How to ensure lung safety is an important part of your trial protocol

To avoid risks, sponsors should consider lung function at the beginning of all trial planning

Reza Farienfar – Vice President, Respiratory Solutions at Clario

Lung safety isn’t just a concern for classic respiratory conditions and rare diseases that directly affect the lungs. Many neuromuscular, autoimmune, and inflammatory conditions affect the respiratory system. For example, amyotrophic lateral sclerosis (ALS) causes damage to nerve endings that affect a patient’s ability to breathe as the disease progresses; Crohn’s disease patients often experience severe airway stenosis; and shortness of breath is a leading indicator of pulmonary hypertension.

If sponsors are developing treatments for these types of conditions, lung safety will be a key concern for trial patients. Lung safety can also be an issue if an experimental treatment could potentially impact patients’ respiratory capability. This is especially important to consider if the treatment uses inhalation as a mechanism of delivery, or when the compound can have a systemic effect on lung function.

Yet too often, clinical trials of treatments for non-pulmonary conditions fall short in monitoring respiratory capabilities and lung safety as part of the trial protocol. They may include spirometry or other breathing tests as part of the patient monitoring process but fail to set requirements for how those tests are performed. 

Lung function testing is unique, and it is important to have skilled operators available to administer them. Without that expertise, trial sites increase the chance of capturing inaccurate or misleading lung function results. This could cause investigators to miss common signs of impending distress caused by the disease progression or the treatment itself.

This lack of attention to lung function can lead to unnecessary safety risks and can cause sponsors to overlook valuable endpoint data – the ability to breathe – as a measure of safety and treatment effect. Ensuring accuracy is particularly important if the treatment relies on respiratory parameters as endpoints.

Lung safety in clinical research

To avoid these risks, sponsors should consider lung function at the outset of all trial planning. When planning trials where lung function matters, we encourage sponsors to consider the following:

1. Choose collaborating partners with specific lung function experience. If respiratory concerns are relevant to the disease and/or treatment, sponsors should look for contributing organisations with experience managing trials where lung safety is an issue. Working with experts ensures sponsors get the guidance they need to select the best protocols, inclusion/exclusion criteria, and endpoint data points to track lung function as part of the trial process.
   
   
2. Make lung function part of inclusion/exclusion criteria and protocol design decision making. Considering lung function during these planning steps helps sponsors ask the right questions up front to uncover hidden risks before the trial begins. This can help them avoid costly protocol amendments, and to ensure the best possible population of patients are targeted for the trial.
   
   
3. Make pulmonology part of the site selection criteria. If the patient population is at risk of lung function issues, sponsors should require sites to have a pulmonologist and pulmonary function lab (PFT) expertise on site. Making respiratory expertise part of the selection criteria can help sponsors avoid choosing sites that cannot meet trial requirements.
   
   
4. Plan to pay for that expertise. Sponsors cannot assume that just because a site has a PFT lab on the premises that it – and its staff – will be at their disposal. If sponsors want patients to be seen by a lung specialist, or expect to use specialized respiratory equipment, it must be considered during the vendor/CRO selection process. This is an often-overlooked element of trial planning that can leave sponsors frustrated and cause disruption at trial sites who don’t have the resources to address these treatment and monitoring requirements. 
   
   Paying for respiratory services will cost more up front, but if it helps to prevent adverse events, monitor disease progression, and maintain high data quality with low variability produced at sites, it will more than pay for itself.
   
   
5. Make respiratory issues part of the training process. Teaching site staff and clinical research associates (CRAs) about lung function risks, how to monitor them, and why they are relevant creates a safer environment for all patients and ensures consistent data collection throughout the trial.

These added steps to address lung safety require more upfront thought and planning. But in the long run they result in better, safer, and more robust trials that can provide sponsors with compelling trial data that will give them an edge in an increasingly crowded marketplace.