 PCTU Filtering System for Trial Support Enquiries (PCTU Staff) v5.0
- PCTU SOP GA 03 Event Organising v3.0
- PCTU SOP GA 04 Agreement between PCTU and JRMO regarding costing of PCTU v2.0
- PCTU_SOP_HE 01 Health Economics Analysis v3.0
- PCTU_SOP_IT 01 Clinical Trials Systems Access v2.0
- PCTU SOP QA 01 Pragmatic CTU SOPs v4.0
- PCTU SOP QA 02 QA and QC System v6.0
- PCTU SOP QA 03 Document Control v5.0
- PCTU SOP QA 04 Monitoring of PCTU Supported Research Projects v2.0
- PCTU SOP QA 05 Statistical and Health Economic Analysis QC v2.0
- PCTU SOP QA 06 Staff Training v3.0
- PCTU SOP QA 07 Preparing for regulatory inspections v1.0
- PCTU SOP SP 01 Statistical Analysis v4.0
- PCTU SOP TC 01 Trial Close Out v2.0
- PCTU SOP TC 02 Archiving Research Projects v3.0
- PCTU SOP TM 01 Trial Master File and Investigator Site file maintenance v6.0
- PCTU SOP TM 02 External Trial Oversight Committees v3.0
- PCTU SOP TM 03 IMP management and labelling v4.0
- PCTU SOP TM 04 Informed Consent v2
- PCTU SOP TM 05 Adverse Event Reporting for CTIMPs v2.0
- PCTU SOP TM 06 Adverse Event Reporting for non-CTIMPs v2.0
- PCTU SOP TM 07 Document Completion, Transport and Storage v2.0
- PCTU SOP TM 08 Reporting of Amendments and Deviations v2.0
- PCTU SOP TM 09 Site Initiation and Staff Training v3.0
- PCTU SOP TM 10 Handling Trial Correspondence v2.0
- PCTU SOP TM 11 Effective Trial Management v3.0
- PCTU SOP TM 12 Annual progress, safety and end of trial reports v3.0
- PCTU SOP TP 01 Protocol development v4.0
- PCTU SOP TP 02 Statistician Involvement v5.0
- PCTU SOP TP 03 Randomisation and blinding v5.0
- PCTU SOP TP 04 Clinical Trial Risk Assessment v2.0
- PCTU SOP TP 05 Trial Management - The Approval Processt v2.0
Pragmatic Clinical Trials Unit
c/o Centre for Primary Care and Public Health
Yvonne Carter Building
58 Turner Street
Whitechapel, London E1 2AB
Telephone: + 44 (0)20 7882 3449
Facsimile: + 44 (0)20 7882 2552
Please note the PCTU does not recruit trial participants. If you wish to participate in any of the trials we support please contact the trial team directly. For contact details see trial information in our research section.
Inside a Clinical Trials Unit
This course will be of interest to new principal investigators and other researchers who have not previously worked closely with a Clinical Trials Unit (CTU), and who want to learn more about the design and conduct of pragmatic clinical trials and the nature of CTU involvement. The course is an immersive experience including observation of real-life trial processes and the work of CTU staff, and one-to-one time spent with knowledgeable tutors.
Registration on one of our 3-day taught courses (Introduction to Design, Conduct and Analysis of Pragmatic Clinical Trials, or A Practical Guide to Cluster Randomised Trials (Introductory Course)) is also included in the price. The course will be based at the Pragmatic Clinical Trials Unit (PCTU) at Barts & The London School of Medicine & Dentistry.
In addition to the 3-day taught course, the total time commitment amounts to no more than 1 hour a week, spread over a period up to one year, though this can be scheduled flexibly to suit your needs. You will benefit from:
- a lead tutor who will be your main point of contact with PCTU, who will help you to plan a series of opportunities (at least 10 hours in total) for observing meetings and other PCTU activities encompassing the complete natural history of a trial;
- 6 one-to-one 1-hour sessions with your lead tutor, spread over the year, to consolidate what you have learned and discuss issues in depth;
- 6 one-to-one 1-hour sessions, spread over the year, with a specialist tutor from one of four PCTU teams (depending on the area you particularly want to focus on): statistics, data management, quality assurance or trial management.
Some of your time will be devoted to self-directed learning: your lead tutor will give you resources and practical tasks suited to your study programme, and there will be space in PCTU for hot-desking and engaging more fully with the Unit.
You can start the course at any time during the year, but the number of places at any one time is very limited, and you will need to give us at least 1 month’s notice of your intended start date, so we advise that you contact us as early as possible if you are interested in joining.
Cost for those booking before end of June 2016:
QMUL staff: £2,500
CONTACT (also for information about our 3-day taught courses, including dates)
Current developments in cluster randomised trials and stepped wedge designs
This meeting will consist of a series of short talks and discussion about new perspectives for the design, the analysis and the reporting of cluster and stepped wedge trials.
We will reply with decisions regarding abstracts by Sept 29th 2016.
Old Library at Queen Mary University
29th November 2016: 10:30am-4pm
Link for online registration and payment:
Registration ends: 14thNovember 2016
Cost: £25 includes Lunch
30 June 2015 - Prof Sandra Eldridge awarded Honorary Fellowship of Royal College of General Practitioners
A Practical Guide to Cluster Randomised Trials in Health Services Research
Sandra Eldridge and Sally Kerry have published a book 'A Practical Guide to Cluster Randomised Trials in Health Services Research' with Wiley & Sons Ltd. The book provides a concise guide to running cluster randomised trials in a health care setting; covering ethics, recruitment, piloting, design, reporting, systematic reviews, process evaluations and monitoring with introductions to analysis, sample size calculations, and health economics. The book is available to purchase from Wiley.