Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective

Figures & data

Table 1. Administrative information on eight Swedish Health Care Quality Registries included in the survey.

Registry (abbreviation, certification level)^a	Target patient population	Subregistries, subprojects	Website	Website in English
Swedish Multiple Sclerosis Registry (SMSreg, 2)	Multiple sclerosis	Under the heading of NEUROreg, there are 7 subregistries besides SMSreg: Parkinson's disease, narcolepsy, myasthenia gravis, inflammatory polyneuropathy, epilepsy, severe vascular headache, motor neuron disease	www.neuroreg.se	http://www.neuroreg.se/en.html
National Prostate Cancer Registry of Sweden (NPCR, 1)	Prostate cancer	Five-year follow-up study	www.npcr.se	www.npcr.se/in English
Riksstroke (Riksstroke, 1)	Stroke and TIA	Childhood stroke module launched 1 January 2016	www.riksstroke.org/swe/	http://www.riksstroke.org/eng/
Swedish Macula Registry (MACULAREG, 2)	Diseases of the macula of the eye and associated complications, age-related wet macular degeneration, myopia, chronic retinal central serosa, inflammation, angioid streaks, trauma, idiopathic, macular telangiectasia, other.	Thrombosis registry (CRVO = central retinal vein occlusion; BRVO = branch retinal vein occlusion; HRVO = hemi retinal vein occlusion)	http://rcsyd.se/sm/	Not established in English
Swedish National Diabetes Registry (NDR, 1)	Diabetes mellitus (types 1 and 2)	SWEDIABKIDS (<18 y)	www.ndr.nu	https://www.ndr.nu/#/english
Swedish Rheumatology Quality Registry (SRQ, 1)	Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis	Myositis	www.srq.nu	http://srq.nu/en/
SWEDEHEART—The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART, 1)	Acute coronary syndromes, myocardial infarction, coronary angiography, percutaneous coronary intervention, coronary by-pass surgery, cardiothoracic surgery, percutaneous valve intervention (TAVI/mitral), cardiogenetic disorder	RIKS-HIA: Coronary care, acute coronary syndromes, myocardial infarction; SEPHIA: Secondary prevention after myocardial infarction; SCAAR: Coronary angiography, percutaneous coronary intervention; Swedish heart surgery registry (HKIR): Cardiothoracic surgery, coronary by-pass surgery; Percutaneous Valve Registry (PVR): percutaneous valve intervention (TAVI/mitral), cardiogenetic disorders	http://www.ucr.uu.se/swedeheart/	http://www.ucr.uu.se/swedeheart/index.php/dokument-sh/arsrapporter Information on SWEDEHEART is available in: Jernberg T Heart. 2010 Oct;96(20):1617-21 (PMID: 20801780), Lagerqvist B Engl J Med. 2014 Sep 18;371(12):1111-20/web appendix (PMID: 25176395)

^a Certification level is a rating given to each registry and represents the level of development the registry has reached in terms of analyses, inclusion of relevant indicators, coordination with health services, use in research, data quality and reporting, coverage rate, technical solutions/tools, etc. There are four levels in total: 1 (highest), 2, 3, and the candidate level (lowest) (http://kvalitetsregister.se/englishpages/findaregistry/certificationlevels.2029.html).

Table 2. Information on inclusions and coverage of quality of care registries (autumn 2015).

Registry		SMSreg	NPCR	Riksstroke	MACULAREG	NDR	SRQ	SWEDEHEART
2. 1	Total cumulative no. of patients included:	16,800	150,000	440,000	21,439	500,000	64,947	>1.5 million
2. 2	No. of patients included per year (approx. mean last 3 years):	2,800	10,000	24,000	3,700	384,124 (no. of updates per 2015)	9,800	80,000 Subregistries^a: RIKS-HIA: 44,089 care episodes SEPHIA: 60,000 patients since 2005, follow-up data for 6,532 patients SCAAR: 39,965 coronary angiographies HKIR: Number of registered operations/procedures =5,613 PVR: 425 TAVI procedures
2. 3	No. of participating centers/clinics out of eligible units:	60	54	72	38	1,260 (= health care centers); 90 (= hospitals)	60	73
2. 4	No. of eligible centers/clinics:^b	60	54	72	41^c	–	60	73
2. 5	Proportion of eligible patients (=coverage) included in the registry (%):	83	98	91	80	95	82	100% for the interventional registries, >90% of all cases of myocardial infarction
2.6	How is coverage calculated (defined by each registry)?	Patients in MSreg compared to national prevalence	Compared to Cancer Registry	Proportion of patients with 1st stroke in Riksstroke compared to patients with 1st stroke diagnosis in Patient Registry	Comparison with PAR (national Patient Registry)	Comparison between the NDR and the nationwide Prescribed Drug Registry	Comparison of data from SRQ and national Patient Registry	Cases in registry versus cases in public mandatory registries (PAR)

^a Data from 2014; source: http://www.ucr.uu.se/swedeheart/index.php/dokument-sh/arsrapporter/doc_download/392-swedeheart-arsrapport-2014-english-engelsk.

^b Hospital clinics, hospital outpatient clinics, primary health care centers.

^c Data from 2014 annual report.

Table 3. Patient population and controls.

3.	Data content/elements:	Yes (n)	No (n)	Yes—which registry	No—which registry
3. 1	Are patients participating in ongoing RCTs included in the registry? (Y/N)	4	3	SMSreg, NPCR, SRQ, SWEDEHEART	Riksstroke, MACULAREG, NDR
3. 2	Are RRCTs possible to perform within your registry? (Y/N)	6	1	SMSreg, NPCR, Riksstroke, MACULAREG, SRQ, SWEDEHEART	NDR: in future, yes
3. 3	Is it possible to create a control group? (Y/N)	6	1	NPCR, Riksstroke, MACULAREG, NDR, SRQ, SWEDEHEART	SMSreg
3. 4	Are patients from other countries included in the registry? (Y/N)	2	5	SWEDEHEART: ‘Iceland directly, Norway in a parallel SCAAR registry’, NDR: ‘Iceland—SWEDIABKIDS’	SMSreg, NPCR, Riksstroke, MACULAREG, SRQ
3. 5	Demographic limitations, e.g. age group, geographical? (Y/N)	1	6	NDR	SMSreg, NPCR, MACULAREG, Riksstroke, SRQ, SWEDEHEART
	If Yes, please specify			>18 y^a	SWEDEHEART–SEPHIA: Age limit of <75 years

^a In NDR patients, >18 y is registered; if <18 y, SWEDIABKIDS is used.

Table 4. Data recorded in the Quality of Care Registries.

		Yes (n)	No (n)	Yes—which registry	No—which registry
1. Data elements registered at inclusion in registry
1. 1	Age (Y/N)	7	0	All
1. 2	BMI (Y/N)	2	5	NDR, SWEDEHEART	SMSreg, NPCR, Riksstroke, MACULAREG, SRQ
1. 3	Sex (Y/N)	7	0	All
1. 4	Diagnosis (Y/N)	7	0	All
1. 5	Comorbidities (Y/N)	4	3	Riksstroke, NDR, SRQ, SWEDEHEART	SMSreg, NPCR, MACULAREG
1. 6	What terminology for coding of diagnosis and comorbidity is used?
	ICD-10	6	1	SMSreg, NPCR, Riksstroke, NDR, SRQ, SWEDEHEART	MACULAREG
	Other	2	5	MACULAREG, SWEDEHEART	SMSreg, NPCR, Riksstroke, NDR, SRQ
	Free text	0	7		All
1. 7	Time point for disease onset (Y/N)	7	0	All
1. 8	Disease activity/state (Y/N)	7	0	All
	If Yes, please specify used measurement	Riksstroke: Level of consciousness, functional dependence at onset; functioning at 3 and 12 months; SRQ: DAS28, HAQ, BASDAI, EQ-5D; SWEDEHEART: Shock, Killip class, severity and distribution, duration of symptoms
2. Medication—drug of interest
2. 1	Is indication for treatment with drug of interest recorded in the registry? (Y/N)	7	0	All
2. 2	If yes, what terminology for coding of indication is used?	–	–	–	–
2. 3	What elements concerning medication are recorded?
	Product (Y/N)	5	2	SMSreg, NPCR, MACULAREG, NDR, SRQ	Riksstroke, SWEDEHEART
	Substance (Y/N)	6	1	SMSreg, NPCR, Riksstroke, NDR, SRQ, SWEDEHEART	MACULAREG
	ATC code (Y/N)	2	5	NDR, SRQ	SMSreg, NPCR, Riksstroke, MACULAREG, SWEDEHEART
	Dosage (Y/N)	3	4	SMSreg, NDR, SRQ	NPCR, Riksstroke, MACULAREG, SWEDEHEART
	Duration/exposure (Y/N)	4	3	SMSreg, MACULAREG, NDR, SRQ	NPCR, Riksstroke, SWEDEHEART
	Therapy start/stop date (Y/N)	5	2	SMSreg, Riksstroke, MACULAREG, NDR, SRQ	NPCR, SWEDEHEART
	Is reason for stop/switch to other drug registered? (Y/N)	3	4	SMSreg, NDR, SRQ	NPCR, Riksstroke, MACULAREG, SWEDEHEART
2. 4	Is concomitant medication recorded in your registry? (Y/N)	2	5	SRQ: ‘concerning rheumatic disease’, SWEDEHEART	SMSreg, NPCR, Riksstroke, MACULAREG, NDR: Data have been linked to Prescribed Drug Registry for recognition of concomitant drugs
3. Information regarding follow-up
3. 1	Are follow-up visits recorded in your registry? (Y/N)	6	1	SMSreg, MACULAREG, NDR, SRQ, SWEDEHEART, Riksstroke	NPCR
3. 2	Are follow-up visits scheduled at regular intervals? (Y/N)	4	3	MACULAREG, NDR, SRQ: ‘when a new drug is started’, SWEDEHEART	SMSreg, NPCR, Riksstroke
	If Yes, please specify intervals
	Regularly	2	5	NDR, SWEDEHEART	SMSreg, NPCR, Riksstroke MACULAREG, SRQ
	Ad hoc	0	7		All
	Both	3	4	SMSreg, MACULAREG, SRQ	NPCR, Riksstroke, NDR, SWEDEHEART
3. 3	Are patients lost to follow-up registered?^a (Y/N)	3	4	SMSreg, Riksstroke, SRQ	NPCR, MACULAREG, NDR, SWEDEHEART: ‘No lost to follow-up based on public registry data. For SEPHIA visits there may be lost to FU’
3. 4	Are reasons for loss to follow-up registered? (Y/N)	1	6	SRQ	SMSreg, NPCR, Riksstroke, MACULAREG, NDR, SWEDEHEART
3. 5	Maximum duration of long-term follow-up?			SMSreg: ‘no limit’; NPCR: 16 y; Riksstroke: 1 y; MACULAREG: 15 y; NDR: 20 y; SRQ: ‘approx. 24 months but increasing length’; SWEDEHEART: ‘No lost to follow-up based on public registry data’
3. 6	Is ongoing medication with drug of interest registered at follow-up? (Y/N)	5	2	SMSreg, MACULAREG, NDR SRQ, SWEDEHEART: In SEPHIA	NPCR, Riksstroke
3. 7	Is it possible to follow-up teratogenic events, due to medication with drug of interest? (Y/N)	0	6		SMSreg, NPCR, Riksstroke, MACULAREG, SRQ, SWEDEHEART
3. 8	Is bio-banking of DNA or tissue samples performed at inclusion? (Y/N)	2	5	SMSreg, SWEDEHEART: ‘For patients with MI at selected sites’	NPCR, Riksstroke, MACULAREG, NDR SRQ
3. 9	Is bio-banking of DNA or tissue samples performed at follow-up? (Y/N)	2	5	SMSreg, SRQ	NPCR, Riksstroke, MACULAREG, NDR, SWEDEHEART
4. Outcome measures
4. 1	Disease activity/state (Y/N)	5	2	SMSreg, Riksstroke, NDR, SRQ, SWEDEHEART	NPCR, MACULAREG
4. 2	Organ damage, e.g. renal damage (Y/N)	3	4	NDR, SRQ, SWEDEHEART	SMSreg, NPCR, Riksstroke, MACULAREG
4. 3	Physical function (Y/N)	6	1	SMSreg, Riksstroke, MACULAREG, SRQ, SWEDEHEART, NDR: ‘physical activity’	NPCR
4. 4	Health economy/cost-effectiveness data (Y/N)	4	3	Riksstroke, NDR, SRQ, SWEDEHEART	SMSreg, NPCR, MACULAREG
4. 5	PROM (patient-reported outcome measure) (Y/N)	7	0	All (SWEDEHEART: ‘Recently started at selected sites’)
4. 6	PREM (patient-reported experiences measure) (Y/N)	4	3	SMSreg, NPCR, Riksstroke, MACULAREG	NDR, SRQ, SWEDEHEART
4. 7	Is information on deaths and cause of death recorded? (Y/N) (MPA comment: All registries can link data to Cause of Death Registry, after ethical approval)	5	2	SMSreg, Riksstroke: ‘Not cause of death’, NDR, SRQ: ‘Only information on death’, SWEDEHEART	NPCR, MACULAREG
4. 8	Quality of life (Y/N)	6	1	SMSreg, NPCR, SRQ, SWEDEHEART: ‘In SEPHIA and percutaneous valves’, NDR, Riksstroke: ‘general health condition’	MACULAREG
4. 9	Can you provide a summary list of used outcome measures in English?	6	1	SMSreg, NPCR, SRQ, SWEDEHEART, NDR: on demand, Riksstroke	MACULAREG
4. 10	Are the outcome measures the same as those used in clinical trials?	7	0	All
4. 11	Can long-term safety be followed within your registry? (Y/N)	7	0	All (SWEDEHEART: ‘Yes and no—for selected variables. Stent thrombosis and restenosis in SCAAR’)
4. 12	If yes, is linkage to other data sources required? (Y/N)	6	1	SMSreg, NPCR, MACULAREG, NDR, SRQ, SWEDEHEART: ‘Yes and no—depends on safety variables’	Riksstroke
5. Adverse event detection, processing, and reporting
5. 1	Are adverse drug reactions (ADRs) registered within registry? (Y/N)	5	2	SMSreg, MACULAREG, SRQ, SWEDEHEART: ‘Contrast media and hemodynamic reactions noted in SCAAR’, Riksstroke: intracerebral hemorrhage during anticoagulant therapy, and from thrombolytic therapy are recorded	NPCR, NDR
	If Yes, is an approved terminology for coding of ADRs used, i.e. MedDRA? (Y/N)	2	5	SMSreg, SRQ	NPCR, Riksstroke, MACULAREG, NDR, SWEDEHEART
	Does the registry provide means for web-based reporting of ADRs directly to MPA?	2	5	SMSreg, SRQ	NPCR, Riksstroke, MACULAREG, NDR, SWEDEHEART
5. 2	Are events (not ADRs) interfering with medication (surgery, accidents, etc.) registered? (Y/N)	1	6	NDR: bariatric surgery	SMSreg, NPCR, Riksstroke, MACULAREG, SRQ, SWEDEHEART

^aMPA comment: Migration and death of registered patients can be traced by registry linkage in all registries.

Table 5. Data management and quality control.

		Yes (n)	No (n)	Yes—which registry	No—which registry
1. Data capture/entry into database by:
1. 1	Web-based reporting into database? (Y/N)	7	0	All
1. 2	Is it possible for patients to enter PROMs directly into the registry by the web? (Y/N)	3	4	SMSreg, SRQ, SWEDEHEART	NPCR, Riksstroke: ‘planned for 2016’, MACULAREG, NDR: ‘Ongoing’
1. 3	Is data in the registry extracted directly from electronic health records? (Y/N)	3	4	NDR, SRQ, SWEDEHEART	SMSreg, NPCR, Riksstroke, MACULAREG
1. 4	If yes, percentage of participating health care centers with this opportunity?			NDR: 67%; SRQ: ‘From 1 EMR system’
1. 5	Is the database an integrated part of an electronic patient record system? (Y/N)	1	6	NDR	SMSreg, NPCR, Riksstroke, MACULAREG, SRQ, SWEDEHEART
2. Quality control
2. 1	Is there a specifically qualified person for quality control of data? (Y/N)	4	3	Riksstroke, SRQ, SWEDEHEART, NDR	SMSreg, NPCR, MACULAREG
	If yes, please specify qualification (MD, research nurse, inspector, etc.)	SMSreg: ‘Nurses … at the end of 2015’; Riksstroke: ‘Statistician’; SRQ: ‘… network of quality persons, MDs, nurses’; SWEDEHEART: ‘7 regional monitors are monitoring all sites’; NDR: ‘regional quality coordinators’
2. 2	Do you apply recommendations from specific international quality guidelines? (Y/N)	4	3	SMSreg, NPCR, Riksstroke, NDR	MACULAREG, SRQ, SWEDEHEART
	If yes, please specify	SMSreg: ‘… recommendations from the Swedish MS Society … based on international guidelines’; NPCR: ‘Swedish Guidelines’; Riksstroke: ‘Recommendations/guidelines from Swedish national board of health and welfare and the European Stroke Organization’; NDR: ‘ADA/EASD guideline recommendations on diabetes care are in principal adopted as these are reflected in applicable Swedish national GLs, published by the National Board of Health and Welfare, to be used in diabetes care and also treatment recommendations on use of medicinal products within the field are published by the Medical Products Agency. The latter is under revision aiming to be published in 2017’
2. 3	At what frequency is quality check performed (of raw data, delivery, etc.)?
	Regularly	4	3	Riksstroke, SRQ, SWEDEHEART, NDR: yearly	SMSreg, NPCR, MACULAREG
	Randomly	2	5	SMSreg, SRQ	NPCR, Riksstroke, MACULAREG, SWEDEHEART, NDR
	Event-driven	3	4	NPCR, MACULAREG, SRQ	SMSreg, NDR, Riksstroke, SWEDEHEART
2. 4	At what level is registry data stored?
	Local/regional	1	6	SRQ, NDR	SMSreg, NPCR, Riksstroke, MACULAREG, SWEDEHEART
	National	7	0	All
	Multinational	0	7		All
2. 5	Are missing data actively requested? (Y/N)	5	2	NPCR, Riksstroke, NDR, SRQ, SWEDEHEART	SMSreg, MACULAREG
2. 6	Do you consider it possible to request additional information from treating physician, if needed by external stakeholders (e.g. pharma companies)? (Y/N)	2	5	NDR, SWEDEHEART	SMSreg, NPCR, Riksstroke: ‘Only with a new research application to ethics committee’, MACULAREG, SRQ

Table 6. Ethical aspects.

		Yes (n)	No (n)	Yes—which registry	No—which registry
1. 1	Is there written patient information?	7	0	All
1. 2	Is a formal patient consent obtained?	5	2	MACULAREG, NDR, SRQ, SWEDEHEART (see next row)	SMSreg, Riksstroke, NPCR
	If yes, how?
	Written consent	2	5	NDR, SWEDEHEART: ‘written consent only for bio-bank’	SMSreg, NPCR Riksstroke, MACULAREG, SRQ
	Verbal consent	4	3	Riksstroke, MACULAREG, NDR, SRQ	SMSreg, NPCR, SWEDEHEART
1. 3	Does consent include an agreement to ask for follow-up information by e.g. a questionnaire, when needed from stakeholders (e.g. pharma companies)? (Y/N)	3	3	SMSreg, MACULAREG, SWEDEHEART	NPCR, Riksstroke, SRQ
1. 4	Has an ethics committee approved the working procedures/protocols of your registry? (Y/N)	5	2	SMSreg, Riksstroke, MACULAREG, NDR, SWEDEHEART	NPCR, SRQ
1. 5	Has your registry adopted any specific code of conduct, e.g. Helsinki declaration or ENCEPP’s code of conduct? (Y/N)	3	4	SMSreg, Riksstroke, NDR	NPCR, MACULAREG, SRQ, SWEDEHEART

Table 7. Legal, organizational, and financial aspects.

		Yes (n)	No (n)	Yes—which registry	No—which registry
1. Legal and organizational aspects
1. 1	If available, please provide an organogram of your registry set-up	1	0	MACULAREG
1. 2	Who owns the registry data?
	County council^a	7	0	All
	Academic institution	0	7		All
	Pharma company	0	7		All
1. 3	Is there a formal (written) agreement between participating centers regulating data handling and analytic procedures? (Y/N)	2	5	SMSreg, NDR	NPCR, Riksstroke, MACULAREG, SRQ, SWEDEHEART
1. 4	Do you collaborate with pharma companies, based on data from the registry? (Y/N)	4	3	MACULAREG, NDR, SRQ, SWEDEHEART	SMSreg: ‘But academic units may research registry data being sponsored by pharma’, NPCR, Riksstroke
1. 5	If yes, are the results used by companies for regulatory purposes? (Y/N)	4	2	SMSreg, SRQ, SWEDEHEART	Riksstroke, MACULAREG
1. 6	Is patient privacy protected by specific measures? (Y/N)	5	2	NPCR, MACULAREG, NDR, SRQ, SWEDEHEART	SMSreg, Riksstroke
1. 7	If yes, how? Data/sample coding?	NPCR: ‘remote server data stripped of identifier’; MACULAREG: ‘coding’
1. 8	Do you have a direct communication/exchange of information with national regulatory agency (MPA)? (Y/N)	6	1	NDR, SRQ, NPCR, SMSreg: ‘Adverse events reported go directly to MPA’, MACULAREG: ‘We are sharing data to compare systemic adverse events’, SWEDEHEART: ‘reporting on stent performance’	Riksstroke
2. Financial aspects
2. 1	Funding by governmental/health care authorities? (Y/N)	7	0	All
	Approx. proportions (%) of total sum from each contributing part?			SMSreg: 100%; NPCR: 90%; SRQ: 75%; Riksstroke: 100%
2. 2	By industry? (Y/N)	1	6	SRQ	SMSreg, NPCR, Riksstroke, MACULAREG, NDR, SWEDEHEART
	Approx. proportions (%) of total sum from each contributing part?			SRQ: 25%
2. 3	By research grants? (Y/N)	1	6	NPCR	SMSreg, Riksstroke, MACULAREG, NDR, SRQ, SWEDEHEART
	Approx. proportions (%) of total sum from each contributing part?	–	–

^a Regional public health authority is responsible in accordance with data protection regulations. Data collection, management, and reporting are led by a steering group nominated by the relevant health care professional organization.

Table 8. Communication and reporting.

		Yes (n)	No (n)	Yes—which registry	No—which registry
8. 1	Do you communicate results from your registry by scientific publications? (Y/N)	7	0	All
8. 2	If by other means, please specify, e.g. annual report	All registries communicate by an annual report
8. 3	How many scientific publications have been published the last two years, based on data from your registry?	SMSreg: 51; NPCR: 30 plus; Riksstroke: 40; MACULAREG: 1; NDR: 35; SRQ: 85; SWEDEHEART: ‘Approx. 100’
8. 4	When is feed-back given to reporting physician/clinics?
	In real-time (Y/N)	7	0	All
	Annually (Y/N)	7	0	All
	Ad hoc, in case of need, e.g. safety problems (Y/N)	6	1	SMSreg, Riksstroke, MACULAREG, NDR, SRQ, SWEDEHEART	NPCR