Building a patient registry one detail at a time

Walt Disney once said, “There is no magic in magic, it’s all in the details.” He was right. In the case of building patient registries, the “magic” depends on getting every detail right, no matter how minor each detail may seem.

The Fourth Edition of the AHRQ “Registries for Evaluating Patient Outcomes: A User’s Guide” has almost 400 pages of detailed information on planning and designing a registry, including issues related to scientific design, ethics, law, data standards, quality assurance and importantly, the recruitment, retention and engagement of patients as partners in the registry.  The success of a registry will depend on the careful work of the registry team to consider how to address each of these issues matched to the specific purpose of the registry and patient population.  

Cerner Enviza is working with the International Gaucher Alliance (IGA) to develop GARDIAN, a global neuronopathic Gaucher disease patient registry. The goal of the registry is to support gaining a better understanding of the natural history of the disease, correlate global phenotypes and genotypes, validate new endpoints or outcomes and generate a data source that can be used for both regulatory evaluation and health technology assessments of emerging drugs for neuronopathic Gaucher disease. 

Designing registries with clinical context 
Gaucher disease is one of a group of rare diseases called lysosomal storage diseases in which the lysosomes of cells lack the ability to break down excess substances and instead store and build up an excess which can cause many different symptoms in patients. Symptoms include tissue and organ damage, easy bruising and fatigue due to anemia and fragile bones.  In neuronopathic Gaucher Disease (Types 2 and 3), symptoms also include neurological complications such as mental deterioration, seizures, and abnormal eye movements. The symptoms are heterogenous across patients where the timing of their appearance and their severity are concerned. Life expectancy in patients with type 2 Gaucher disease is ~2 years whereas the symptoms of type 3 Gaucher Disease typically appear in childhood, but patients can live well in adulthood. The heterogeneity of symptom types, age of onset and severity are some of the specific clinical contexts that needs to be considered in the registry design.

Because many Gaucher disease symptoms rely on subjective assessment, collecting patient reported information in a standardized manner is essential.  But standardizing this information can prove challenging. Patients live all over the world and speak many different languages. Symptoms begin in childhood, requiring data collection from caregivers and patients of various ages.  Neurological complications lead to different levels of understanding and variations in patients’ ability to express their thoughts. Because an existing validated Patient Reported Outcome (PRO) or Observer Reported Outcome (ObsRO) instrument does not exist for neuronopathic Gaucher disease, the registry team needs to design and validate a new PRO and ObsRO. This involves another level of detailed steps that include developing a conceptual framework, defining domains, subdomains and items, and cognitive testing for issues related to literacy levels and translation. 

Every word matters
I recently received a glimpse into the work of some of the members of the registry team to evaluate the results of cognitive testing for the Chinese translation of the PRO being developed for the GARDIAN registry. This process includes qualitative coding and data analysis of verbatim translated transcripts of interviews with patients and caregivers.

 As one can imagine, there are nuances that occur in how caregivers and patients interpret various words. For example, during a team meeting, a question about the fatigue symptom was posed – specifically regarding how tired the patient was on “average” over the last week.   In this scenario, the word “average was interpreted differently. The Oxford English dictionary gives two different definitions: a more mathematical definition (“Estimated by average; i.e. by equally distributing the aggregate inequalities of a series among all the individuals of which the series is composed”) and a more colloquial definition (“Equal to what would be the result of taking an average; medium, ordinary; of the usual or prevalent standard”).  How did the translator translate the word “average” and how did the patients and caregivers understand it?  In this case, the patient and caregiver had trouble understanding the meaning of the question, and the interviewer suggested using the Chinese word translated as “usual” rather than the original word chosen as the translation for “average.” 

This example is just one seemingly tiny detail within the overall process of designing and implementing a patient registry. However, getting that detail and any of thousands of others right impacts the ultimate validity and reliability of the registry. Watching my colleagues at work gave me a new appreciation for the depth of knowledge and experience in each facet that is needed to create a high quality registry and ultimately using that registry for scientific discovery that can help improve patients’ lives.  Attention to every detail is crucial. 

The GARDIAN patient registry team members bring a mix of complementary experience and expertise. Team members who worked on the translation project include: 

1. Kathleen Beusterien, Senior Research Scientist who specializes in Clinical Outcome Assessments (COA). She has preference Real World Evidence (RWE) research expertise and is leading the cognitive interview phase for the PRO and ObsRO, 
2. Graceanne Wayser, Mixed Methods Research Scientist, with a background in patient and physician preference studies, real world qualitative, global research, and PROs
3. Jason Isaacs, Research Analyst, with a background in commercial and regulatory market research. 

To learn more about GARDIAN registry, pleasecontact us.