Understanding Why Creative Solutions Are Necessary
With last month’s celebration of Rare Disease Month and specifically, Rare Disease Day, awareness of the research challenges faced by patients and pharma companies are especially high during this season.
Veristat focuses on rare and ultra-rare disease clinical trials and related regulatory submissions throughout the year, of course, and 30% of our total work is in this specific area. To date, we have worked on hundreds of clinical projects and prepared more than 25 regulatory submissions for novel rare disease therapies.
With so much knowledge, experience and expertise, it’s no surprise we’ve developed creative approaches to overcoming the challenges presented with designing and implementing rare disease studies.
Here in Data Management, we’re keenly aware of the complexities in creating a data acquisition strategy that will best work with the specialized protocols often designed for smaller patient populations. So, we’ve come up with some special considerations for building a database for a rare disease trial.
Why Flexibility is Critical for Rare Disease Trials
A successful data management strategy must assume that there will be many protocol amendments, challenges in defining Adverse Events (AEs) and an overwhelming amount of extraneous lab data. It is critical to understand why these challenges exist prior to database design.
Given how hard it is to recruit patients with rare diseases, I’ve seen a high rate of protocol amendments throughout these trials specific to:
- Changes to Inclusion/Exclusion Criteria - to allow inclusion to a subject who may have previously been excluded
- Modification of Study Design or Study Assessments - as patient disease progresses, changes to their treatment plans or ability to participate in some elements of the trial may need to be adjusted. Similarly, sponsors could modify study protocol to allow for additional or earlier interim analysis to have visibility into efficacy or safety.
Another challenge that complicates the data is the poor patient quality of life. It may not be clear if adverse event symptoms result from the disease or study drug. Proactive attention should be given when designing the study and the database to consider how Adverse Events are defined and captured – for example, we don’t recommend capturing every sign and symptom, rather, would recommend just entering the single diagnosis (or none at all if the signs and symptoms are a result of the underlying disease being studied).
Lastly, a clear understanding of what lab data is entered into the database requires careful attention. If patients are undergoing transplant surgery or being treated for autoimmune diseases, for example, they may be hospitalized for long durations, further complicating the data. In this case, we want to work with the sponsor upfront to be clear on data collection frequency – labs and vitals may be taken daily (if not hourly) when patients are hospitalized, and we want to clarify what data make it into our system. This keeps us from overloading the database with unnecessary data that will be costly and time intensive to clean later on.
How to be Flexible In Database Design
We proactively prepare for such anticipated protocol amendments and specialized considerations of data by building the clinical trial database with much more flexibility than we traditionally would. One such strategy is to allow more free text fields instead of finite code lists. An oversimplified example is to make the protocol number field a free text field instead of a picklist. Therefore, the picklist field doesn’t need to be updated with every protocol amendment, which might impact the structure of the database and cause downstream delays.
Every rare disease trial is truly unique, therefore requiring specific proactive consideration of how and where to apply flexibility.
Why This All Matters
Over the years, we’ve discovered that rare diseases are not always as rare as we may think. At Veristat, we’ve worked on trials related to auto-immune diseases, blood disorders, cardiovascular diseases, central nervous system disorders, endocrine disorders, gastro-intestinal disorders, genetic disorders, infectious diseases and rare cancers.
Fortunately, patients with rare diseases and their families are among the most involved and proactive patient populations in the world. They participate in trial design and help recruit other patients as well as build registries. Most of all, they want rare disease therapies that work, and they are encouraging sponsors to take their research to the international level. At Veristat, we think this is a promising approach.
Therefore, when it comes to staying flexible during the data management of rare disease trials, we are up for anything and everything that will improve the quality of the clinical trial data!
About the Author:
Associate Director of Data Management, Veristat
Kathleen has been with Veristat for over 3 years and currently leads the day to day operations of the data management team. She works closely with clients to determine the most effective and efficient data management strategies to implement for each unique clinical trial.
Learn more about Veristat's Rare Disease Clinical Trial and Regulatory Submission experience. Or, read some of our latest success stories.