Clinical Practice Research Datalink courts potential users

We received on Friday our invitation to the Clinical Practice Research Datalink (CPRD) Users Meeting that will be held at the MHRA offices in London on 24th May 2012, consisting of a series of short presentations by representatives of CPRD and external partner organisations to give "further insight, and an opportunity for input, into the current and future aims of CPRD."

The background we have covered severally before (see here and here): "CPRD is the new English NHS observational data and interventional research service, jointly funded by the NHS National Institute for Health Research (NIHR) and the Medicines and Healthcare products Regulatory Agency (MHRA). It combines the piloting work of the Research Capabilities Programme (RCP) and the existing General Practice Research Database (GPRD)."

CPRD services are designed to maximise the way anonymised NHS clinical data can be linked to enable many types of observational research and deliver research outputs that are beneficial to improving and safeguarding public health. CPRD will act to provide services to a wide range of researchers and the aim of the Users Meeting will be to ensure that its plans meet the needs of the broad cross section of researchers in academia, the NHS and commercial companies both in the UK and globally.

The specific topics that will be covered on the day include:

• Pragmatic and Phase III - IV clinical trials
• Multidimensional data quality
• Hospital prescribing data
• Models for linkage
• Disease and patient group data marts

The day will provide "several opportunities for potential users to raise and discuss their priorities and requirements" to ensure CPRD meets researchers' needs.

It is possible that we won't be able to attend ourself so if any of our readers are planning on going along, let us know and we'll get in touch to see if you want to post some feedback on these pages!

Clinical Practice Research Datalink is finally here - or is it?

The new Clinical Practice Research Datalink about which we have blogged much in the past has finally arrived (http://www.cprd.com/intro.asp) amid a certain amount of fanfare - see this from Pharma Times, this from PMLive and this from GP magazine.

 You may notice that the GPRD pages now redirect to this site and to a certain extent, this is largely a rebranding exercise at the moment. Behind the scenes a team at the DoH are trying to ensure that major data sources are willing and able to engage with this initiative but the speed at which they come online remains to be seen. We'll fill you in further on plans for a researchers data-catalogue interface as this project advances - and if CPRD are not offering that just yet, perhaps the MRC are - we'll get you up to date with the MRC's Data Support Service before the week is out.

Patients' views on participating in medical research - Part 1: Attitudes

While we are still working on our 'Funders' Policies on data sharing' article we decided to post here a summary of recent work on patients' attitudes to participating in medical research - again, a primer on the current state of play in clinical research in the UK selecting choice elements from recent reports; check out the footnotes for interesting sources to follow up. Part 2 will cover Engagement and Participation and will be followed by a piece on medics' attitudes to research. As always, let us know what you think - if there are more recent / complete / credible studies out there which draw different conclusions, let us know!

We also came across a tweet today from Simon Denegri linking via his blog to an NIHR site containing video testimonials of the experiences of patients, nurses and doctors taking part in or working on clinical trials which is worth a look too. Apologies for the bizarre formatting of the bullet-points below!

Attitudes

The following bullet points are extracted from the text of the report “The Use of Personal Health Information in Medical Research General Public Consultation” which presents the the findings of a programme of research carried out among the general public by Ipsos MORI on behalf of the Medical Research Council (MRC) published in July 2007 with the aim of “Identifying public concerns and misconceptions surrounding the secondary use of personal health information for medical research.”

In summary they found that there was low public awareness of medical research, that the public were in general supportive of research when informed about it and when they felt in control of their data – but continue to have reservations about privacy:

·         “The advantages of medical research are seen by the public to far outweigh the disadvantages. Seven in ten feel the merits of research outweigh the disadvantages, compared to only 6% who say the opposite.”

·         The qualitative phase of this consultation showed that there was little public awareness and understanding of medical research (and thus the use of secondary health information for medical research purposes), who undertakes it and to what ends.

·         “The workshops indicate that, if the public is informed about what medical research entails, they are generally positive towards it. Communications are key to building public trust… Key to effective communication on the subject is the need to keep terminology simple.”

·         The quantitative phase of the research showed that “Just over a third (34%) cannot think of any associations with the phrase personal health information, which indicates fairly low awareness for the MRC to address.”

·         “Perceptions of who, or which organisations people feel would hold personal health information focus mainly around the health service [GPs, hospital doctors and the NHS]. Medical researchers (working in any capacity) are mentioned by less than 1% of the general public.”

·         “If the public feels in control of their information and its potential uses, then they are likely to be more inclined to allow their personal health information to be used for medical research purposes…The qualitative research shows that the main public concerns are over organisations sharing this information, particularly for commercial gain…. Medical researchers working in the public sector i.e. for Government and universities (both trusted by 11%) are more trusted than their counterparts working for private companies (4%). The private sector features prominently among the least trusted organisations where personal health information is concerned.”

·         “While most see the benefit of personal health information being used for medical research purposes, the very same people can hold reservations over the implications for privacy…. The most common reason for being unlikely or certain not to allow personal health information to be used for medical research purposes is concern over privacy (28%).”

·         “The two key pillars of anonymity and consent feature highly in the debate over what information should be available, to whom, and in what circumstances. These two themes are central to building trust.”

·         “The vast majority (87%) trust GPs to have access to their personal health information, and over half trust other health professionals – such as consultants or hospital doctors (59%).”

·         The public needs “a human face to reassure them and discuss the issues around consent and confidentiality with them. Health professionals in general, and GPs in particular, are the most trusted to perform this role. For many, the GP’s surgery is the most frequent point of contact on health issues and it would seem sensible to use this as one location for dissemination of information about personal health information for medical research purposes.”[1]

The Academy of Medical Sciences presented a review of public engagement on the use of patient data, summarising several reports thus:

·         NHS Connecting for Health – Using patient information in the NHS (2009).98 This report found that the 96 participants were generally happy for their data to be used in research as long as anonymity was ensured and they were approached by someone they knew and trusted, such as their GP.

·         Royal Academy of Engineering –Young people’s views on the development and use of Electronic Patient Records (201099) Of 3,000 young people surveyed, most were not against the idea of anonymised data being used in medical research; 50% said that they would want to be asked for consent each time researchers used their anonymous record.

·         New Economics Foundation - Exploring public views on personal electronic health records (October 2010100) Surveyed 6000 people and found: that 57% of adults and 67% of young people were enthusiastic about the benefits of switching to digital patient records; and that patient consent would be essential for using identifiable data for research.

·         Wellcome Trust/University of Surrey – Public Attitudes to Research Governance (2006). Based on interviews and focus groups with 89 people; the report found participants were willing to provide personal data for biomedical research providing its use had been explained to them. Concerns remained over whether promises of anonymity and security could be fully relied on.

·         MRC/Ipsos MORI - The Use of Personal Health Information in Medical Research (2007). Interviewed a sample of 2,106 UK adults and found that 69% were ‘likely’ to allow the data to be used for health research purposes

·         Academy of Medical Sciences - Personal data for public good: using health information in medical research (2006). Consulted with a wide range of patient representatives and found research using personal data was strongly supported. Public engagement was identified as one of the most important tasks in developing future arrangements for appropriate governance for the use of health information in health research.[2]

Another 2007 report, a survey of literature covering public and professional attitudes to privacy of healthcare data commissioned by the General Medical Council and conducted by Cambridge Health Informatics, came to the following conclusions:

·         Assessment of public attitudes is dependent on how the topic is framed. People will express concerns if questioned about ‘concerns’, but will readily trade these ‘concerns’ for health  or other benefits, even altruistic ones.

·         ‘Real world’ choices can be very different (and constrained) from those offered in opinion surveys where costs and trade-offs may not appear.

·         Public attitudes are not uniform and the surveys suggest that they are often either ill-informed or unformed (or sometimes formed during an investigation or discussion).

·         Attitudes among the public vary from the completely unconcerned to a small proportion of the public that has strong views on privacy, either from a sense of a ‘right to privacy’ or because of some sensitive episode in the past that they wish to protect. The majority of the public seem to rely on trust in clinicians and the healthcare system.

·         It is clear that the public (and to some degree the professions) are unclear on the potential roles of medical records in modern healthcare.

·         The public would like a choice in the use of their records, but there is little hard evidence about what arrangement of choices the public would generally prefer – or whether there are radically different opinions on this.

·         The public appear to be becoming more comfortable with computer technology, which may reduce fears over privacy, but with increasing expectations over security and choice about access to their records.[3]

Of note these authors contend that “Generally much of healthcare policy in relation to the privacy of healthcare data has been based on historic ethical and legal considerations together with financial practicalities rather than on an evidence-base of what individuals would want or expect.  This has been, in part, been due to a perceived lack of understanding by the public at large (and many professionals too) of how medical records are actually used and shared within the healthcare system as a whole: this perception means that they have rarely been asked in any formal consultative way.”

They also contend, however, that “Establishing public concerns about the privacy of health data poses problems because, from the few surveys that have been performed, it appears that only a small proportion of the public have a strong opinion and fewer still have an understanding of the complex issues that need to be weighed up when arriving at an opinion.”[4]

---

[1] Ipsos MORI on behalf of the Medical Research Council: The Use of Personal Health Information in Medical Research General Public Consultation [2007]

[2] Ibid. Full citations for these reports are:

UK Clinical Research Collaboration (2010). Attitudes and awareness amongst General Practioners (GPs) and

patients about the use of patient data in research – a study by the UK Clinical Research Collaboration Board

Sub-Group on Public Awareness. UCKRC, London.

NHS Connecting for Health (2009). Using patient information in the NHS.

http://www.connectingforhealth.nhs.uk/engagement/public/consultations/hsreport.pdf

Royal Academy of Engineering (2010).Privacy and prejudice: young people’s views on the development and

use of electronic patient records.

http://www.raeng.org.uk/news/publications/list/reports/Privacy_and_Prejudice_EPR_views.pdf

New Economics Foundation (2010). Who sees what? Exploring public views on personal electronic health

records.

http://www.neweconomics.org/sites/neweconomics.org/files/Who_Sees_What.pdf

Wellcome Trust/University of Surrey (2006) Public attitudes to research governance: a qualitative study in a

deliberative context.

http://www.wellcome.ac.uk/stellent/groups/corporatesite/@policy_communications/documents/web_document

/wtx038443.pdf

Medical Research Council/Ipsos MORI (2007). The use of personal health information in medical research.

http://www.mrc.ac.uk/consumption/idcplg?IdcService=GET_FILE&dID=10983&dDocName=MRC003810&allowI

nterrupt=1

Academy of Medical Sciences (2006). Personal data for public good: using health information in medical

research. http://www.acmedsci.ac.uk/download.php?file=/images/publication/Personal.pdf

[3] Cambridge Health Informatics report for the General Medical Council: Public and Professional attitudes to privacy of healthcare data - A Survey of the Literature; http://www.gmc-uk.org/GMC_Privacy_Attitudes_Final_Report_with_Addendum.pdf_27007284.pdf

[4] Cambridge Health Informatics report for the General Medical Council: Public and Professional attitudes to privacy of healthcare data - A Survey of the Literature; http://www.gmc-uk.org/GMC_Privacy_Attitudes_Final_Report_with_Addendum.pdf_27007284.pdf

Response to the National Cancer Intelligence Network's consultation: Building an e-health research infrastructure for cancer

Today is deadline day for responses to the National Cancer Intelligence Network's (NCIN) consultation: Building an e-health research infrastructure for cancer (see our blog entry for a list of their proposals).

We have submitted a response from the perspective of those who have worked with data supporting basic and translational research - we'll also be posting later a link to the NCIN and Department of health publication from December last year: An Intelligence Framework for Cancer - but for now, here's how we replied to the consultation:

The UK is currently supporting or considering the development of several initiatives seeking to promote the skills and infrastructure necessary to carry out health research based on linked large-scale or population-level datasets generated through routine processes of data collection.

In Wales, the Health Information Research Unit at the University of Swansea maintains the Secure Anonymised Linkage System (SAIL); in Scotland, the Scottish Health Informatics Programme (SHIP) supports the “collation, management, dissemination and research analysis of anonymised Electronic Patient Records”; in the UK, the Research Capability Programme of the National Institute for Health Research have piloted a Health Research Support Service which is due to be formally implemented as a full service:  the Clinical Practice Research Datalink. The Medical Research Council also recently issued a call for e-Health Informatics Research Centres to “maximise the health research potential offered by linking electronic health records with other forms of routinely collected data and research datasets”.

Of the National Cancer Research Institute partners’ 2010 funding, however, over 50% was spent on research which could be described as basic, translational or early stage; 40% on Biology and Aetiology alone; and some proportion of the discovery and development elements of spending under Common Scientific Outcome (CSO) 5 (Treatment), technology development and evaluation under CSO 4 (Early Detection, Diagnosis and Prognosis), and CSO7 (Scientific and Model Systems) can be ascribed to these types of research.

The infrastructure used to support this work is in many cases intra-institutional, in some inter-institutional, rather than national – although with appropriate standardization, integrated datasets from within institutions could be submitted to national-scale repositories with greater ease. Completeness, accuracy and granularity of the data are vital for this research. Often the data which support and contextualize observations in the laboratory during these research projects are drawn from multiple hospital systems and collated with difficulty. This has an impact on timescales and the validation of observations. Some proportion of the NCRI partners’ spend in each of the CSOs is dedicated to Resources and Infrastructure (R&I) which may include informatics, however, if we look at the other project types falling under R&I for e.g. CSO 4 (Early Detection, Diagnosis and Prognosis) we may reasonably conclude that the proportion dedicated to informatics is not the majority – closer analysis of the NCRI CaRD database is required to confirm this.

CSO4.4 Examples of science that would fit: ·         Informatics and informatics networks; for example, patient databanks ·         Specimen resources (serum, tissue, images, etc.) ·         Clinical trials infrastructure ·         Epidemiological resources pertaining to risk assessment, detection, diagnosis, or prognosis ·         Statistical methodology or biostatistical methods ·         Centers, consortia, and/or networks ·         Education and training of investigators at all levels (including clinicians), such as participation in training workshops, advanced research technique courses, and Master's course attendance. This does not include longer term research based training, such as Ph.D. or post-doctoral fellowships

The MRC, in their call for e-Health Informatics Research Centres, adduce the key findings of the ABPI and UK research funders mapping exercise reviewing the UK capability in e-Health records research – a number of these can be applied to the intra-institutional situation:: institutions could be submitted to national-scale repositories with greater easeics is not the

·         There is a shortage of people with the breadth of skills necessary to carry out the complex linkage and analyses required in health informatics research.

·         There is an absence of career structure in enabling roles such as data managers, software engineers, informaticians and data analysts.

·         There are no clear interfaces between researchers and industry, policy makers or the NHS and there is no ready means for sharing best practice.

Certainly, my own experience of supporting even institutes with strong reputations for research is that they lack the skills, focus and confidence in informatics to make much progress in the development of their infrastructure – and have been extremely glad of the opportunity to take advice and receive support from experienced individuals with a research and informatics background.

Perhaps the NCIN could consider devoting some resource to skills development in this area, disseminating the acquired expertise and knowledge of the NCIN of best practices in data management and handling and the use of technology. Might this sit alongside the work currently envisaged by Proposal 6 of the consultation?

_________

During a meeting with Oracle at the end of last year, an ex-colleague who specialises in molecular and gynaecological oncology suggested that their institute would not be seeking data integration services and infrastructure supply from the likes of Oracle with such urgency if they felt they could get ‘stage and grade’ at diagnosis from the Thames Cancer Registry.

The paucity of staging data in the registries is an established weakness as discussed in the NCIN and Department of Health document, An Intelligence Framework for cancer and steps are being taken to address this, however, the perception of the inadequacy of the dataset collected by the Thames Cancer Registry (and by extension, despite shining examples such as the ECRIC, the amalgamated registries’ dataset) extended beyond the known weaknesses unfairly to the dataset as a whole in the case of this Professor. Such perceptions were not uncommon at that centre and need to be overturned.

The vastly extended dataset which will be collected by the registries in future sounds extremely promising in its potential to support not only epidemiological and population-level research, but also basic and small-scale clinical research. It will be vital, however, to create a sustained ‘sales’ initiative to establish a new level of confidence in the data in the areas of the research community who have hitherto not engaged with these datasets due to the concerns described in An Intelligence Framework. Their concern may be that where a smaller dataset was found wanting, will the collection of a larger one not push already stretched resources beyond their elastic limit?

Having had first-hand experience of the way in which MDT data is fed into the Somerset system and the ample opportunities, often taken by overburdened MDT co-ordinators, to introduce error – it is inspiring to see that a truly modern approach to data extraction and aggregation is being implemented as described by Dr. Rashbass at, to give one instance, the NOCRI Information Systems Workshop.  As described by Dr. Rashbass, various technologies including natural language querying will take data from pathology full-text reports, from local imaging systems and myriad other systems to create the amalgamated national dataset – and this data will be quality controlled and assured. More information on how the latter will be achieved would be welcome.

Similar initiatives and technologies are being employed by healthcare delivery and research organisations themselves – for example, the ORIS oncology platform being implemented intra-organisationally by King’s Health Partners and the Acropolis platform being implemented inter-organisationally. It is important to note that these implementations may be beyond the budget of smaller organisations who deliver oncology services and conduct research – and here the value of a new ‘high-resolution’, quality assured, timely dataset such as that envisaged by the registry modernisation team will have the potential to deliver enormous benefit.

But this will depend on the quality of the data and ensuring that this quality is recognised in the research community. “This service will ensure that common standards and working practices are applied to data extraction, linkage and quality assurance to both national feeds and a range of local sources.” This assertion really needs to be backed up with a strong communications and ‘marketing’ effort.

To this end, should the NCIN devote some resource to support activities at the provider end of the process to ensure that where providers are implementing their own data infrastructures, these can interface with and provide bulk data to the unified registries to the appropriate standard; and where they are not yet capable of developing their own infrastructures, that they have support in the provision of accurate and complete data to the registries and potentially support in the process of designing their own data architectures and integration solutions; and then to effectively communicate the work that they are doing to improve registry data effectively to the community – concentrating not on the sophisticated use of technology to capture and amalgamate data, but on the procedural changes being implemented to assure quality?

Many of the proposals made in the consultation document might be realised by the same infrastructural components – and many of these components are similar to those which will hopefully be implemented by the Clinical Practice Research Datalink (CPRD). Where respondents to the consultation indicate that the proposed data linkage and notification services would deliver great benefit to their work, it may be worth establishing what level of awareness they have of the CPRD, the concern being that the overhead involved in creating facilities which might duplicate some aspects of the CPRD could be enormous given the proportion of the budget for the latter initiative devoted to infrastructure. There might be a greater return on investment to be had by focusing on data rather than infrastructure at the national level?

In conclusion, it might be worth considering if Proposal 6 (a research support service advising on the availability of and access to data) could benefit from being expanded to include some work looking at supporting data quality and intra-institutional infrastructural development -  and engaging the basic and translational research communities to overturn perceptions about the ability of the dataset to support their work.

Let us know what you think - are we way off-beam?

Research Capability Programme's Health Research Support Service - UCL report on the Pilot's effectiveness in Primary Care

Happy New Year and apologies for our lack of recent posts - we're back with some interesting stuff in the pipeline on data integration platforms for service delivery and research (Oracle, Orion, OpenClinica, IBM, Cerner etc.) coming tomorrow.

For now, we should direct you to University College London's report on the "Health Research Support Service Pilot in Primary Care: facilitators and barriers to successful implementation at a national level" - an independent evaluation.

The report contains good feedback from key stakeholders including many patients from the GP practices involved in the Primary Care part of the Pilot. If you're not aware of the aims and status of the National Institute for Health Research's Research Capability Programme and the Pilot Health Research Support Service, check out our links to them and our notes on the Clinical Practice Research Datalink which will take the service forward.

Amongst the key observations from the UCL report were:

On the sample group:

"There were only two practices involved in the pilot and these were strong research practices.  This means the practice staff were used to dealing with research projects and the patients were aware of research, even if they had not previously taken part in it.  Moreover the patients who participated were self-selected and were generally older and educated to a high level.  It may be more difficult to engage both staff and patients in non-research practices."

On patient attitudes:

"There was widespread support for the concept of the HRSS.  The vast majority of patients stated that they felt the HRSS was a good idea and a number highlighted potential benefits that they felt the HRSS would bring about. 'Giving something back’ to the NHS emerged as an important motivation for participating in the HRSS pilot in primary care.  The majority of patients who participated in this evaluation were happy for their GP practice to share their patient data with the HRSS pilot in primary care."

On the programme's communications efforts:

"Levels of understanding about the detail of the HRSS varied and very few people had a good understanding.  One patient who opted out of the HRSS stated that she would have opted in if she had had clearer, more detailed information about the HRSS pilot in primary care."

Cancer Research UK unites with global research groups (IRCI and EORTC) to fight rare cancers

We missed this press release from Cancer Research UK last week - the only other place we've seen it publicly is on ecancermedicalscience in their Insider News section:


Cancer Research UK will ... join forces with international research groups from the UK, Europe and the US to launch an initiative to boost the development of new treatments for patients with rare cancers. The announcement will be made by Dr Harpal Kumar, chief executive of Cancer Research UK, at the 2011 World Cancer Leaders’ Summit taking place today in Dublin.

The International Rare Cancers Initiative (IRCI) has been established by Cancer Research UK and the National Institute for Health Research Cancer Research Network (NCRN) in the UK, the National Cancer Institute (NCI) in the US, and the European Organisation for Research and Treatment of Cancer (EORTC).

The initiative will design and fund clinical trials of treatments for rare cancers – defined as those which occur in approximately fewer than two cases per 100,000 people. There are limited treatment options for patients suffering with these cancers and there is an urgent need to develop new therapies.

Initially the IRCI will focus on designing clinical trials for five cancer types: salivary gland cancer, small bowel adenocarcinoma, gynaecological sarcoma, ocular melanoma (melanoma of the eye) and penile cancer.

Helene Craddock, 37, a nurse in the intensive care unit at Bristol Children’s Hospital, was diagnosed with cancer of the salivary glands at the age of 19. She said: “Being told you have cancer is a very difficult thing to come to terms with.  You have a lot of questions, which is normal, but having a rare cancer means the answers are not always there. “I am very thankful to say that although I had extensive surgery, and continue to be followed up, I am currently very well.

“There is a huge need to look into these rarer cancers, and I sincerely hope that this new research will lead to improvements in understanding, diagnosing and treating these cancers, and ultimately give us all more hope for our futures.”

The first clinical trial developed as a result of the IRCI, a study for patients with a type of gynaecological cancer called uterine leiomyosarcoma, has recently received approval from both the NCI and Cancer Research UK.  Nine further studies are currently being developed through the initiative. The partner organisations will provide the funding that will enable patients in their countries to take part in the studies.

In addition, it is hoped that studies for other rare cancer types will be developed through the IRCI, including studies in anaplastic thyroid cancer, fibrolamellar hepatoma, thymoma and metastatic/relapsed anal cancer.

Dr Harpal Kumar, chief executive of Cancer Research UK, said: “This initiative is an exciting opportunity for some of the top clinicians in the world to work together to develop and run trials for rare cancers. We hope this will lead to new and more promising treatments for those patients who today have a very limited set of options.

“This is an urgent need. New treatments for rare cancer types are few and far between – these essential clinical trials are the first step in helping these cancer patients. International collaboration is critical to share knowledge and expertise in this area – it will help speed up and improve the design of these trials. We hope this initiative will increase survival from these diseases.”

Professor Matt Seymour, director of the NCRN, said: "Although each rare cancer may affect only a small number of patients, for those people it is critical that we find the best treatments. And combined, rare cancers affect thousands of UK patients every year.

“But research has lagged behind common cancers, partly because rare cancers have not been a priority for drug companies and funders, and partly because it is difficult to organise large-scale trials in diseases only affecting a few patients in any one region.

"Over the past decade, Cancer Research UK and the NCRN have led the world in making cancer research part of routine treatment in every hospital: over 46,000 UK patients took part in NCRN trials last year. We are confident that by bringing together experts from around the worldwe can do ground-breaking research, even in these rare diseases."

Ted Trimble, director of NCI's Center for Global Health, said: “This initiative will allow us to perform trials for cancers so rare that none of us could have managed it on our own.  Working together like this allows us to reduce the cost of trials for each partner organisation, to speed development and conduct of rare cancer clinical trials, and to harness worldwide expertise in these rare conditions.”

Denis Lacombe, EORTC headquarters director, said: “The low numbers of patients with rare tumours brings an urgent need for international cooperation of experts with complementary skills and knowledge to find new ways to treat these diseases.

“This International Rare Cancers Initiative will allow cancer doctors to recruit patients for one large and effective trial, instead of several smaller trials whose results might be inconclusive.

“EORTC embraces this initiative. Rare tumors are a priority at EORTC, which has carried out landmark trials that have changed standard of care for rare cancers such as glioma and sarcoma.

“Patients and public health are at the center of the EORTC mission, and this initiative fits perfectly into the EORTC scientific agenda.”

Notes: 

The following eight rare cancers currently form the core activities of the IRCI.  The names of the lead clinicians for each rare cancer have been listed:

Head and Neck cancer specifically;

Salivary gland cancer 

Leads: Dr Kevin Harrington (UK), Dr Alan Ho (US), Dr Lisa Licitra (EORTC)

Anaplastic thyroid cancer

Leads: Dr Laura Moss (UK), Dr Keith Bible (US), Professor Martin Schlumberger (EORTC)

Small bowel adenocarcinoma

Leads: Dr Richard Wilson (UK), Dr Rob McWilliams (US), Dr Arnaud Roth (EORTC)

Gynaecological sarcoma

Leads: Dr Helen Hatcher (UK) Dr Martee Hensley (US), Professor Jean-Yves Blay (EORTC)

Fibrolamellar hepatocellular carcinoma

Leads: Dr Tim Meyer (UK), Dr Marcio Malogolowkin (US), Dr Michel Ducreux (EORTC)

Penile cancer

Leads: Dr Steve Nicholson (UK), Dr Curtis Pettaway (US), Dr Christine Theodore (EORTC)

Ocular melanoma

Dr Ernie Marshall (UK), Dr Richard Carvajal (US), Professor Poulam Patel (EORTC)

Thymoma

Professor Mike Lind (UK), Professor Frank Detterbeck, Dr Sanjay Popat

Metaplastic/relapsed anal cancer

Dr Rob Glynne-Jones (UK), Dr Al Benson (US), Professor Dirk Arnold

Consultation on building an e-health research infrastructure for cancer

The National Cancer Intelligence Network (NCIN) posted a consultation document on their site last week to coincide with the beginning of the National Cancer Research Institute's annual conference.

It's worth reading this in conjunction with the Department of Health document describing the new Clinical Practice Research Datalink which we blogged about a few days ago as the consultation seeks to co-ordinate its proposals with the infrastructure developments proposed by the CPRD.

In overview (taken from the Executive Summary - these are expanded upon in the main body of the document) the proposals are:

Proposal 1: A safe haven facility to enable research access to potentially identifiable data from the English cancer registration service in a secure, controlled environment. All outputs removed from the safe haven would be checked against anonymity criteria before release.

Proposal 2: A linkage service to allow combination of different datasets for use in research.

Researchers with the appropriate consent could receive data from the cancer registration service to supplement a study dataset. Other researchers could receive access to the de‐identified product of linking one or more existing datasets to cancer registry data.

Proposal 3: A notification service for new cancer diagnoses and other events.

Investigators could register study participants (with their consent) with the cancer registration service and allow them to be regularly informed of new diagnoses and other events.

Proposal 4: A hosting service for study data. This would provide investigators with a secure environment in which to store and analyse their study data together with routinely collected information from the cancer registration service.

Proposal 5: Support for the planning and recruitment of studies.

This would involve mechanisms for estimating trial feasibility and the likely recruitment rates of different centres, and for notifying clinical teams when patients are eligible for a particular study or clinical trial. (Potentially a joint project with the NIHR Cancer Research Network (NCRN) and others).

Proposal 6: A research support service. This would advise users on the availability of data, the requirements for access, and would manage requests and provide access.

Proposal 7: Guidance on guidance on permissions for data access and linkage.  

This would involve providing investigators with guidance on consent wording for using record linkage and notification services. (Potentially joint projects with NRES and NIGB and others).

National Cancer Research Institute's 2011 Conference

In case you are not already following on Twitter (#NCRI2011) or the blog (http://scienceblog.cancerresearchuk.org/) the NCRI conference is in full swing in Liverpool. Unfortunately we're not able to attend this year but we'll be looking out for choice updates to collate and talking to some of our colleagues about the highlights as it progresses.

eCancermedicalscience.com are blogging about it already and quite fulsomely: http://ecancermedicalscience.com/blog.asp?postId=171

Best wishes to all involved.

Continuing Use and Adoption of OpenClinica for Clinical Data Management

Tim Bradford, Bioinformatics and eSciences Manager at the Oxford NIHR Biomedical Research Council, was another proponent of open source, in particular OpenClinica which he noted is now implemented in production environments in 650 instances of which 34 are in the USA and 29 in Europe – he mentioned that 200 regulatory submissions are expected in 2012!

He also mentioned that Oxford do run training in OpenClinica if you’re interested in implementing but lacking the expertise... Tim’s team are aware of the shortcomings of the software and have experience adapting it to meet specific needs – to the extent that “Since adopting the technology 18 months ago it is being used live [by Oxford] in 46 studies across 30 sites and has recruited in excess of 6000 subjects”. He also mentioned that they are using MIRTHConnect  (more open source)

For tissue storage they are using Labvantage Sapphire and to mine clinical data from Cerner Millennium they are using Power Insight.

Application of CancerGrid Technologies to Translational Research

We're nearing the end of our summary of the day's Information Systems workshop courtesy of NOCRI but there's still plenty to cover!

Dr James Brenton, Group Leader at CRUK’sCambridge Research Institute, was one of the day’s pro-caBIG speakers. Wemanaged to jot down some of the nitty-gritty, CancerGrid SQIV integratesclinical and lab data (e.g. TMA slides) using inference rules to create XMLrepresentations of both for the purpose of modeling analytical software andinterfaces. Some of the tech used has been borrowed from Astrogrid who usejava-based tools to manipulate the vast quantities of data necessary fromresearch into the universe. From what we can recall, the CancerGrid andPathgrid softwares will be open and reusable - this is the abstract of Dr.Brenton’s talk:

“CancerGrid is an initiative involvingscientists at the Universities of Oxford and Cambridge, working together to reducethe cost of clinical research, and to increase its value through effective datasharing. It is building upon the success of a four-year project funded by theUK Medical Research Council, to address a wider range of scientific goals, withsupport from Microsoft Research. The CancerGrid team have developed standardsand tools for the automatic production of the systems needed to supportclinical studies and translational research. The vision:

· the researcher createsa model of their study or dataset, based upon standard templates, using asimple study designer tool

· the software artefacts- forms and services - needed to run the study, or interact with the dataset,are then produced automatically from the model

The production process works toimplement exactly the support required through the configuration of familiar,trusted software applications, such as Microsoft Office with SharePoint, or theopen-source eXist XML database - applications that are used throughout the UKNHS, in government, and in industry. Along with a meta-model (or modeltemplate) for clinical studies, based upon the CONSORT statement, and work onthe classification and registration of clinical trials, the project hasproduced an ISO11179-compliant metadata registry, a semantically aware trialsdesign/ management system, and a toolkit for clinical data transformation andintegration. These models and software applications have been tested throughinitial deployment on a small number of clinical studies in Oxford andCambridge. The metadata registry software has been adopted for use within theUS caBIG initiative, and is being evaluated by a number of organisations withinthe UK. Development continues at Oxford, with clinical collaboration inCambridge and London, and technical collaboration with the caBIG team in theUS.”

NIHR / NOCRI Information Systems Workshop - Part 2 - FP7 TRANSFoRm: Translational Medicine and Patient Safety in Europe

Next up, after Mike Denis, in the first session was Prof. Brendan Delaney (Guy's and St Thomas' Charity Chair in Primary Care Research, King's College London) talking about the TRANSFoRM project under FP7 – for the uninitiated, “'Framework programmes' (FPs) have been the main financial tools through which the European Union supports research and development activities covering almost all scientific disciplines.”

The project is looking to develop infrastructure supporting research and diagnostic decision support in primary care – and in the UK is working with GPRD (the primary care data-source). 

Prof. Delaney referred to the well worth reading report from the US Institute of Medicine of the National Academies DigitalInfrastructure for the Learning Health System: The Foundation for ContinuousImprovement in Health and Health Care - Workshop Series Summary 

 

Prof. Delaney’s big statement was that “Research is in crisis!”, his verdict on the recent reports (we will find the link!) on caBIG was that the lesson to be taken is, “Don’t build massive infrastructure projects! They just grow and grow and create wealth for consultants.” Interestingly, other speakers noted that they were using at least one caBIG tool in the development of their own infrastructures.

Prof. Delaney’s work on TRANSForM encompasses a data quality tool, data linkage functionality (browsing, selection, extraction) and semantic mediation – the latter facilitating the transformation of Electronic Health Records (EHRs) into research quality data (EHRs with tabs for CRFs which partially pre-populate and can ultimately be signed-off online).

This last facility is at the heart of the work, using reference ontologies, controlled vocabularies etc. to interpret the EHRs.

The first year’s deliverables (including the privacy framework, security framework and provenance framework – together creating the governance framework) are already available on the website: http://137.73.82.45/Home.html

We’d be interested to know the relative ease of navigation of the regulatory landscape for each of the involved nations.... and will the deliverables form the semantic mediation be published?

This is the abstract for Prof. Delaney’s talk:

“TRANSFoRm is an EU FP7 project that aims to develop and test a digital infrastructure for the 'learning healthcare system'. Specifically we are working to develop capacity within primary care electronic health records to manage research workflow (recruitment and follow up), data collection and record linkage, and to develop diagnostic decision support using a common infrastructure.

NIHR / NOCRI Information Systems Workshop - Part 1

With apologies for the delay in getting this to you, here comes the first of our updates on last Monday's NIHR Office for Clinical Research Infrastructure (NOCRI) Information Systems Workshop!

The workshop was held at Guy's Hospital and the introductory remarks began with a welcome from Professor Simon Lovestone, who is, in addition to being the Director of the Mental Health Biomedical Research Centre at South London and Maudsley & King's College London, Director of Research at King's Health Partners Academic Health Sciences Centre.He was followed by Mark Samuels (MD, NOCRI) and Peter Knight who is now Deputy Director of R&D and Head of Research Information and Intelligence at the Department of Health.

Session 1 - Chair: Prof. Peter Parker, Cancer Theme Lead, NIHR BRC at Guy's and St. Thomas' NHS Foundation Trust & King's College London.

We've blogged twice before about Mike Denis's presentation covering South London and Maudsley NHS Foundation Trust's (SLaM) Clinical Records Interactive Search (CRIS) system - Mike was up first in the first session after the introductory messages and talked on the Vision for Translational Informatics at SLaM.

He talked to two themes in relation to SLaM's creation of a Personal Health Record, the first being the technical aspects (including deep pseudonymisation - meaning that it extends into the free-text within records) and the second being the social aspect that puts the patient in the driving seat of the process but also aims to link Patient Reported Outcomes to research.

An interesting aspect of the technical discussion was the use of intelligent agents to provide automated analysis and predictive analysis - which chimed with Prof. Michael Luck's comments later in the day on the use of computer sicence agents in medical informatics - of which more later.

Mike emphasised the scalability of the approach, the potential to implement it across multiple centres and carry out data linkage inter-organisationally.

Here's the abstract provided for Mike's talk:

“Within SLAM, we have sought to focus on a relatively fine-grain model of clinical informatics, building the Clinical Records Interactive Search (CRIS) system which provides researchers access to full but anonymised data on a large mental health NHS provider covering a 1.2m population catchment area and containing over 180,000 case records. Key areas for resource development which will be outlined include the routine collection of consent for researcher contact, informative data linkage with internal (biological) and external (health and social) data resources, and adding depth to the dataset through natural language processing, shared health records and patient reported outcomes. We believe that these developments, coupled with advances in nested trial designs and electronic health records (EHR) feedback loops will help move the current focus of EHR and 'case register' research in our field from an observational to translational footing.”

Calls for revision to the European Clinical Trials Directive continue to make news

In the Telegraph: EU regulations hindering drug development, say charities

In Pharma Times: Academia and industry push for revisions to Clinical Trials Directive

In eCancerMedicalScience: Medical research organisations urge reform of clinical trials

...to name a few - this is a theme we've been talking about with various organisations in the last year - indeed we've collaborated in the preparation of an introduction to European legislation's impact on clinical research which present for the first time here:

Overview: As with domestic legislation, there is a perception, and evidence to support it, that European legislation has had a negative effect on UK-based clinical research. A number of initiatives have reform in their sights.

The European Clinical Trials Directive and its interpretation in UK law have also contributed to the issues mentioned above in relation to the home market – namely time to initiation of and resource levels required for research: L J Frewer’s editorial in the BMJ (April 2010) Has the European Clinical Trials Directive been a Success? concludes that “Today, five years after implementation, evidence shows that the directive has had a negative effect on translational research.”[1]

This conclusion has been reached by several others in the last few years[2]^{,[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13]}; although there are some dissenting voices[14], they are in the minority. The Academy of Medical Sciences’ report summarises the situation thus: “The broad scope and ‘one size fits all’ approach of the EU Clinical Trials Directive places an unnecessary regulatory burden on clinical trials of both new products and established drugs. The Medicines and Healthcare products Regulatory Agency (MHRA) provides timely authorisation of clinical trials but there are concerns about its interpretation of the EU Directive, the lack of consistent advice to investigators and sponsors, and the approach taken during some clinical trial site inspections. In combination, this situation is hampering clinical trials and discouraging academic and commercial health research sponsors from conducting their studies in the UK.”[15]

The EU-wide Impact on Clinical Research of European Legislation (ICREL) study sought to measure the impact of the Directive on key stakeholders between 2003 and 2007 and reported that non-commercial organisations had been obliged to nearly double their staff performing administrative tasks and pharmacovigilance as a result of the legislation.[16] Furthermore a Cancer Research UK study indicated that the Directive resulted in a doubling of the cost of running non-commercial cancer clinical trials in the UK, in addition to delaying the start of trials.[17]

The transposition of the Directive into UK law and its interpretation (perceived to be more stringent and less pragmatic than that of other EU states) have disadvantaged the UK as the Directive appears to have been implemented inconsistently across the EU: “The UK’s share of global patient recruitment into clinical trials fell from 6% to 2-3% between 2000 and 2006, while the share of the core EU Member States fell less dramatically from 21% to 14% during this period. The UK’s declining position is further exemplified by data that show the time taken to set up for phase III trials in the UK has been above the European average since 2006, and that in 2009, Germany recruited over 2.5 times more patients than the UK into Phase III trials. These data also show that the UK failed to recruit as many patients as France or Spain.”[18]

As with the impact of domestic regulation, the Academy’s respondents felt that there were no discernable improvements to patient safety or to the ethical basis of clinical trials as a result of the Directive.

Again, this appears to have been understood by funders. The MRC express their intent to “ensure that European Union (EU) and UK regulations, such as those set out by the EU Directive on Clinical Trials and NHS Research Governance, and interpretation of these regulations do not present unnecessary barriers to producing evidence about the safety and efficacy of treatments.” [19] The Academy of Medical Sciences’ report also recommends that the Department of Health and Department for Business, Innovation and Skills – supported by the MHRA and other stakeholders should seek to ensure that the Directive is revised to reduce its scope, ensure that its monitoring requirements are appropriate to risk and simplify its reporting requirements.[20]

Additionally, one of the stated aims of the European Clinical Research Infrastructures Network (ECRIN), an EU-funded programme, is to develop a European regulatory framework offering minimal obstacles to medical institutions through requirements adapted to the risk of the individual trial.

[1] L J Frewer, British Medical Journal April 2010: BMJ 2010; 340:c1862 editorial

[2] Meunier F, Dubois N, Negrouk A, Rea LA, Saghatchian M, Tursz T, et al. Throwing a wrench in the works? Lancet Oncol2003;4:717-9

[3] Moulton B. Save European research campaign. BMJ2004;328:286

[4] Hartmann M, Hartmann-Vareilles F. The clinical trials directive: how is it affecting Europe’s noncommercial research? PLoS Clin Trials2006;1:e13

[5] Bosch X. Europe’s restrictive rules are strangling clinical research. Nat Med 2009;11:1260

[6] Singer EA, Druml C. Collateral damage or apocalypse now for European academic research. Intensive Care Med 2005;31:271

[7] Elwyn G, Seagrove A, Thorne K, Cheung WY. Ethics and research governance in a multicentre study: add 150 days to your study protocol. BMJ2005;330:847

[8] Hemminki A, Kellokumpu-Lehtinen PL. Harmful impact of EU clinical trials directive. BMJ2006;332:501-2

[9] Keim B. Tied up in red tape, European trials shut down. Nat Med2007;13:110

[10] Hearn J, Sullivan R. The impact of the “clinical trials” directive on the cost and conduct of non-commercial cancer trials in the UK. Eur J Cancer2007;43:8-13

[11] Pritchard-Jones K. Clinical trials for children with cancer in Europe—still a long way from harmonisation: a report from SIOP Europe. Eur J Cancer2008;44:2106-11

[12] European Science Foundation. Investigator-driven clinical trials. 2008.

[13] Walker, E., Hankins, M. C. and White, S. M. (2009), The effect of the European Clinical Trials Directive on published drug research in anaesthesia. Anaesthesia, 64: 984–989. doi: 10.1111/j.1365-2044.2009.06011

[14] 4. Berendt L, Hakansson C, Bach KF, Dalhoff K, Andreasen PB, Petersen LG, et al. Effect of European Clinical Trials Directive on academic drug trials in Denmark: retrospective study of applications to the Danish Medicines Agency 1993-2006. BMJ2008;336:33-5

[15] The Academy of Medical Sciences: A new pathway for the regulation and governance of health research

[16] Impact on clinical research of European legislation. http://www.efgcp.be/downloads/icrel_docs/Final_report_ICREL.pdf]

[17] Hearn J and Sullivan R (2007) The impact of the “Clinical Trials Directive on the cost and conduct of the non-commercial cancer trials in the UK. European Journal of Cancer 43, 8-13.

[18] The Academy of Medical Sciences: A new pathway for the regulation and governance of health research

[19] From the MRC Strategic Plan 2009-2014, Strategic Aim Two – Regulation, ethics, governance and working with decision-makers: http://www.mrc.ac.uk/About/Strategy/StrategicPlan2009-2014/StrategicAim2/Regulationethicsgovernance/index.htm

[20] The Academy of Medical Sciences: A new pathway for the regulation and governance of health research