Doctor shows patient chart

Chances are high that you or someone you know suffers from allergies or asthma. These conditions are the most common—but often overlooked—diseases American’s face, yet developing treatments to address the need of this huge patient population continues to be a struggle.

Almost 18 million adults and more than 6 million children in the US suffer from asthma and allergic diseases, leading to millions of missed work and school days, and almost 2 million visits to the emergency department every year.

The biopharma industry has been working hard to develop new treatments for asthma and allergies that effect how the body reacts to external stimulus, including research into vaccines and immunotherapies. However researchers running these clinical trials face a complex set of challenges that make these projects difficult to deliver.

Pulling the trigger

Many of these patients have multiple allergies and respiratory conditions and will respond to several triggers with the same response – i.e., pollen, pet dander and air pollution all cause them to have trouble breathing. Their symptoms may also be seasonal, or linked to a specific environment or encounter. All of these factors make it difficult to identify and treat patients in a trial.

Most trials in this category focus on patients who are sensitized to only one type of trigger, or to triggers that only occur during a specific season, which can dramatically reduce the potential population of recruits. And because their symptoms are tied to environmental or conditional triggers that may be seasonal, it can be difficult to consistently measure the impact of a treatment on patients throughout the trial lifecycle.

In most cases, researchers have to rely on patient reported outcomes, which come with their own challenges, including what metrics a patient will use to measure their symptoms, how often they will record these symptoms, and in what format. This is further complicated by the fact that many of these trials target pediatric patients who may be too young to accurately record their outcomes. These treatments also often take months before any effect is seen, making compliance difficult in these long studies.

For some biopharma companies, these obstacles are large enough to dissuade them from pursuing asthma and allergy research all together. But that’s a short-sighted view. These diseases represent a huge patient population who are eager for new and better treatments offering significant market potential for those companies that can overcomes these challenges. And although there are no silver bullets, we’ve had success running studies in these research areas, and learned some valuable lessons on how it can be done:

Best practices in study design to improve outcomes

Although a study has to fulfil all requirements form regulatory authorities, it must also take into account the updated guidance form scientific societies. In this regard the major questions to be answered are:

  • Will major outcome be based on nasal only or nasal + ocular symptoms?
  • How will the proportion of symptoms and medication scores be calculated for the total score, the main variable of these trials?
  • What is the minimum important clinical difference definition for sample size estimation?
  • Methods to ensure the allergen exposure: including natural exposure vs. challenge models?
  • For the proof of concept studies, which are the most reliable models and biomarkers? And which is most accurate for use in adaptive and/or parallel trials?

Increasing success in patient recruiting

The question could be, where do the allergic patients come from for a clinical trial? We may find them in allergy clinics or as referral from GP or as response to advertisement or they may be identified in pharmacies by the use of over the counter allergy remedies. Additional recruitment and retention tactics have proven to be successful in this arena:

  • Site recruitment tools (web sites, reference tools).
  • Patient facing materials (education materials, informed consent or assent tools).
  • Outreach and advertising support, taking into account existing differences depending on regions/countries.
  • Subject retention and follow up, compliance strategies, reminders.
  • Site retaining and motivation, study portal, investigator training.
  • Digital subject engagement, pre-enrollment communities, digital outreach in social media.

Study quality

Study quality will need to satisfy all requirements coming from ethical and regulatory principles, and are based on:

  • Proper site identification and patient recruitment
  • Correct data capture, by defining the tools to be used for recording symptoms, diaries, functional testing.
  • Monitoring strategy, based on the principles of data trial execution, through monitoring of data and site data verification.
  • Correct analysis and reporting.

Pediatric populations

Studies in allergic paediatric population have some added difficulties to be solved. When preparing a pediatric development program, pediatric regulations from both the US and the EU must be considered. The requirements are many and there are some differences between the US and EU.

Pediatric data and experience should drive the pediatric development strategy; prior adult experience should not be the sole driver. Between the specific considerations the following should be covered:

  • Design: developmental physiology factors, blood draw volumes, pregnancy and birth control issues, paediatric norms for labs and ECGs, age appropriate formulations, placebo use and concomitant medications accepted.

  • Consent and assent process should include age-appropriate tools designed to explain the study to children in simple terms. Depending upon the age range, more than one set of tools may be needed.

  • Study conduct with patient and family support, facilities for families, tactics to reduce barriers for participation (which may include weekend visits, for example).

  • Specific site considerations: small patient population, staff availability  and motivation.

  • Children have to be involved in the study to ensure acceptance and compliance by the use of age appropriate tools (as web pages, tales, quizzes, etc); stress of the visits should be reduced. 

In summary, allergy clinical trials are challenging, but can be managed efficiently if they are designed and carried out keeping the patient as the center of all activities.


This article was co-authored by Cindy Jackson, Susan Tansey and Adina Knight.

Topics in this blog post: Biopharma, Clinical Trials, Recruiting, Immunology