November marks Chronic Obstructive Pulmonary Disease (COPD) awareness month, with this year’s theme being “Living well with COPD-Everybody-Everywhere”. In this blog, we discuss how Real-World Evidence can provide population-based insights that support COPD diagnosis and management, to improve patient outcomes.

What is COPD?

COPD is an umbrella term used when patients have one or more key respiratory conditions: emphysema, which involves damage to the lungs over time, and chronic bronchitis, which involves a long-term cough with a build-up of mucus. Most patients with COPD have a combination of both conditions that contribute to the detrimental impact on patient health.

These conditions make it difficult to breathe and symptoms include cough (with or without mucus), fatigue, respiratory infections, wheezing and shortness of breath (dyspnea) that worsens even with mild activity. These symptoms result in significant morbidity and deterioration in quality of life.

As the condition often develops slowly in older adults (typically after 40 years of age), many people are not aware that they have COPD. An international study in 2015 that included over 30,000 participants in 27 countries, reported an average undiagnosed rate of COPD of 81%.

The primary cause of COPD is tobacco use (9/10 cases), including active smokers and second hand or passive exposure. Other risk factors include indoor and outdoor pollution, occupational dusts and chemicals (ammonia, asbestos, carbon monoxide and frequent lower respiratory infections during childhood.

One of the most concerning aspects of COPD on patient health are exacerbations, generally defined as an acute increase in symptoms beyond normal day-to-day variation. Symptoms of an exacerbation range from increased breathlessness accompanied by cough and sputum production in mild COPD, to life-threatening respiratory failure in severe COPD leading to the need for hospitalisation.

The frequency and severity of exacerbations correspond to the severity of the patient's underlying disease. Infections, particularly bacterial infections, are frequently implicated in exacerbations, with environmental factors such as air pollution also known to act as a trigger. However, the exact cause cannot be determined in about one third of severe cases which makes managing these events even more difficult.

Burden of COPD

COPD is a complex group of chronic lung diseases characterised by airflow obstruction and breathing difficulties. Even though it is recognised as a treatable disease, therapeutic options can only help manage the condition and slow down its progression. COPD is currently the fourth leading cause of death in the world and is projected to be the 3^rd leading cause of death worldwide by 2020.

In 2017, COPD accounted for 5.7% of all deaths with 41.9 deaths per 100 000 individuals. The Global initiative for chronic Obstructive Lung Disease (GOLD) estimates a global prevalence of over 300 million cases of COPD in 2020.

In the United Kingdom alone, the British Lung Foundation estimated the direct economic cost of COPD to the UK National Healthcare Service (NHS) at £1.9 billion each year in 2014. In 2016, the National Institute for Health and Care Excellence (NICE) estimated that 3 million people are living with COPD in the UK, but only 1 million have been formally diagnosed. Studies have estimated that the prevalence of COPD will increase substantially by 2030 in UK nations, with associated rises in both patient deaths and direct healthcare costs.

This clearly demonstrated burden of disease makes COPD a key focus area in any healthcare context but is even more apparent in the environment of the COVID-19 pandemic where individuals with chronic lung diseases are at increased risk of becoming seriously ill.

Diagnosis and treatment of COPD

Receiving a formal COPD diagnosis remains a challenge as it is considered that around 25% of people living with COPD are still undiagnosed. A diagnosis of COPD relies on clinical judgement based on a combination of patient history, physical examination and confirmation of the presence of airflow obstruction using spirometry. Additional tests can also be performed to rule out other problems such as asthma, heart failure or cancer.

Despite the availability of national and international guidelines, evidence suggests that COPD is commonly misdiagnosed in primary care (2 million people were undiagnosed in 2016) and treatment is not always prescribed according to published recommendations. A recent study showed that 1 in 5 patients initiated triple therapy prior to a formal COPD diagnosis. Using Real World Evidence (RWE) could help having a better understanding of the reality of practice in primary care and highlight any areas for potential improvement of COPD management.

There is currently no cure for COPD. The single most important intervention in modifying the course of COPD in patients who smoke is smoking cessation. Studies have proved that smoking cessation slows down the lung function decline and improves survival compared with continued smoking. For one in three smokers with moderate COPD, quitting smoking can prevent progression to severe or very severe COPD in the following three years. Further, smoking cessation reduces mortality and hospital admissions significantly.

Treatments available to patients diagnosed with COPD can relieve symptoms, prevent or minimize exacerbations and complications, and improve exercise performance, but these therapies do help reduce long-term mortality. All treatment must be assessed and implemented according to the specific condition and past history of the patient. To date, the mainstay of chronic management for COPD has been bronchodilator therapy. Options include short- and long-acting β2 agonists (SABA and LABA), and/or short- and long-acting anti-cholinergic (SAMA and LAMA), with or without inhaled corticosteroids (ICS).

The overall aim of ICS therapy is to decrease inflammation and reduce exacerbation rates. Using a combination therapy with both an ICS and a LABA is recommended in patients with severe COPD or a history of frequent exacerbations. Alternatively, LAMAs have also been shown to prevent exacerbations and can be used in combination with LABAs if ICS therapy is not tolerated. When exacerbations persist in severe cases of COPD, patients can ‘step up’ their therapy and move on to a triple therapy involving LABA, LAMA and ICS. However, in patients with severe or very severe COPD and a history of exacerbations, there may be benefit of removing ICS from a triple therapy regimen as long-term complications can arise from prolonged steroid use such as weight gain, osteoporosis and increased pneumonia risk.

Leveraging the UK’s unique health data ecosystem to support COPD Research

Real world data (RWD) can be used to conduct population-based studies in a representative “real world” population. IQVIA Medical Research Data (IMRD) incorporating data from The Health Improvement Network (THIN), a Cegedim Database, includes non-identified electronic patient health record data from over 18 million patients collected from UK GP practices using Vision clinical systems. IQVIA implement a wide variety of privacy-enhancing technologies and safeguards to protect individual privacy while maximising the utility of the data for medical research and treatment analysis. IQVIA Medical Research Data captures coded demographic, administrative data, clinical events, prescriptions, with secondary care and death information. IQVIA Medical Research Data covers several million patient records, approximately 4.5% of the UK population, and provides a valuable source of nationally representative and generalisable data that can be used for robust scientific retrospective cohort studies.

In 2014, a study using IMRD real world data examined changes in the management and outcomes of patients with COPD in UK general practice between 2000 and 2009. This study showed that, while COPD can be underdiagnosed in primary care, the overall prevalence in the UK is increasing, indicating there may be modest improvements in the identification and diagnosis of the disease. This study also revealed that a third of patients with mild or moderate COPD severity were on triple therapy; a high proportion which falls outside of current guideline recommendations.

In 2018, another study leveraging IMRD, with data through to May 2016, evaluated the factors influencing treatment escalation from long-acting muscarinic antagonist (LAMA) monotherapy to triple therapy in patients with COPD. The study’s findings demonstrated again a high use of triple therapy management for many patients, and that COPD exacerbations seemed to be a major driver for treatment escalation. The authors concluded if the GOLD 2017 strategy recommendations were followed more closely by clinicians, there could be a significant reduction in potential overtreatment with ICS steroids, which is potentially both harmful to patients and expensive.

As with many chronic conditions, early diagnosis and appropriate early treatment are key factors in the survival of the patients and a better quality of life. In recent years, an improvement in available treatments and new guidelines have been developed for COPD, the most recent being the GOLD 2020 report.

A clear way to evaluate the impact and compliance with recommendations would be to use more recent Real-World Data to explore current behaviour in primary care. IMRD as a source of population-based insights is updated with the latest available information several times a year, and so can follow the evolving COPD prescribing landscape over time in light of new research and treatment guidance.

For more information on IQVIA Medical Research Data could help you optimise use of real world data, please contact james.philpott@iqvia.com