OPRI Newsletter
Publications
OPRI has been leading the paradigm shift in real world evidence for the past 12 years, by delivering pragmatic clinical trials, disease registries and database research.
OPRI’s founder, Professor David Price, has been a pioneer in setting new quality standards for database research which are fully adhered to by the research institute.
Publications
A comparison of the real-life clinical effectiveness of the leading licensed ICS/LABA combination inhalers in the treatment for COPD –
Accepted in International Journal of Chronic Obstructive Pulmonary Disease
Advancing the Patient Experience (APEX) in COPD registry: Study design and strengths – Accepted in Journal of the American Board of Family Medicine
Blood Eosinophil Count Predicts Treatment Failure and Hospital Readmission for COPD – Accepted in ERJ Open Research
Development of the Advancing the Patient EXperience (APEX) in COPD registry: a modified Delphi Study – Accepted in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation
Potential severe asthma hidden in UK primary care – JACI In Pract (Severe Asthma)
Evaluating the Real-life Effect of MP-AzeFlu On Asthma Outcomes In Patients With Allergic Rhinitis and Asthma In UK Primary Care – WAO J
Cluster analysis according to biomarker profile differentiates clinical subgroups in the International Severe Asthma Registry (ISAR)
COPD Primary Care: Providing a Clinically Relevant Picture for Clinicians
OPRI
Global Network and Collaborators
The Observational & Pragmatic Research Institute (OPRI) is an independent research organisation distinguished in building and accessing global data sources to drive change in clinical practice around the world. OPRI’s services range from understanding the burden of illness to supporting the delivery of your full marketing product launch plan. OPRI delivers the real-world evidence required to improve patient lives by bridging the gap between academia and the industry.
Global databases we work with:
Global databases we have worked with:
USA
UK
SOUTH KOREA
NETHERLANDS
CANADA
FRANCE
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Research and Development
The Observational & Pragmatic Research Institute Pte Ltd (OPRI) is an independent research institute uniquely placed to deliver advances in research and development in Singapore and globally. OPRI strives to improve the lives of patients through global research and the translation of novel innovations into direct patient impact.
Severe Asthma
In recent years, the treatment options for severe or uncontrolled asthma have been rapidly increasing, especially pertaining to novel biologic therapies. Although biologic therapies may improve asthma symptoms, exacerbation rates, and lung function parameters, they have not been shown to modify the disease process or provide lasting benefits after discontinuation.
The severe asthma working group was formed to focus on 2 key objectives:
Insight into how severe asthma develops in patients and learning about the biological mechanisms that lead to different types of asthma
Informing the development of new therapies for earlier intervention in asthma patients prior to lung function decline
With data from over 9,000 severe asthma patients across 22 countries, the International Severe Asthma Registry is the first of its kind. Rapidly expanding both geographically and in terms of patient numbers, their ambitious goal of becoming a pioneering real-life, adult, severe asthma registry has certainly been realised. Their newest initiative, the CoVID-19 patient response questionnaire, is currently collecting data on severe asthma patients who have or have recovered from this virus. This will help support exciting research into largely unexplored territories, such as the effect of biologics on CoVID-19 patients.
ISAR Protocol
The recently published ISAR protocol details the aims and objectives of the registry, the steps being taken to develop and manage it, as well as the rationale behind each and every decision made. Retrospective and prospective patient data for 95 variables are collected in this registry, including data on clinical features and outcomes, safety, effectiveness, quality of life, and much more.
“ISAR provides a comprehensive overview of severe asthma patients at a global scale,” said Lakmini Bulathsinhala, co-author of the protocol paper. “Going a step beyond simply collecting clinically-relevant data, this registry takes several real-life factors into consideration, and thereby paints a much clearer picture of severe asthma prevalence, management, outcomes, and so on. This will aid effective research into various domains of this disease and has the potential to improve existing care processes as well as develop more effective tools to manage this tricky condition.”
Ongoing research in ISAR - open for collaborators to join!
Funded
CLEAR - Biologic Patterns, ClinicaL OutcomEs And Health Resource Utilization
This project will assess the clinical outcomes and healthcare resource utilization for biologic users who stopped, switched, or continued their initial biologic, as well as for those who do not initiate a biologic although eligible.
PRISM - ImPact of ComoRbidity In Severe AsthMa
This project sets out to illustrate the prevalence of comorbidities upon enrolling into ISAR among a real-life severe asthma cohort, and subsequently to characterise these patients, stratified by therapy (e.g. long-term OCS, biologic use).
LUMINANT - Describe the CLinical OUtcome Before and After Biologic TreatMent by BIologic Class, by INdividuAl Biologic, and by Subgroups of BaseliNe CharacTeristics
The aim of this project is to describe clinical outcomes before and after biologic treatment by biologic class, by individual biologic, and by subgroups of baseline characteristics.
Academic
Hidden Severe Asthma within the COPD population
This project aims to identify and characterise a treatable severe asthma cohort that could respond to biologic treatment within a global population of COPD or ACO.
Identify Predictors (e.g. biomarkers) of Response to Biologics
This project will look at identifying independent predictors of clinical response (no/partial/high) to biologic therapy and evaluate baseline biomarkers that predict a response to biologics.
COPD
Chronic Obstructive Pulmonary Disorder is one of the most common diseases worldwide, however, there are many gaps in our understanding of its progression as well as optimal management techniques. The COPD steering group therefore aims to improve our knowledge of this disease and its patterns and in turn, improve the care provided to affected patients.
Previous Research
Distribution, Temporal Stability and Appropriateness of Therapy of Patients With COPD in the UK in Relation to GOLD 2019
The use of multiple respiratory inhalers requiring different inhalation techniques has an adverse effect on COPD outcomes
New Research
Association between COPD exacerbations and lung function decline during maintenance therapy
In a novel study that aimed to understand the relationship between COPD exacerbations and disease progression, we found that exacerbating patients with high blood eosinophil counts who were not treated with ICS were associated with high rates of lung function decline. This study is the first to draw out the relationship between the eosinophilic COPD phenotype and lung function decline.
“Whether ICS treatment attenuates this lung function decline is something that needs to be examined in future studies,” said Dr. Mohsen Sadatsafavi , co-author of the study. “Regardless, this study sheds light on some of the reasons patients experience greater lung function decline and can aid physicians in identifying those who would benefit from early intervention.”
Adequacy of therapy for people with both COPD and heart failure in the UK: historical cohort study.
Although heart failure is a common comorbidity in COPD patients, guidelines tend to focus on treating one disease or another. This study discovered that only 1/3rd of patients with heart failure and new COPD diagnoses and less than 1/5th of patients with COPD and new heart failure diagnoses were observed to be adequately treated. It also identified specific characteristics associated with inadequate treatment in both groups.
“Poor treatment leads to poor disease outcomes,” said Professor Kostas Kostikas, first author of the study. “While the reasons for inadequate treatment need to be better understood in future research, this study highlights the importance of increasing clinical education about treating multimorbidity in COPD.”
Advancing the Patient Experience in COPD
The Advancing the Patient Experience in COPD (APEX-COPD) registry is the first primary care health system-based registry in the U.S. that tracks COPD patients longitudinally. By combining questionnaires with EMR-extracted data, this registry will provide a comprehensive overview of patient management and outcomes, which will ultimately aid in improving the quality of care provided.
APEX-COPD | Study design and strengths
Most COPD patients in the US are managed in primary care, however, these physicians may not be up-to-date with recent advances in the management of this disease. This often leads to poorer patient outcomes. APEX-COPD is the first primary care COPD registry in the US, and aims to optimize the treatment provided to patients diagnosed with this disease, while also supporting research into various domains such as comparing the effectiveness of various interventions, identifying predictors of response to treatment, and much more.
“APEX-COPD is the first of its kind in the US. One of its key strengths lies in the fact that it links data from medical records with patient perspectives obtained from questionnaires - a vital step in providing a comprehensive, big-picture overview of this disease,” said Chelsea Edwards, a co-author of the study. “Furthermore, APEX-COPD is more than just a location for a data dump - the information collected via this initiative will be analysed and used to provide informed recommendations to both patients and physicians, with the overall aim of improving patient care.”
Ongoing research in APEX-COPD
Advancing the Patient Experience in COPD
The aim of this study is to inform clinicians and other stakeholders of the prevalence and clinical characteristics of non-spirometrically defined COPD in primary care in the US.
Demographic and Clinical Characteristics of COPD Patients in Primary Care in the United States.
The aim of this study acts to inform stakeholders, such as providers, healthcare payors and the scientific community, of the demographic and clinical characteristics of patients with a COPD diagnosis managed in primary care in the U.S.
Inhaler Devices
Despite the existence of efficacious pharmacological agents for asthma, the clinical effectiveness of current inhaled therapies remains poor. The inhaler device steering group works towards characterising the factors which explain the variability in asthma control, focusing on inhaler devices as a key component of new developments to address uncontrolled asthma.
Current Research: MAGNIFY
Maximising Adherence and Gaining New Information For Your COPD
Poor adherence to inhaler devices leads to poorer outcomes - in COPD, this manifests in the form of worsened symptoms, increased risk of lung infections, and increased risk of hospital visits and/or admissions. A common reason for poor adherence in COPD patients is an obvious one: patients simply forget to use their inhalers as prescribed.
This pragmatic, cluster randomized trial is the first of its kind. It will use technology that consists of a sensor attached to the inhaler device and a mobile app. The sensor will record each instance of inhaler use while the app will remind patients when it is time to take their medication.
The overall aim of this novel study is to determine whether this technology can improve the treatment and clinical outcomes of people with COPD.
For more insight into how technology can support the care of patients with respiratory disease, check out Professor David Price’s talk at ERS 2020: The new reality - better asthma care supported by digital health solutions.
Previous Research: iHARP, a database built to answer questions about inhaler technology and poor asthma control:
A multinational observational study identifying primary care patients at risk of overestimation of asthma control:
It was found that patients overestimate their asthma control, with variables such as age, gender, BMI, and others influencing reporting of asthma control. The need for targeted interventions is evident.
Lack of asthma and rhinitis control in general practitioner-managed patients prescribed fixed-dose combination therapy in Australia:
Asthma management in the given cohort was sub-optimal and highlighted unmet needs within asthma care in Australia.
Inhaler Errors in the CRITIKAL Study: Type, Frequency, and Association with Asthma Outcomes:
Various critical inhaler errors were identified, specifically, in DPIs, insufficient respiratory effort was linked to uncontrolled asthma and increased exacerbations. In MDIs, actuation before inhalation was linked with uncontrolled asthma.
Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting:
It was found that even patients using a device with a ‘low error rate’ should have their inhaler technique reviewed if there is evidence of poor asthma control.
Research Highlights
Real-life effectiveness of inhaler device switch from dry powder inhalers to pressurised metered dose inhalers in patients with asthma treated with ICS/LABA.
Poor inhaler technique leads to poor asthma outcomes; and using both DPIs and pMDIs for asthma is associated with worsened inhaler technique. In this novel study, switching to a pMDI for the delivery of ICS/LABA was found to improve asthma control and reduce exacerbations.
“While this study demonstrates the clinical and economic benefits of switching to a pMDI for medication delivery, it must be noted that patient preference, characteristics and other such factors must be considered before the switch is made,” cautioned Professor Chin Kook Rhee, first author of the study. “A major factor in the success observed when switching in this study is likely due to the high levels of guidance received by patients from GPs – previous studies have shown that switching inhaler devices without appropriate instruction and monitoring has led to worse asthma outcomes.”
Does changing inhaler device impact real-life asthma outcomes? clinical and economic evaluation
The switch to pMDIs for ICS/LABA treatment is also a cost-effective one, as this innovative study found. Echoing the results of the previous study, those who switched to pMDIs had significantly fewer severe exacerbations and symptoms compared to those who remained on DPIs – despite the population of this study leaning to the more severe side of the disease.
“The results of this study have the potential to improve the care we provide for asthma patients,” said Dr Hae-Sim Park, first author of the study. “Patients are more likely to persist with their treatment regimen when they begin to use a single inhaler device, which in turn, helps them manage their disease a whole lot better.”
Biomarkers
The identification and validation of biomarkers in drug discovery/development and in disease diagnosis, treatment, prognosis, and prevention play an essential role in therapeutic responses and treatment outcomes. Biomarkers increase the success rate of drug development programmes and thereby accelerate the availability of new therapeutics. The analytical validation phase of biomarker development is characterized by analysis of the performance metrics of the biomarker to ensure that the test is reliable, reproducible and of adequate sensitivity and specificity.
The objective of the group is to undertake studies which:
Develop new knowledge regarding the biomarkers which explain uncontrolled and severe asthma
Inform the development of new biomarker devices and identify new populations for device use
Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations
Blood eosinophil counts (BEC) and fractional exhaled nitric oxide (FeNO) are established biomarkers in asthma and have been associated with the risk of exacerbations. The results of this study showed that the combination of increased BEC and FeNO act as complementary biomarkers in predicting the risk of severe exacerbations in a primary care population.
“Severe asthma exacerbations place a huge burden on patients and affect nearly every facet of their lives,” said Professor David Price, first author of the study. “Risk prediction tools are essential to minimize the chances of a severe exacerbation, as these often land patients in the hospital, and/or increase their steroid use – which comes with a whole host of unwanted and dangerous side effects.”
Association between blood eosinophil count and risk of readmission for patients with asthma: historical cohort study.
Blood eosinophil counts (BEC) are one of the most useful biomarkers in asthma – recent studies have demonstrated their value in predicting exacerbations, characterizing phenotypes, predicting response to treatment, and so on. In this study, we acquired new knowledge by demonstrating a strong association between high BEC counts in the year before an asthma-related hospitalization and the risk of readmission within the following year.
“Identifying patients who are likely to experience repeat exacerbations can help physicians optimize their treatment to mitigate the risk of hospitalization,” said Professor Rupert Jones first author of the study. “The ultimate goal here is to reduce the burden of asthma, and BEC counts go a long way in aiding the achievement of that goal.”
Covid-19
Platform C19
In a new academic initiative, partnering with several Universities, a national CoVID-19 quality improvement programme and unique research database is being launched. The quality improvement programme starts with improving data quality.
Patients are asked to complete a questionnaire on their current health, CoVID-19 symptoms, tests and outcomes which will update the records. Patients will also be pre-consented to be approached for future research.
Current research has not been able to capture the true impact of this disease, as it is confounded by the many people who are self-isolating as well as those who are unable to get tested due to lack of available resources. With the use of questionnaires linked to data from health records, this innovative platform links all the necessary information together and provides a more complete picture of the CoVID-19 pandemic in the UK.
The database will be used to answer a range of epidemiological, therapeutic and shielding research questions utilising current routine data combined from questionnaires and the primary care records. Projects are in the pipeline to identify the at-risk groups and how they compare to existing NHS guidance on shielding; to determine whether existing therapies protect from or augment the damage from Covid-19.”
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