HaBio publication No 1 August 2018
Sutton AJ, Lamont JV, Evans RM, Williamson K, O’Rourke D, Duggan B, et al. (2018) An early analysis of the cost-effectiveness of a diagnostic classifier for risk stratification of haematuria patients (DCRSHP) compared to flexible cystoscopy in the diagnosis of bladder cancer. PLoS ONE 13(8): e0202796. https://doi. org/10.1371/journal.pone.0202796
HaBio status June 2017
Once again we would like to thank all the patients who agreed to take part in HaBio. Without their participation and the support of their families, HaBio would not have been possible.
HaBio is investigating the use of protein measurements as risk stratifiers for patients who present with blood in the urine. Risk stratification will help doctors to correctly identify patients who require urgent cystoscopy.
We are currently finalising the entry of the data into the bespoke database. For each of the 674 patients an extensive medical history was collected at their time of recruitment. These data included smoking and occupational histories together with relevant clinical data. Subsequently, a review of each patient’s clinical record was undertaken by a consultant urologist (Mr Brian Duggan) to ascertain the cause(s) of haematuria for each patient. For some of the patients recruited to HaBio no underlying cause was found and their diagnosis was recorded as “no diagnosis”. For the remaining patients the underlying causes ranged from low risk causes such as infections to more serious diseases. Follow-up for each patient recorded relevant diagnoses, treatments and outcomes since the time that each patient was recruited. Follow-up was completed by the HaBio Clinician, Mr Mark Evans.
HaBio is the follow-on study from a trial published, following peer-review, in Cancer in 2012 (https://www.ncbi.nlm.nih.gov/pubmed/21918968). This publication described how collectives of protein measurements could distinguish patients with serious conditions from those with low risk conditions such as infections. One of our first publications will present the HaBio findings in a similar style to the Cancer paper. We plan to submit this manuscript to a high impact journal in November 2017. In addition, we are preparing a manuscript on the cost effectiveness of a diagnostic classifier for risk stratification of haematuria patients. At the end of 2017 we plan to submit data on risk stratification at an appropriate conference.
Kate Williamson has established collaborations within Queen’s University Belfast, with local clinicians and with academics and clinicians abroad. This will ensure that the findings from HaBio are disseminated as appropriate, at scientific and clinical conferences, both locally and abroad; and subsequently published in high quality journals.
Synopsis of HaBio to date
Recruitment to HaBio is in its final phase. To date we have recruited 632 patients. We hope to recruit more than 650 patients before we close recruitment at the end of June 2016. Many thanks to all the patients, their families and all the clinical, nursing and admin staff who have facilitated the recruitment of patients.
We plan to hold a Discussion Forum in the Autumn 2016. At this meeting we will give an overview of the results of HaBio and there will an opportunity to speak to the clinicians who have worked on the study.
We are hoping to recruit a Staff Grade Clinician funded by HaBio and the Belfast Trust in the near future. The successful applicant’s main duties will be follow-up and data interpretation for manuscripts.
We have completed clinical reviews for 557 patients. Randox Laboratories will have completed biomarker analyses on 583 patients by April 15th 2016.
The HaBio database continues to grow. We have recently carried out audits on the biomarkers, smoking characteristics and clinical variables within the HaBio database.
Recruitment to HaBio is now closed
Recruitment to HaBio is now closed. We have recruited 676 patients to HaBio since 15th November 2012. Our last patients were recruited on 28th June 2016.
Our responsibility to these 676 patients is to ensure that their efforts lead to new understanding and better efficacy and efficiency in how patients with haematuria are diagnosed and treated in the future. The clinicians, led by Brian Duggan, will lead in the overall interpretation of the data. The dataset is comprehensive and includes the levels of >50 biomarkers measured by Randox Laboratories. Mr Michael Stevenson will oversee all statistical analyses.
I would like to commend the nurses and the technicians who have evolved pathways to circumvent the many challenges encountered during the recruitment phase of HaBio. They have worked beyond their job descriptions and have made invaluable contributions to the evolution of concepts and ideas. The data they have helped to collate and evolve is stored on a bespoke database set up by Gary Laverty from Randox Laboratories and Steve Stewart from Queen’s University Belfast. Our thanks to the many NHS staff who helped us in Belfast City, Ulster and Craigavon Area Hospitals.
Thanks to those who attended the 30 Clinical Committee meetings, chaired by Ruth Boyd, Northern Ireland Clinical Trial Centre (NICTC). NICTC provided a framework of support and expertise throughout recruitment. At the Clinical Committee meetings long discussions evolved strategies to boost recruitment in a difficult NHS environment. Mr Hugh O’Kane, Clinical Lead, often provided pragmatic solutions to irritating “niggles” that we encountered.
I would like to thank the Northern Ireland Clinical Research Facility (NICRF) who helped us in an effective, friendly and efficient manner. NICRF is an excellent facility, providing a warm welcome to the patients who volunteered for recruitment to our study.
The Northern Ireland Biobank facilitated the construction of tissue microarrays which have been annotated and reviewed by Dr Declan O’Rourke. This resource will help us to increase our understanding of the associations between pathological features and measured biomarkers.
Ms Julie Hunter set up the administration procedures for the study. Julie has advised me, and still keeps me, on the straight and narrow. She created systems for the HaBio documentation and is highly respected by us all.
Thanks to those who have provided support and guidance with respect to ethics and governance and maintaining the integrity of the HaBio study.
Thanks to all of those who faithfully attended our Trial Steering Committee Meetings. The next Trial Steering Committee will take place in September 2016.
10 July 2016
Recruitment has started in Craigavon Area Hospital
We are delighted to report that Leanne McCourt recruited our first two patients from Craigavon Area Hospital on Thursday 17th September 2015. We are very grateful to these two patients and to the many people who have helped us to set-up recruitment pathways in Craigavon Area Hospital. We are now actively recruiting patients at Belfast City Hospital, the Ulster Hospital Dundonald and Craigavon Area Hospital.
Kym’s Reflections for 21st August 2015
Today has been a good day for HaBio:
I finally used up all the large sized gloves so it’s all medium gloves from here on out! Yay!
Laura’s pass for down stairs is finally working (I could see her suppressing a happy dance).
The delegation log for Craigavon is signed and ready to go.
But, most importantly, we have not only made it to 500 but actually 501 patients! So we are officially
half way! Just thought I would share the good news with everyone (I’m particularly excited about the gloves).
Update on HaBio Staff
Julie Hunter left the HaBio team on 28th February 2015 to return to her QUB admin position; having completed her three year secondment. Julie made a very valuable contribution to HaBio. Julie has encouraged us all to conform to her very high standards of record keeping. Julie’s duties will be spread across Gail Carson, Karen Young and Kate Williamson.
Ms Kym Griffin, who has experience in data handling and an interest in animal behaviour, joined the HaBio Team as a technician on 10 March 2015. Kym is well settled in. Laura Maxwell, on secondment from Urology, took up her position as a Clinical Research Nurse (CRN) on 30 March 2015. Laura has already begun recruiting patients.
Brian Duggan has been working hard and has now completed final diagnosis for 298 patients. Recruitment stands at 419 patients. Kym Griffin, Karen Young and Gail Carson have been working on data processing and entry. Approximately 240,000 data entries have been entered and checked.
Karen Parsons left the HaBio team in November 2014. Karen was very hard working and recruited more than 140 patients to the HaBio study. We all miss her, but understand her motivation to enrol in a Queens University Course focussing on urology. She is enjoying the course, saying that she is very busy with many assignments and is building on her practical skills. We are very grateful for Karen’s considerable contribution to HaBio.
HaBio has recruited 400 patients
Today we recruited our 400th patient! We still need to recruit another 599 patients. Fortunately we are very confident that we can do this. The pathways, the people and the recruitment sites are all set-up. Although HaBio is a very strong team comprising people with a wide range of skills, we are very dependent on the help and cooperation from many other people who help us along the way to 999 patients. People such as nurses and doctors, admin staff, secretaries, laboratory staff, people in the wards and clinics, experts in clinical trials, governance, ethics, data processing and analyses and the list goes on……Thank you to all these people and to the patients and their relatives.
We have now recruited >280 patients and we have already collated a very substantive database. Julie Hunter and Karen Young are responsible for the entry of this data onto the HaBio database. They both enter every piece of data for every patient into the HaBio database. Any discrepancies are automatically flagged each week. This double entry ensures the accuracy of the data. The data is stored on a dedicated password protected computer in Queen's University Belfast. All the data is closely monitored by the Chief Investigator, Kate Williamson, who liaises closely with the HaBio clinicians.
Recruitment at the South Eastern Trust
We are delighted to report that we have now started to recruit patients from the Ulster Hospital, Dundonald. To date the Clinical Team have recruited >250 patients to HaBio. Thank you to all these patients and to all the many people who have helped to set up and continue to facilitate recruitment. We will recruit patients from Belfast City Hospital and the Ulster Hospital Dundonald throughout the duration of the HaBio study.
Update on Recruitment
The Clinical Team have recruited >164 patients to HaBio. All these patients were recruited from the Belfast City Hospital. Thank you to these patients. We will continue to recruit patients from the Belfast City Hospital throughout the HaBio study. In addition, we are hoping to start recruitment at the Ulster Hospital Dundonald in late May 2014. Mr Sam Gray and Mr Brian Duggan are Consultant Urologists in the Ulster Hospital and they have been helping the HaBio clinical team to set up the recruitment pathways. In the autumn of 2014 we will also be recruiting from Craigavon Area Hospital. The Clinical Lead at Craigavon Area Hospital will be Mr Tony Glackin.
Update on HaBio staff
We are delighted to report that we have three new staff on the HaBio team. Ms Karen Young has been appointed as HaBio Technician to cover Gail Carson’s maternity leave. Congratulations to Gail on the recent birth of her daughter, Connie. Karen Parsons and Janine Gill have been appointed as HaBio Clinical Research Nurses. They will be working closely with Mr David Curry (HaBio Clinician) and their main role is recruitment of patients.
The Clinical Team have recruited 77 patients to HaBio. Currently, they are recruiting patients from the Belfast City Hospital site. We are developing pathways for recruitment at the Ulster Hospital Dundonald, Newtownards Hospital and Laganvalley Hospital over the next few weeks. Some patients will be recruited at hospitals in Northern Ireland. Others will attend the Clinical Research Facility in the Belfast City Hospital. Only 922 patients left to recruit!
In a recently accepted for publication in BMC Medicine we demonstrate that when haematuria patients are allowed to cluster naturally on the basis of their individual biomarker profiles the population separates into high and low risk subpopulations. This finding has obvious implications for risk stratification of patients presenting with haematuria. Two students undertaking projects for their honours BSc contributed to this paper. The students, Lisa White, now a PhD student, and Owen Roddy, now a medical student, acquired understanding of the Systems Biomedicine approach that was applied to analyse the extensive biomarker dataset that was collected from 157 patients with haematuria. Using random forest classifiers and agglomerative clustering we were able to focus on collectives of biomarkers, rather than individual ones. Our results highlight the way that biomarkers cluster on the basis of their collective biological behaviour as functionally related proteins.
In a paper recently published in Cancer we describe how we defined a classifier for bladder cancer diagnosis that was based on clinical and demographic data. We then investigated whether addition of biomarkers to this classifierIn the context of HaBio, a classifier would enhance its accuracy. Although, the numbers of patients in this pilot study were insufficient for separate test and evaluation groups, we were able to detect a significant improvement in the AUROC statistic from 0.76 to 0.90. Therefore we are optimistic that multivariate classifiers derived from the data that will be collected in HaBio will achieve the accuracy required to inform triage decisions.