1136P Feasibility of linking the UK 100,000 genomes project and real-world evidence databases for a melanoma patient population

The cornerstone of life-saving therapy in immune mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody, trialled in two multicentre, randomised-placebo-controlled trials leading to EU and FDA approval, has been available in the UK through a patient-access scheme. Data was collected retrospectively from 2018-2020 for 85 patients receiving caplacizumab, including 4 children, from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial endpoints and historical outcomes in the pre-caplacizumab era. 84/85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalisation (3 days), duration of PEX (7 days) and hospital stay (12 days) was comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalisation was favourable compared with historical outcomes (p<0.05). TTP recurrence occurred in 5/85 patients; all with persistent ADAMTS13 activity <5iu/dL. Of 31 adverse events in 26 patients, 17/31 (55%) were bleeding episodes and 5/31 (16%) were thrombotic events (two unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4/5 deaths caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients receiving caplacizumab outside clinical trials, including paediatric patients. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.

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Multi-Drug Featurization and Deep Learning Improve Patient-Specific Predictions of Adverse Events

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052600 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2600

Author(s):

Ioannis N. Anastopoulos ◽

Chloe K. Herczeg ◽

Kasey N. Davis ◽

Atray C. Dixit

Keyword(s):

Machine Learning ◽

Real World ◽

Variable Number ◽

Patient Specific ◽

Real World Evidence ◽

Genetic Features ◽

The Uk ◽

Therapeutic Compounds ◽

Improve Patient ◽

Reaction Profile

While the clinical approval process is able to filter out medications whose utility does not offset their adverse drug reaction profile in humans, it is not well suited to characterizing lower frequency issues and idiosyncratic multi-drug interactions that can happen in real world diverse patient populations. With a growing abundance of real-world evidence databases containing hundreds of thousands of patient records, it is now feasible to build machine learning models that incorporate individual patient information to provide personalized adverse event predictions. In this study, we build models that integrate patient specific demographic, clinical, and genetic features (when available) with drug structure to predict adverse drug reactions. We develop an extensible graph convolutional approach to be able to integrate molecular effects from the variable number of medications a typical patient may be taking. Our model outperforms standard machine learning methods at the tasks of predicting hospitalization and death in the UK Biobank dataset yielding an R2 of 0.37 and an AUC of 0.90, respectively. We believe our model has potential for evaluating new therapeutic compounds for individualized toxicities in real world diverse populations. It can also be used to prioritize medications when there are multiple options being considered for treatment.

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PMD24 - ASSOCIATION BETWEEN IOL DESIGN AND INCIDENCE OF PCO AND ND:YAG CAPSULOTOMY: A RETROSPECTIVE REAL WORLD EVIDENCE STUDY IN THE UK

Value in Health ◽

10.1016/j.jval.2018.09.1473 ◽

2018 ◽

Vol 21 ◽

pp. S246

Author(s):

M. Dhariwal ◽

D. O'Boyle ◽

C. Bouchet ◽

J. Khan ◽

A. Venerus ◽

...

Keyword(s):

Real World ◽

Real World Evidence ◽

The Uk

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First Real-world Evidence of Meningococcal Group B Vaccine, 4CMenB, Protection Against Meningococcal Group W Disease: Prospective Enhanced National Surveillance, England

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1244 ◽

2020 ◽

Cited By ~ 5

Author(s):

Shamez N Ladhani ◽

Helen Campbell ◽

Nick Andrews ◽

Sydel R Parikh ◽

Joanne White ◽

...

Keyword(s):

Real World ◽

Disease Surveillance ◽

Age Cohorts ◽

Poisson Models ◽

Real World Evidence ◽

Meningococcal Group ◽

Adjusted Incidence Rate ◽

Group B ◽

The Uk ◽

Adjusted Incidence

Abstract Background 4CMenB is a protein-based meningococcal B vaccine, but the vaccine antigens may be present on non–group B meningococci. In September 2015, the UK implemented 4CMenB into the national infant immunization program, alongside an emergency adolescent meningococcal ACWY (MenACWY) program to control a national outbreak of group W (MenW) disease caused by a hypervirulent strain belonging to the ST-11 clonal complex. The adolescent program aimed to provide direct protection for adolescents and indirect protection across the population. Methods Public Health England conducts meningococcal disease surveillance in England. MenW cases confirmed during 4 years before and 4 years after implementation of both vaccines were analyzed. Poisson models were constructed to estimate direct protection against MenW disease offered by the infant 4CMenB program along with the indirect impact of the adolescent MenACWY program in children eligible for 4CMenB but not MenACWY. Results Model estimates showed 69% (adjusted incidence rate ratio [aIRR], .31; 95% CI, .20–.67) and 52% (aIRR, .48; 95% CI, .28–.81) fewer MenW cases than predicted among age-cohorts that were fully- and partly-eligible for 4CMenB, respectively. There were 138 MenW cases in <5-year-olds. 4CMenB directly prevented 98 (95% CI, 34–201) cases, while the MenACWY program indirectly prevented an additional 114 (conservative) to 899 (extreme) cases over 4 years. Disease severity was similar in 4CMenB-immunized and unimmunized children. Conclusions This is the first real-world evidence of direct protection afforded by 4CMenB against MenW:cc11 disease. 4CMenB has the potential to provide some protection against all meningococcal serogroups.

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28478 Risk for depression after diagnosis for vitiligo in dermatology patients: Real-world evidence from a large, urban, Midwestern US, dermatology patient population study

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2021.06.781 ◽

2021 ◽

Vol 85 (3) ◽

pp. AB192

Author(s):

Amber Randolph ◽

Yasmeen Ali ◽

Roopal V. Kundu ◽

Dennis P. West ◽

Beatrice Nardone

Keyword(s):

Population Study ◽

Real World ◽

Patient Population ◽

Real World Evidence ◽

Risk For Depression

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LB1063 Sex differences for incident cancer in patients with rosacea: Real world evidence from a large Midwestern US patient population

Journal of Investigative Dermatology ◽

10.1016/j.jid.2019.06.024 ◽

2019 ◽

Vol 139 (9) ◽

pp. B6

Author(s):

T. Erickson ◽

C. Kosche ◽

E.C. Gwillim ◽

Y. Ali ◽

L.M. Sadowsky ◽

...

Keyword(s):

Sex Differences ◽

Real World ◽

Patient Population ◽

Real World Evidence ◽

Incident Cancer

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Symptoms suggestive of urinary tract infection rates among intermittent urinary catheter users: Real-world evidence research based on a longitudinal patient database in the UK

European Urology ◽

10.1016/s0302-2838(21)00423-1 ◽

2021 ◽

Vol 79 ◽

pp. S42

Author(s):

E. Chartier-Kastler ◽

B. Schurch ◽

C. Chapple ◽

M. Saad

Keyword(s):

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Real World ◽

Urinary Catheter ◽

Infection Rates ◽

Real World Evidence ◽

Patient Database ◽

The Uk

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OP437 Use Of Real-World Evidence In Survival Analysis Adjusting For Treatment Crossover In Cutaneous T-Cell Lymphoma

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462321001045 ◽

2021 ◽

Vol 37 (S1) ◽

pp. 16-16

Author(s):

Neil Hawkins ◽

Rachel Evans ◽

Noemi Muszbek ◽

Trefor Jones ◽

Linda McNamara

Keyword(s):

T Cell ◽

Real World ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Advanced Stage ◽

Synthetic Control ◽

Current Clinical Practice ◽

Cutaneous T Cell Lymphoma ◽

Real World Evidence ◽

The Uk

Real-World Evidence is useful for validating crossover adjustment approaches, particularly when the adjustment is required because a trial does not accurately reflect a health technology assessment (HTA)-relevant population. We use the MAVORIC trial advanced stage mycosis fungoides and Sézary syndrome cutaneous T-cell lymphoma population and data from the Hospital Episodes Statistics to explore and validate crossover adjustment methods.IntroductionThe MAVORIC trial compared mogamulizumab to vorinostat in patients with mycosis fungoides (MF) or Sézary syndrome (SS), subtypes of cutaneous T-cell lymphoma. However, the treatment comparison within MAVORIC may not represent an HTA relevant population from a UK perspective: (i) 72.6 percent of patients randomized to vorinostat switched to mogamulizumab and (ii) vorinostat is not used in current clinical practice in the UK. This study explores methods to adjust treatment effect estimates using different crossover adjustment methods and Real-World Evidence.This medicine is subject to additional monitoring. This will allow quick identification of new safety information. See www.mhra.gov.uk/yellowcard for how to report side effects.MethodsAn advanced stage (stage ≥IIB MF and all SS) population was included. Three methods were considered for treatment crossover adjustment. A synthetic control arm was created using the Hospital Episodes Statistics (HES) dataset. Predicted survival for the MAVORIC control arm, post-crossover adjustment, was compared to the HES to inform the selection of the appropriate methods for adjustment. A direct comparison between mogamulizumab (reweighted to represent the distribution of MF/SS patients in the HES) and the synthetic control was also conducted.ResultsFollowing crossover adjustment of the vorinostat arm, using the inverse probability of censoring weighting method, the overall survival (OS) hazard ratio (HR) estimate for mogamulizumab vs. vorinostat was 0.45 (95% confidence interval (CI): 0.19, 1.07). This adjustment method was considered the most appropriate based on an assessment of assumptions and a comparison of OS between the adjusted vorinostat data and the HES data. The OS HR estimate for reweighted mogamulizumab vs. synthetic control from HES was 0.33 (CI: 0.21, 0.50).ConclusionsReal World Evidence from the HES database can be used to validate crossover adjustment methods and to better reflect current clinical practice in the UK. Results using both methods support each other.

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