Multi-database networkstudies in a Nordic context · Morten Andersen 2017-06-01 1 Morten Andersen Department of Drug Design and Pharmacology Multi-database networkstudies in a Nordic

MortenAndersen 2017-06-01

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Morten Andersen

Department of Drug Designand Pharmacology

Multi-database network studies in a Nordic context

Conflicts of interest

• Participate(d) in research projects funded by AstraZeneca, H. Lundbeck & Mertz, Novartis, Nycomed, Merck Sharp & Dohme and Pfizer, with grants paid to the institutions where I have beenemployed

• Personally receive(d) fees from Medicademy, the Danish Pharmaceutical Industry Association for teaching at pharmacoepidemiology courses

• Professorship in pharmacovigilance funded by the Novo Nordisk Foundation

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Combining observational data from multiple countries is attractive

Possibilities/advantages

• Increased power• Rare exposures• Rare outcomes• Subgroups• Validate results across

countries• Learn from between-

country differences

Challenges

• Permissions• Logistics• Analysis

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The study will utilise high quality prescription databases and other national data sources, integrated at European level with advanced methods of harmonising data

CAncer Risk and INsulin analoGues

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CARING Study declaration of interests

The research leading to the results of this study has received funding from the European Community’s Seventh Framework Programme (FP-7) under grant agreement number 282526, the CARING project. The funding source had no role in study design, data collection, data analysis, data interpretation or writing of the presentation.

Research questions in CARING WP3

• To develop a common data model allowing the integration of information from differently structured databases

• To evaluate meta-analysis of aggregate patient data (APD) as compared with individual patient data (IPD) for the analysis of the association between exposure to different types of insulin and risk of cancer

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Data sources

STUDY PERIOD1989 2013

CARING

CPRD (UK)

Finland

Denmark

Norway

Sweden

• National registers from Denmark, Norway and Sweden and the UK CPRD

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Prescribed Drug Register

Drug, dispensing form, strengthPackage, amount, dose textATC code, DDDsPatient and prescriber information

Hospital Electronic Records

Clinical informationMeasurements and lab dataInpatient medical treatmentDischarge summary

LISA

Education, income, employmentCountry of birthPlace of residence

Quality registers

Specific diagnoses, treatmentAge at onset of diseaseClinical and lab dataDisease severityRisk/prognosis assessmentBMI, smoking

Medical Birth Register

Identity of mother and childSocial factors, smoking, snuffMaternal, pregnancy, delivery and infant clinical information

Total Population Register

Dates of Immigration, emigration, death

Cause of Death Register

Date of deathCauses of deathInjury, poisoning, intent

Cancer Register

Date of cancer diagnosisType of malignancy, histologyTNM staging

Primary Care Electronic Records

Date of contact, diagnosesClinical and lab dataWeight, blood pressureBMI, smoking, alcoholPrescribed medicine

Patient Register

Inpatient admission and discharge datesOutpatient contact dateHospital, clinic, countyDiagnoses, procedure codes

Multi-Generation Register

Identity of relatives

Swedish health registers

Personal identity number

Laboratory data

Date, measurement, value, unit

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Data sources

STUDY PERIOD1989 2013

CARING

CPRD (UK)

Finland

Denmark

Norway

Sweden

• Nordic healthcare registers are relatively similar in content and structure, easily standardised

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Data management in an epidemiologicalstudy

DATA IMPORT AND CLEANING

GENERATION OF ANALYSIS DATASET

STATISTICAL ANALYSIS

SIMPLIFIED:

RAW DATA CLEANED DATA ANALYSIS DATASET

RESULTS

DATABASE SOFTWARE

STATISTICAL SOFTWARE

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CARING study data challenge

Five complex databases with different medical classification systems – like five different studies

ICD7ICD8ICD9ICD10ICDO3NCSPATC

DK

FI

NO

SE

UK READCPRD PC

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CARING study data solution

Alternative: decide on a common data model

ICD7ICD8ICD9ICD10ICDO3NCSPATC

DK

FI

NO

SE

UK READCPRD PC

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Overview of CDM data flow in the CARING project

DK NO SE UKFI

Nordic Data Model

CARING Common Data Model

Analysis datasets

Concept Dictionary

Statistics Denmark

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Objective: No diagnoses and drugs hardcoded in statistical programs, all definitions contained in a database

CARING CDM – Concept Dictionaryand Breast Cancer Concept


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Multi-database analytic approaches

• Individual patient data meta-analysis• Pooled data in one place necessary• Adjustment for confounders common to all databases

• Aggregate data meta-analysis• Distributed analysis in separate databases possible• Adjustment for database-specific confounders (country-

optimized)

• Method paper: Preliminary results from 3 countries

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Glargine versus human insulinGlargine versus human insulin(preliminary analysis)


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Detemir versus human insulin(preliminary analysis)

Other insulin versus human insulin – differentadjustment models (preliminary analysis)

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Pooled individual patient analysis ormeta-analysis on aggregate data?

Common confoundercovariates (+)

(-)

Power in each dataset (+)

(-)

Favors aggregate level Meta-analysis

Favors individual patient analysis

Nordic studies of SSRIs in pregnancy

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Association of SSRI/venlafaxine and cardiovascular birth defects(Selmer 2016 Pharmacoepidemiol Drug Saf)

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• Fixed effects meta-analysis and individual-basedanalyses of a pooled dataset gave similar results

• Country-optimized adjustment attenuated the estimates more than adjustment for commoncovariates only

• When data are sparse, pooled data on the individuallevel are needed for adjusted analyses

Association of SSRI/venlafaxine and cardiovascular birth defects(Selmer 2016 Pharmacoepidemiol Drug Saf)

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Multi-database networks in pharmacoepidemiology

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BIG(HEALTHCARE)

DATA

A common Nordic pharmacoepidemiology database for the future?

Approaches

• Distributed database network + analysis programs

• Distributed network + secure servers and commonanalysis platforms for individual-based data

• Common Nordic database, all in one place

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A common Nordic pharmacoepidemiology database for the future?

All approaches involve

• Collaboration on a common data model

• A common platform for data management and analysis

• A coordinated process for data access (legal, ethical, mutual agreements)

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Opportunities in safety and effectivenessresearch using Nordic healthcare databases

• Pharmacovigilance: Systematic proactive surveillance, signal detection and risk evaluation using healthcaredatabases

• Comparative safety and effectiveness: Observationalstudies and pragmatic clinical trials linked to healthcare databases (including electronic healthrecords and quality registers)

• Developments in personalised/precision medicinelinking healthcare data to biobanks

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References

• Furu K, Wettermark B, Andersen M, Martikainen JE, Almarsdottir AB, Sørensen HT. The Nordic Countries as a cohort for pharmacoepidemiological research. Basic Clin PharmacolToxicol, 2010;106(2):86-94.

• Wettermark B, Zoega H, Furu K, Korhonen M, Nörgaard M, Sörensen HT, Almarsdottir AB, Andersen M, Andersson K, Bergman U, Englund C, Hallas J, Heli-Salmivaara A, Hoffmann M, Kieler H, Martikainen J, Mortensen M, Petzold M, Ringbäck Weitoft G, Skurtveit S, Wallach Kildemoes H, for the Nordic Pharmacoepidemiological Network (NorPEN). The Nordic prescription registries as a resource for pharmacoepidemio-logical research – A systematic literature review. Pharmacoepidemiol Drug Saf 2013;22(7):691-9.

• Bazelier MT, Eriksson I, de Vries F, Schmidt MK, Raitanen J, Haukka J, Starup-Linde J, De Bruin ML, Andersen M. Data management and data analysis techniques in pharmacoepidemiological studies using a pre-planned multi-database approach: a systematic literature review (review article). Pharmacoepidemiol Drug Saf, 2015 Sep;24(9):897-905. doi: 10.1002/pds.3828. Epub 2015 Jul 14.

• Selmer R. Haglund B, Furu K, Andersen M, Nørgaard M,Zoëga H, Kieler, H. Individual-based versus aggregate meta-analysis in multi-database studies of pregnancy outcomes: The Nordic example of selective serotonin reuptake inhibitors and venlafaxine in pregnancy. Pharmacoepidemiol Drug Saf. 2016 May 19. doi: 10.1002/pds.4033.

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Documents

Multi-database networkstudies in a Nordic context · Morten Andersen 2017-06-01 1 Morten Andersen Department of Drug Design and Pharmacology Multi-database networkstudies in a Nordic