a collaborative foundation for new diabetes insights in germany

ACCESSPOINT • VOLUME 5 ISSUE 9 PAGE 45

InsIghts MIXED METHODS REGISTRY CREATION

The authors

Laura Garcia Alvarez, PHD is Senior Consultant, RWE Solutions, IMS [email protected]

Joshua Hiller, MBA is Senior Principal, RWE Solutions, IMS [email protected]

A collaborative foundationfor new diabetes insights in Germany

Researchers conducting analytics and epidemiological studiesusing electronic medical record databases frequently findthemselves short of critical variables. The value from datacollected through a mixed methods registry like DIAREG spansscientific and commercial applications and creates newpotential for exploring relationships between perspectives,actions and outcomes.

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IMS HEALTH REAL-WORLD EVIDENCE SOLUTIONS & HEOR

Researchers conducting analytics and epidemiologicalstudies using electronic medical record (EMR) databasesfrequently find themselves short of critical variables,potentially limiting the breadth of research they canperform. Although widely available EMR databases suchas The Health Improvement Network (THIN), IMS® DiseaseAnalyzer, and the Clinical Practice Research Datalink(CPRD) contain a great deal of longitudinal primary caredata, it is often the case that certain types of informationare missing – either because an EMR field has not beencompleted or because a particular field does not existwithin the database.

In particular, behavioral detail such as reasons for changingtherapy or the physician’s perspective of important clinicalcharacteristics are rarely part of a structured health recordand thus are not contained in mainstream EMR databases.Typically, researchers must then decide whether to sacrificethe breadth of variables captured, and hence limit thestudy scope, or use a purely prospective design andsacrifice time and cost to implement an extendedprospective observational study.

LEVERAGING MIXED METHODS FOR ACOMPREHENSIVE RESOURCETo address these challenges, IMS Health, in partnershipwith AstraZeneca, has developed an innovative registry(DIAREG) of patients with type 2 diabetes mellitus(T2DM). AstraZeneca is committed to demonstrating theefficacy and benefit of its medicines in a real-worldsetting, especially in terms of patient-relevant outcomes.The registry is based on the complementary methods ofretrospective and prospective data collection, therebyovercoming the individual limitations of each, enablingthe creation of a rich data resource for observationalresearch in this area.

IDENTIFYING REQUIREMENTS Work on DIAREG began in 2012. Understanding the keyrequirements for a comprehensive prospective diseaseregistry, IMS® Disease Analyzer in Germany was selectedas the core data backbone, being representative withinput from physicians in general practice as well as

diabetologists,i and validated with a documentedhistory of application in published scientific studies.

Initial analysis of data variables confirmed that DiseaseAnalyzer contained rich information on populationcharacteristics (eg, demographics, medical history) andtreatment patterns (eg, diagnosis, prescriptions, co-medications, co-morbid conditions) in diabetes patients.However, while some data existed for certain diabetes-relevant clinical parameters, such as HbA1c and bodymass index (BMI), this was often recorded less frequentlyor sometimes not at all. Furthermore, other clinicaloutcomes (eg, cardiovascular events, hypoglycemicepisodes, hospitalizations), physician behavior (eg, driversof therapy decision, reasons for dose or treatmentmodification) and patient-reported outcomes (PRO) (eg, general quality of life, disease-specific quality of lifeor treatment satisfaction), were not captured asstructured data within the patient record at all.

As a result of this initial analysis, a set of 27 variables wereidentified for their potential research value if collected, toenhance the available EMR resource.

DIAREG IS BORNThe identified need for an ‘enhanced’ EMR registry tookthe next stage of development down two separate paths– technical and ethical – to achieve an optimal solution.

technical implementationTo facilitate technical implementation of the registry, IMS Health worked closely with the EMR software vendorresponsible for collecting the data underpinning DiseaseAnalyzer. Together, they designed and created thecapability for a retrieve form data capture window (or‘pop up’) to be triggered in the physician office during thepatient visit, based on a set of criteria available within thepatient EMR (eg, diagnosis code, existence of prior anti-diabetic treatment, etc). Every time an eligible patient wasidentified through the trigger, the physician completedan electronic case report form (eCRF) in the ‘pop-up’window to provide the required additional clinical data.

Enhanced insights from a mixed methods approach

patients1,071

DIA

REG

changed therapy22%


i Becher H, Kostev K, Schröder-Bernhardi D. Validity andrepresentativeness of the Disease Analyzer patient database for use inpharmacoepidemiological and pharmacoeconomic studies. Int J ClinPharmacol Ther, 2009; 47: 617-626



Since patient EMR was used as the basis for including orexcluding a patient from the registry, the potential impactof subjective selection was reduced. Consecutive newpatients continued to be triggered for inclusion in theregistry until the physician reached a pre-defined cap, thusproviding a framework for random sample selection. Datacollected from the retrieve form data capture window eCRFis currently being linked back to the EMR using a hash de-id process that removes protected health information(PHI) prior to extraction to the IMS Health database.

In addition to the enhanced clinical data collection, asecond phase of the registry build involved theintroduction of PROs to provide a further layer ofinformation. These are collected via paper-basedquestionnaires handed to patients at the physician sitewhere they are filled in and returned for entry into anelectronic database. An additional hash algorithm hasbeen deployed for one-way linkage of the PRO data tothe EMR and eCRF (Figure 1).

Ethical implementationFrom an ethical perspective, it was essential to ensurethat the registry was developed in accordance with soundobservational research practices. To that end, a ScientificAdvisory Board was created to provide guidance on themethods for site identification, eCRF review, inclusion ofPROs, use of patient informed consent, and submissionsfor ethics approval. The Committee is made up of sixindependent academic researchers and physicians whohave no affiliation with either AstraZeneca or IMS Health.Patients participating in the registry have given informedconsent for inclusion of their information from EMR, aswell as the eCRF and PRO questionnaire. The registryprotocol was reviewed and approved by the EthicsCommittee, Nordrhein, Germany (Ethikkommission derÄrztekammer Nordrhein) under the name of DIAREG.

UNIQUELY GRANULAR OBSERVATIONALRESEARCH As of September 2014, DIAREG has been collecting datafor more than 18 months. The registry currently containseCRF questionnaires, with comprehensive, longitudinaldata variables, for 1,071 diabetes patients, enablinggranular observational research. A subset analysis ofthese patients (n=824) shows that 77% were enrolled byGPs, the remainder being recruited by diabetologists.

Based on data from half of the cohort, average length oftime with T2DM is 12.3 years (median 11 years). Twenty-two percent of patients (n=181/824) in the registry haveexperienced a change to their anti-diabetes therapy atleast once within the last year, mostly by the GP (57%) butalso by diabetologists, who were responsible for 35% oftherapy changes. For 152 patients (84% of the therapymodification population), this took the form of a doseadjustment to their existing therapy, mainly due toinsufficient control of HbA1c (Figure 2). A change of drugwas recorded for 60 patients (33%) for the same reason.Overall, doctors have reported high expectations of HbA1creduction when deciding on a new treatment regimen.

A total of 475 patients (58%) self-monitored their bloodglucose levels, with 30% checking their blood sugar morethan twice a day. Visits to other specialists were recordedfor 43% of 824 patients, the most frequently visited beingophthalmologists (57%) for diagnosis of retinopathies.

Of the 824 patients in the subset, 43 experienced at leastone hypoglycemic event, four of whom requiredhospitalization (Figure 3).

ENABLING EVIDENCE-BASED CONNECTIONS The data captured in DIAREG enables researchers toidentify and explore associations across measures thathave not been collected before in a sustainable andintegrated manner.

Patient characteristics ofinterest programmed into

EMR database to trigger eCRF

EMR and PRO linked to disease-speci�c data atpatient level creating enhanced patient record

Double hash algorithm applied for data anonymization

IMS Disease Analyzer

eCRF pop-up

PRO

Enhanced DiseaseCohort

FIGURE 1: CUSTOMIZEd EMR ANd REGISTRY dATA COHORT

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IMS HEALTH REAL-WORLD EVIDENCE SOLUTIONS & HEOR


By allowing comparison of clinical parameters at apatient level, it provides evidence of associations from areal-world setting that previously could only beidentified anecdotally or through market research. As an example, the capture of BMI and HbA1c

measurements without DIAREG was recorded in 61.9%and 42.3% of the population respectively. With DIAREG,the capture of these critical lab measurements increasesto 83.3% and 77.6% respectively (Figure 4).

Source: Disease registries including Patient Reported Outcomes - IMS® DIAREG

YesNo

Number of patients withat least one dose adjustment

Reason for therapy adjustment

0 20 40 60 80 100 120

16% (n=29)84%

(n=152)

Other

Co-medication

Weight gain

Patient request

Hypoglycemic events

Microvascular complications

Macrovascular complications

Change of substance combination

Insu�cient HbA1c reduction

39

9

13

10

22

16

2

23

112

FIGURE 2: MOST THERAPY AdJUSTMENTS ARE dUE TO POOR HbA1C CONTROL

N= 824 Patients, of which 43 had at least 1 hypoglycemic event as reported in DIAREGSource: Disease registries including Patient Reported Outcomes - IMS® DIAREG

4 or more 3 2 1

Number of patients having a hypoglycemic eventType of

hypoglycemic event

0 2 4 6 8 10 12 14 16

1

1

3

3

4

2

26

712

9

15

1317

Hypoglycemia requiringhospitalization

Hypoglycemia withglucose consumption

Number of events per patient

Hypoglycemiarequiring assistance

Blood sugar <70 mg/dlmeasured by patient

FIGURE 3: PATIENTS EXPERIENCING A HYPOGLYCEMIC EVENT

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Prior to implementation of DIAREG, real-worldinformation on the proportion of patients checking bloodsugar, the reason for modifying treatment, the numberand type of hypoglycemic events, diagnosis for specialistvisits or quantity of lab measurements captured was non-existent. Figure 5 outlines categories of data enhancedthrough the mixed methods approach.

EXTENDED VALUE WITH MULTIPLE APPLICATIONS The value from data collected through a mixed methodsregistry like DIAREG spans scientific and commercialapplications. For researchers, the depth of detail from the

comprehensive patient record allows retrospective analysisusing measures that are not available in other datasets. Forbrand teams, the behavioral information from physiciansand patients, such as reasons for switch and quality of life,creates new potential for exploring relationships betweenperspectives, actions and outcomes.

DIAREG: n=407 patientsSource: Disease registries including Patient Reported Outcomes - IMS® DIAREG

Already in DA Update in DIAREG Missing

57.0%

61.9%

42.3%

29.0%

15.7%

41.0%

14.0%

22.4%

16.7%

0% 10 20 30 40 50 60 70 80 90 100

Blood pressure

Height/Weight

HbA1c

FIGURE 4: dIAREG ENAbLES INCREASEd CAPTURE OF CRITICAL MEASUREMENTS

FIGURE 5: CATEGORIES OF dATA ENHANCEd THROUGH A MIXEd METHOdS APPROACH

Information in IMS® Disease Analyzer

Documented type of diabetes

Therapy duration at the treating physician

Disease-relevant parameters (eg, HbA1c, blood glucose, weight/BMI, blood pressure)

–

–

–

Diabetes-related complications

Referral to hospital

Referral to specialists

Referral to rehabilitation

Patient education

–

–

Information in IMS® DIAREG

Confirmation of type 2 diabetes diagnosis

Start/duration of type 2 diabetes

Complete documentation of all disease-relevant parameters

Frequency and severity of hypoglycemias

Treatment goals (related to symptoms, laboratory parameters and complications)

Reasons for change of therapy and treatment goals associated with the change

Complete documentation of all diabetes-related complications

All stays in hospital with reasons for hospitalization, diagnosis at discharge and hospital days

All specialist consultations with diagnosis

All rehabilitation measures with diagnosis

All educational activities

Frequency of blood glucose self monitoring

Physician's estimate of the patient's therapy adherence

The IMS® DIAREG registry is open to other collaborations.

For further information please [email protected]


a collaborative foundation for new diabetes insights in germany

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