Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

Accuracy of multiparametric magnetic resonance imaging to detect significant prostate cancer and index lesion location

Background: Multiparametric magnetic resonance imaging (mpMRI) of the prostate appears to improve prostate cancer detection, but studies comparing mpMRI to histopathology at the time of radical prostatectomy (RP) are lacking. This retrospective study determined the accuracy of mpMRI predicting Gleason score and index lesion location at the time of RP, the current gold standard for diagnosis. Methods: Between April 2013 and April 2016, a database of all men aged more than 40 years who underwent RP after positive transrectal ultrasound biopsy by an experienced urological surgeon was collated at a single regional centre. This was cross‐referenced with a database of all men who had mpMRIs performed at a single centre and reported according to Prostate Imaging Reporting and Data System (PI‐RADS version 1) during this period to generate a sample size of 64 men. A Spearman\u27s rho test was utilized to calculate correlation. Results: Median age of patients was 64 years, the median prostate‐specific antigen at RP was 6.22 ng/mL. mpMRI was positive (≥PI‐RADS 3) in 85.9% of patients who underwent RP. More than 92% of participants had Gleason ≥7 disease. A positive relationship between mpMRI prostate PI‐RADS score and RP cancer volume was demonstrated. An anatomical location correlation calculated in octants was found to be 89.1% accurate. Conclusion: mpMRI accurately detects prostate cancer location and severity when compared with gold standard histopathology at the time of RP. It thus has an important role in planning for future prostate biopsy and cancer treatment

Pharmacovigilance of pregnancy exposures to medicinal products focusing on the risk of orofacial clefts

Background: It is important to obtain robust scientific information on possible safety concerns related to the use of drugs during pregnancy in post-approval settings. Since pregnant women are actively excluded from trials in the clinical development of most products, at the time of the drug entry in the market meaningful human data on the effects of that drug during pregnancy are rarely available. There are approximately 5 million pregnancies in the EU each year, and about 1 in every 10 women of childbearing age is pregnant each year. Insufficient information for management of maternal disease during pregnancy can have teratogenic impact on fetus. Aim and objectives: This reach comprises three studies, in the first study; the goal was to evaluate the maternal use of medicines and the associated risks of cleft lip and/or palate in fetus and to link this to the accuracy and currency of safety information available in prescribing information. The second area of research was aimed at identifying and exploring social and digital media to understand patients’ experiences regarding medicine use during pregnancy. Last, but not least, I contributed to the development of an enhanced pharmacovigilance programme for analysing drug exposure during pregnancy and outcomes in neonate. Method: Firstly, I identified medication-induced risk factors for oral clefts with safety signal detection and safety signal evaluation techniques. Then I assessed the completeness of the safety information for pregnancy exposures in the Summary of Product Characteristics and the Patient Information in the UK and the US. In second study, the content of posts concerning pregnancy and use of medicines in online pregnancy forums was analysed using artificial intelligence in the form of natural language processing and machine learning algorithms. Third, the PRIM (PRegnancy outcomes Intensive Monitoring) system was developed as an enhanced pharmacovigilance data collection method. This was used to improve the quality and content of prospective case reports using sets of targeted checklists, structured follow-up, a rigorous process of data entry and data quality control, and programmed aggregate analysis. Results: For 12 antiepileptic drugs studied there was a statistical disproportionality in individual case safety reports indicative of an increased risk of cleft lip and/or palate. There are inconsistencies between the UK and US safety labels, despite the same evidence being available for assessment. The second study showed that in social media forums many pregnant women with MS shared profound uncertainties and specific concerns about taking medicines during the reproductive period. There was evidence of concealment of information with health care professionals; however, the same evidence was shared with a peer group. The PRIM method of enhanced pharmacovigilance has yielded substantially more information on the safety of fingolimod exposure during pregnancy than has been achieved via the regulatory authority-mandated pregnancy registry. Conclusion: Use of medicines during pregnancy is an important topic for public health. There is a significant need to provide inclusive, unbiased, up to- date information to prescribers and women of childbearing age concerning the use of medicines in pregnancy and postpartum during breastfeeding. Information must be provided in a timely manner by a trusted source and patients should have access to health care professionals with the relevant expertise and knowledge. It is important that the full anonymised data set, along with evidence-based conclusions are made publicly available to inform decision-making

The role of kidney registries in expediting large-scale collection of patient-reported outcome measures for people with chronic kidney disease

In this issue of Clinical Kidney Journal, Van der Willik et al. report findings from a pilot study where they introduced collection of patient-reported outcome measures (PROMs) into routine kidney care in Dutch dialysis centres. It is comparable to a registry-led PROMs initiative in Sweden, published in Clinical Kidney Journal in 2020. Both studies reported low average PROMs response rates with substantial between-centre variation, and both identified suboptimal patient and staff engagement as a key barrier to implementing PROMs in routine care for people with chronic kidney disease (CKD). This suggests that national kidney registries could be well placed to facilitate large-scale collection of PROMs data, but that they may require additional guidance on how to do this successfully. In this editorial, we discuss the current state-of-play of PROMs collection by kidney registries and provide an overview of what is (un)known about the feasibility and effectiveness of PROMs in CKD and other conditions. We anticipate that the fast-growing evidence base on whether, and how, PROMs can be of value in CKD settings will expedite registry-based PROMs collection, which will ultimately lead to more valuable and person-centred services and to enhanced health and well-being of people with CKD

The Neuroscience Information Framework: A Data and Knowledge Environment for Neuroscience

With support from the Institutes and Centers forming the NIH Blueprint for Neuroscience Research, we have designed and implemented a new initiative for integrating access to and use of Web-based neuroscience resources: the Neuroscience Information Framework. The Framework arises from the expressed need of the neuroscience community for neuroinformatic tools and resources to aid scientific inquiry, builds upon prior development of neuroinformatics by the Human Brain Project and others, and directly derives from the Society for Neuroscience’s Neuroscience Database Gateway. Partnered with the Society, its Neuroinformatics Committee, and volunteer consultant-collaborators, our multi-site consortium has developed: (1) a comprehensive, dynamic, inventory of Web-accessible neuroscience resources, (2) an extended and integrated terminology describing resources and contents, and (3) a framework accepting and aiding concept-based queries. Evolving instantiations of the Framework may be viewed at http://nif.nih.gov, http://neurogateway.org, and other sites as they come on line

The NordiNet® International Outcome Study and NovoNet® ANSWER Program®: rationale, design, and methodology of two international pharmacoepidemiological registry-based studies monitoring long-term clinical and safety outcomes of growth hormone therapy (Norditropin®).

OBJECTIVE: Randomized controlled trials have shown that growth hormone (GH) therapy has effects on growth, metabolism, and body composition. GH therapy is prescribed for children with growth failure and adults with GH deficiency. Carefully conducted observational study of GH treatment affords the opportunity to assess long-term treatment outcomes and the clinical factors and variables affecting those outcomes, in patients receiving GH therapy in routine clinical practice. DESIGN: The NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web Enabled Research (ANSWER Program®) are two complementary, non-interventional, observational studies that adhere to current guidelines for pharmacoepidemiological data. PATIENTS: The studies include pediatric and adult patients receiving Norditropin®, as prescribed by their physicians. MEASUREMENTS: The studies gather long-term data on the safety and effectiveness of reallife treatment with the recombinant human GH, Norditropin®. We describe the origins, aims, objectives, and design methodology of the studies, as well as their governance and validity, strengths, and limitations. CONCLUSION: The NordiNet® IOS and ANSWER Program® studies will provide valid insights into the effectiveness and safety of GH treatment across a diverse and large patient population treated in accordance with real-world clinical practice and following the Good Pharmacoepidemiological Practice and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines

The challenges of long-term follow-up data collection in non-commercial, academically-led breast cancer clinical trials: the UK perspective

BACKGROUND: Improved survival rates in early breast cancer and the chronic nature of disease relapse result in a large cohort of patients being available for long-term follow-up (LTFUP) in randomised controlled trials. Whilst of recognised scientific value to assess long-term treatment-related sequelae, the volume of this activity can be challenging for trialists and participating sites, and comes at a considerable cost to research funders and the National Health Service (NHS). A National Cancer Research Institute Breast Clinical Studies Group supported project aimed to characterise UK LTFUP data collection procedures in order to propose improvements. METHODS: Protocols and case report forms for UK non-commercial National Institute for Health Research portfolio early breast cancer randomised controlled trials were reviewed and a questionnaire sent to associated participating NHS sites. Responders were asked to give opinions on issues with follow-up and LTFUP data collection procedures and to suggest potential improvements to practice. Results were used to inform design of a proposed standard LTFUP case report form. RESULTS: Thirty-four trials, involving eight Clinical Trials Units were eligible for inclusion in the review. All trials requested follow-up at least annually up to 5 years, with two-thirds requesting LTFUP after that time point. Information relating to efficacy endpoints was captured for all trials via case report forms; however, precise detail on recording of recurrence, second malignancies and death varied. Separately, questionnaires were returned from 66 NHS sites. Main concerns identified included difficulties in identifying all adverse events from hospital notes, volume of work, bureaucratic data management practices in Clinical Trials Units and perceptions of prioritisation of recruitment over follow-up. CONCLUSION: Variation has existed with respect to detail of LTFUP information requested for UK trials. Improved communication, simplification and standardisation of data and associated collection methods are possible without compromising data requirements for efficient and effective trial reporting. Future use of routinely collected data, captured via electronic means, could transform practices and alleviate resource usage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1745-6215-15-379) contains supplementary material, which is available to authorized users