Mapping Outcomes and Registries Used in Current Danish Pharmacoepidemiological Research

Figures & data

Figure 1 Flow diagram illustrating the study selection process. Articles could be excluded due to more than one reason. Thus, the number of articles that meet the specific reasons for exclusion is not mutually exclusive. Adapted from Liberati A, Altman DG, Tetzlaff J et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339(jul21 1):b2700-b2700.⁶⁷

Table 1 Overview of Outcome Categorization and Distribution Across the 210 Included Studies

Categories	n (%)	Subcategories	n (%)	Subtypes	n (%)	Type of Measures
Clinical outcomes	201(96)	Mortality	80(38)	All-cause mortality	60(29)	All-cause mortality; Death by any cause
				Cause-specific mortality	35(17)	Disease/cause-specific mortality; Death by other causes than a specific one
		Diagnosis	138(66)	Diagnosis	131(62)	Diseases/events/hospitalization/hospital admission defined by specific diagnosis (ICD-8/10 codes*)
				Diagnosis/Prescription combination	11(5)	Composite measures defined both by specific diagnosis and by redeemed prescription
				Other	1(<1)	Suicide attempt (ICD-8/10 or contact codes*)
		Surgery and procedures	17(8)	Surgery and procedures	16(8)	Surgeries; Amputations; Blood transfusions; Dialysis, Implantable cardioverter defibrillator therapy; Other procedures
				Other	1(<1)	Organ supportive treatments
		Drug treatment	22(10)	Prescription	17(8)	Redeemed prescriptions of specific medications
				Drug discontinuation/ switch	6(3)	Overall- and cause-specific drug discontinuations, withdrawal, or switch; Add-on treatment
		Disease severity or morbidity	13(6)	Hospitalization	3(1)	All-cause hospitalization
				Severity scale (Disease), Clinical	6(3)	Expanded Disability Status Scale score; Psoriasis Area and Severity Index response score; Minimal joint activity score; Cognitive functioning score
				Other	7(3)	Disease relapse/progression (single measure or composite measure); In-hospital postoperative event (composite of diagnosis, surgery and procedure, and diagnostic measures); Adverse clinical event (composite of new prescription, hospitalization, or surgery); Bradyarrhythmic events (composite of surgery and procedure, and diagnosis); Future atopic dermatitis activity (composite of prescription, contact with private dermatologist and hospital contact)
		Clinical investigations	7(3)	Diagnostic measures	7(3)	Mammographic density; Creatinine kinase-MB level; Coronary angiography; Body Mass Index and overweight; Ultrasound scans; Abnormal electrocardiogram, heart rate, blood pressure, etc. (clinical signs and symptoms of poisoning); Tumor biopsy; Radiological findings; Cerebrospinal fluid cytology and/or flow cytometric immunophenotyping
		Pregnancy and offspring	21(10)	All-cause mortality offspring	5(2)	Stillbirth; Fetal death/abortions (elective or spontaneous); Infant mortality
				Cause-specific mortality offspring	1(<1)	Death due to heart defect in offspring
				Diagnosis offspring	18(9)	Diagnosis in offspring following parental exposure: Birth defects/malformations and other diseases defined by a diagnosis (ICD-8/10 codes*)
				Apgar Score	2(1)	5-min Apgar score
				Preterm birth	5(2)	Preterm birth/delivery
				Small for Gestational Age	5(2)	Low birth weight in relation to gestational age; Fetal growth restriction
				Other	2(1)	Cesarean (elective or acute); Normal or induced birth delivery; Molar and extra uterine pregnancies; Other pregnancy outcomes
Society-related outcomes	9(4)	Work-related	2(1)	Work ability/Productivity/ Connection to labor market	2(1)	Return to work; Workforce detachment (paid sickness leave, early retirement, or any other economic support from the state due to reduced working capability)
		Educational	4(2)	Other	4(2)	Learning disabilities (special educational needs); School performance and cognitive abilities (national academic tests); Student academic performance and/or behavior (exam or teacher-evaluated grade point average); Delayed admission in elementary school
		Criminality	3(1)	Other	3(1)	Prison sentences/incarcerations, and convictions
Healthcare costs and utilization	11(5)	Healthcare costs and utilization	11(5)	Costs	1(<1)	Costs for inpatient and outpatient contacts, primary sector contacts, and medication
				Healthcare utilization	11(5)	All-cause somatic/psychiatric hospital admission; Somatic/psychiatric hospital days; Intensive care unit admissions; Outpatient visits; Activities in connection to hospital contacts; Any readmission/reoperation; Medication use
Patient-reported outcomes, PRO	6(3)	Generic PRO	3(1)	Quality of Life	1(<1)	Visual analogue scale (VAS) of pain, VAS global patient health assessment, Health Assessment Questionnaire-Disability Index
				Other	2(1)	ADHD/Hyperactivity-related behavior (Strength and Difficulties Questionnaire)
		Disease-specific PRO	4(2)	Severity scale (Disease), PRO	3(1)	Disease Activity Score in 28 joints with or without C-reactive protein measurement; Clinical Disease Activity Index score; American College of Rheumatology treatment response score; European League Against Rheumatism treatment response score
				Quality of Life	1(<1)	Dermatology Life Quality Index

Notes: The table present an overview of how outcomes have been categorized into subtypes, into subcategories and further into categories forming the overall hierarchy of outcome types. The number of unique studies using the subtype, subcategory, or category have been stated by frequency (n) and rounded percentage (%) relative to the total number of included studies (N=210). As studies can have investigated more than one outcome subtype/subcategory/category, the numbers and percentages are not mutually exclusive. The last column presents the types of outcomes included under each subtype (mostly stated in an unspecific manner). *In Denmark, diagnoses recorded in registries are coded according to the ICD system with the 8th revision (ICD-8) being used up to 1994, followed by the 10th revision (ICD-10) from 1995¹³.

Abbreviations: ICD, International Classification of Diseases; PRO, patient-reported outcomes.

Table 2 Outcomes Mapped According to Drug Exposure Groups

Studies Included N = 210	Clinical (n = 201)							Society-Related (n = 9)	Healthcare Costs and Utilization (n = 11)	Patient-Reported Outcome (n = 6)
	Mortality (n = 80)	Diagnosis (n = 138)	Surgery and Procedures (n = 17)	Drug Treatment (n = 22)	Disease Severity or Morbidity (n = 13)	Clinical Investigations (n = 7)	Pregnancy and Offspring (n = 21)
Exposure Groups	n	n	n	n	n	n	n	n	n	n
A01: Stomatological preparations (n = 2)	1	2		1
A02: Drugs for acid-related disorders (n = 13)	7	9		1	1		1
A03: Drugs for functional gastrointestinal disorders (n = 2)		1					1
A04: Antiemetics and antinauseants (n = 1)							1
A06: Drugs for constipation (n = 4)		4
A07: Intestinal anti-infectives (n = 7)	1	6		1	1
A09: Digestives, incl. enzymes (n = 3)		3
A10: Drugs used in diabetes (n = 7)	3	6	2				1
A11: Vitamins (n = 1)				1			1			1
A14: Anabolic agents for systemic use (n = 2)	1	1	1	1				1	1
B01: Antithrombotic agents (n = 38)	21	29	3	2			1
B03: Anti-anemic preparations (n = 3)		1		2			2			1
B04: Statins (before 1997)^Citation63 (n = 1)		1
B05: Blood substitutes and perfusion solutions (n = 4)	3	4	1	1	1	1			1
C01: Cardiac therapy (n = 9)	2	6	1		1		1
C02: Antihypertensives (n = 2)		1					1
C03: Diuretics (n = 9)	4	5					1
C05: Vasoprotectives (n = 2)	1	2		1
C07: Beta blocking agents (n = 15)	5	11	2		2		1	1	1
C08: Calcium channel blockers (n = 12)	4	8	1		1		1		1
C09: Agents acting on the Renin-Angiotensin System (n = 12)	4	9						1	1
C10: Lipid modifying agents (n = 15)	7	11	2	1
D01: Antifungals for dermatological use (n = 2)	1	2		1
D05: Antipsoriatics (n = 1)					1
D06: Antibiotics and chemotherapeutics for dermatological use (n = 3)	1	2		1	1
D07: Corticosteroids, dermatological preparations (n = 3)	1	2		1	1
D08: Antiseptics and disinfectants (n = 2)	1	2		1
D10: Anti-acne preparations (n = 2)	1	2		1
D11: Other dermatological preparations (n = 3)		2			1
G01: Gynecological anti-infectives and antiseptics (n = 2)	1	2		1
G02: Other gynecologicals (n = 3)	2	1					1
G03: Sex hormones and modulators of the genital system (n = 10)	3	7				1	2
G04: Urologicals (n = 4)	1	4
H01: Pituitary and hypothalamic hormones and analogues (n = 4)		2					1			1
H02: Corticosteroids for systemic use (n = 7)	1	4	1		1		1
H03: Thyroid therapy (n = 3)	2	1					1
H05: Calcium homeostasis (n = 1)		1		1
J01: Antibacterials for systemic use (n = 16)	3	11		1	1	1	2
J02: Antimycotics for systemic use (n = 3)	1	3		1
J04: Antimycobacterials (n = 3)	1	3		1
J05: Antivirals for systemic use (n = 5)	1	3		1	1		1
J07: Vaccines (n = 12)	3	11		1			2
L01: Antineoplastic agents (n = 10)	4	6
L02: Endocrine therapy (n = 4)	1	2					1
L03: Immunostimulants (n = 3)	1	1			2
L04: Immunosuppressants (n = 23)	5	12	3	7	6	2	1		2	4
M01: Anti-inflammatory and antirheumatic products (n = 18)	6	14	1				1
M02: Topical products for joint and muscular pain (n = 2)		1					1
M03: Muscle relaxants (n = 1)							1
M04: Antigout preparations (n = 2)		2
M05: Drugs for treatment of bone diseases (n = 2)		2		1
N02: Analgesics (n = 11)	5	4	1				2
N03: Antiepileptics (n = 9)	1	4					3	2
N04: Anti-Parkinson drugs (n = 1)							1
N05: Psycholeptics (n = 19)	7	11	2	3		1	1	2	3
N06: Psychoanaleptics (n = 17)	5	9	3	1		1	2	5	3
N07: Other nervous system drugs (n =2)		1					2
P01: Antiprotozoals (n = 4)		3		1
P02: Anthelmintics (n = 3)		2		1
P03: Ectoparasiticides, incl. scabicides, insecticides and repellents (n = 2)		1		1
R01: Nasal preparations (n = 2)					1		1
R02: Throat preparations (n = 2)	1	2		1
R03: Drugs for obstructive airway diseases (n = 9)		3		2	1		3
R05: Cough and cold preparations (n = 4)	1	1			1		1
R06: Antihistamines for systemic use (n = 2)		1					1
S01: Ophthalmologicals (n = 4)	1	3		2			1
S02: Otologicals (n = 2)	1	2		1
S03: Ophthalmological and ontological preparations (n = 2)	1	2		1
Other* (n = 6)	4	4					1

Notes: The table present the number (n) of studies using each outcome-exposure group combination as well as the general number of studies using an exposure group (ATC level 2), outcome category (bold font) and subcategory. The table cells are color-coded according to the number size: dark grey (≥10), medium grey (5–9), and light grey (<5). White cells represent no outcome-exposure group combination identified. As one study can have investigated more than one outcome and more than one exposure group, the numbers are not mutually exclusive. *Drug–drug interaction exposures (ATC level 2: B01 + J01, N05 + C03 or C09, L01 + M01, L04 + M01), Phthalate-containing drug exposures,⁶⁴ or “Torsade de pointes risk drugs”⁶⁵.

Abbreviation: ATC, Anatomical Therapeutic Chemical Classification.

Table 3 Outcomes Mapped According to Data Sources

Studies Included N = 210	Clinical (n = 201)							Society-Related (n = 9)	Healthcare Costs and Utilization (n = 11)	Patient-Reported Outcome (n = 6)
	Mortality (n = 80)	Diagnosis (n = 138)	Surgery and Procedures (n = 17)	Drug Treatment (n = 22)	Disease Severity or Morbidity (n = 13)	Clinical Investigations (n = 7)	Pregnancy and Offspring (n = 21)
Reported Data Source	n	n	n	n	n	n	n	n	n	n
Danish Health Data Authority/Statistics Denmark (n=188)
Danish Central Person Registry (n = 39)	39
Danish Causes of Death Registry (n = 43)	41						2
Danish National Patient Registry (n = 114)		93	10	2	6	1	13		7
Danish National Prescription Registry/ Registry of Medicinal Products Statistics (n = 29)		11		17	2				1
Danish National Health Insurance Service Registry (n=2)					1				1
Danish Psychiatric Central Research Registry (n=20)		9		1		1	9		2
Danish Medical Birth Registry (n = 2)		1					2
Danish in Vitro Fertilization Registry (n = 1)		1
Registry of Legally Induced Abortions (n = 1)							1
Danish Pathology Registry (n = 6)		5				1
Danish Cancer Registry (n = 29)		27					2
Danish Education Registries (n = 3)								3
DREAM Database (n = 2)								2
Danish Central Crime Registry (n = 3)								3
Danish Clinical Quality Program - National Clinical Registries, RKKP (n = 23)
Danish Rheumatology Database, DANBIO (n = 4)				3	1	1			1	3
Danish Dermatology Database, DERMBIO (n = 1)		1		1	1					1
Danish Breast Cancer Group (DBCG) Database (n = 2)		2
Danish Colorectal Cancer Group Database (n = 2)		2
Danish Pancreatic Cancer Database (n = 1)	1
Danish National Acute Leukemia Registry (n = 2)	1	1
Danish National Lymphoma Registry (n = 2)	1				1	1
Danish Registry of Childhood Cancer (n = 1)							1
Danish Heart Registry (n = 1)		1
Danish Vascular Registry (n = 1)		1
Danish Cardiac Arrest Registry (n = 1)		1
Danish Pacemaker and ICD Registry (n = 1)			1
Danish Hip Arthroplasty Registry (n = 1)		1	1
Danish Knee Arthroplasty Registry (n = 1)		1	1
Danish Multiple Sclerosis Treatment Registry (n = 1)					1
Danish Intensive Care Database (n = 1)			1						1
Danish Transfusion Database (n = 2)			2
Other data holders (n = 17)
Danish Twin Registry (n = 1)					1
Danish National Birth Cohort Database (n = 2)										2
Danish Microbiology Database (n = 1)		1					1
Danish Multiple Sclerosis Registry (n = 3)	1			1	2
Western Denmark Heart Registry (n = 2)	2	1	2		1	1			1
Danish Familial Relational Database (n = 1)							1
Danish National Cerebral Palsy Registry (n = 2)							2
Danish Cytogenetic Central Registry (n = 1)							1
Danish Pathology Data Bank (n = 2)		2
Copenhagen Mammography Registry (n = 1)						1
Danish Poison Information Centre (DPIC) Database (n = 1)						1
National Academic Test* (n = 1)								1

Notes: The table present the number of studies using each outcome–registry combination as well as the general number of studies using a registry, outcome category (bold font) and subcategory. The table cells are color-coded according to the number size: dark grey (≥10), medium grey (5–9), and light grey (<5). White cells represent no outcome–registry combination identified. The number of studies is not mutually exclusive as one study can have investigated more than one outcome and used more than one outcome data source. The registries have been categorized according to data holder/permission authority (italic font). *Access to data through the Danish Agency for Information Technology and Learning⁶⁶.

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