References for post-licensure studies
FVR has a solid experience in conducting phase 4 observational vaccine studies and pragmatic clinical trials. Pragmatic trials are particularly well suited for providing further evidence to National Immunization Technical Advisory Groups (NITAGs) after phase 1 to 3 trials and vaccine licensure. Real-World Evidence data ensures that outcomes in terms of public health benefits are adequately documented.
FVR experts have conducted register-based studies utilizing various study designs (cohort study, case-control study, indirect cohort method, register-based hospital-based test-negative design) in evaluating vaccine effectiveness, vaccine safety, and disease burden.
Additionally, active hospital-based test-negative design studies are particularly suitable for FVR as our RWE unit is located at the Tampere hospital campus. Tampere is the second largest urban area and the third most populous single municipality in Finland. Several large outpatient facilities are near-by.
M.D., Ph.D., University lecturer in clinical epidemiology
Chief Research Officer at FVR
arto.palmu (at) fvr.fi
+358 50 549 7113
Register data sources in Finland
All registers listed below are nationwide, linkable with each other, and affordable. Data collection in all registers is mandatory, electronic, automated, structured and, in most cases, real-time. Due to the national health insurance coverage of all permanent residents and accessible public healthcare, the registers capture the healthcare events without selection bias.
All residents of Finland have a unique Personal Identity Code (PIC). All national registers include the PIC as identifier, thus allowing unambiguous deterministic linking of data from different registers at an individual level. The PIC includes the birth date of the subject, an individual number (revealing the sex of the person) and a control character. PIC is assigned at birth or at the time a person is granted a residence permit. The PIC is permanent, except in gender transitioning.
Data for outcomes, exposure, and potential confounders and effect modifiers will be extracted from the following nationwide registers:
National Infectious Diseases Register (NIDR), maintained by the Finnish Institute for Health and Welfare (THL) since 1995 is a population- and laboratory-based surveillance system. Since 2004, the NIDR data includes the PIC. All Finnish clinical microbiology laboratories are obliged to notify positive laboratory findings for defined infectious diseases in the NIDR. Each notification includes e.g. date and place of sampling, specimen type, microbe detection method, and date of birth, sex, and municipality of residence of the patient. In addition to the laboratory notification, dentists and doctors must file a notification for certain generally hazardous or monitored communicable diseases. A public register description is available HERE >>
The Care Register for Health Care (Hilmo), a hospital discharge register maintained by THL since 1994. The register contains all inpatient hospitalizations in Finland and, since 1998, also information on outpatient visits in municipal hospitals. The discharge notifications include data on the patients such as municipality of residence, site of treatment, admission and discharge dates, type of admission (emergency/scheduled/transfer), and diagnoses recorded with ICD-10 codes (ICD-9 codes up to 1996). A separate discharge notification is reported for each visit (e.g. ER visit) or inpatient treatment at a specific ward. The data are collected locally on an ongoing basis, and transfers to the national register is performed overnight. The data includes the PIC and can be linked with other individual register data. A public register description is available HERE >>
The Register of Primary Health Care Visits (Avohilmo) maintained by THL contains data on outpatient primary health care visits in public health care since 2011. Since 2021, also most private health care providers are covered. The data includes e.g. date, place, and time of the visit/contact and reason/diagnoses (recorded with ICD-10 codes or ICPC-2 codes). The data includes the PIC and can be linked with other individual register data. The data dispatch from the health care centers is scheduled to occur every night. A public register description is available HERE >>
The National Vaccination Register (NVR), maintained by THL since 2009, was established as part of the Register of Primary Health Care Visits (Avohilmo/THL) (Baum et al. 2017). The data is comprehensive since 2011. The NVR includes all vaccinations given in public primary health care and it is increasingly covering also vaccinations administered in the private health care and specialist medical care (the latter through Hilmo).
The Medical Birth Register, maintained by THL since 1987, with several further reforms includes versatile data on deliveries and births in Finland. The data includes PIC and can be linked with other individual register data. A public register description is available HERE >>
The Social Insurance Institutions (KELA) benefits registers include data on decisions on reimbursement of health care costs of the individual citizens covered by the national health insurance. These include e.g. reimbursements for antimicrobial drugs and entitlement to special reimbursements on medical expenses such as entitlement to reimbursement of drugs for defined chronic diseases and of immunosuppressant drugs. Special reimbursement decisions can be used for identification of chronic diseases. The data includes the PIC and can be linked with other individual register data.
Kanta Services (KELA), Prescription Centre and Patient Data Repository. The Prescription Centre contains data on electronical prescriptions for medicines comprehensively since 2017. The Patient Data Repository is a national information system service for archiving electronic patient data produced. The majority of public health care providers had joined the Kanta Patient Data Repository in 2015 and since November 2021 it has also been mandatory for private health care providers to join. Kanta Services is a cooperative effort of KELA, THL, the Digital and Population Data Services Agency (DVV), the Ministry of Social Affairs and Health and the National Supervisory Authority for Welfare and Health Valvira, as well as social welfare and healthcare operators, pharmacies and system suppliers. Kanta is updated near real-time. The health and social data in the Kanta Services is available for secondary use, read more HERE >>
The Digital and Population Data Services Agency (DVV) maintains a Population Information System (PIS), a computerized national register that contains basic information about Finnish citizens and foreign citizens residing in Finland on a permanent basis. The information in the system is used throughout the information services and management of the Finnish society. Personal data recorded in the system includes e.g. the date and country of birth, date of death (if applicable), municipality of residence and place of residence/address. Aggregated population data are publicly available, read more HERE >>
Additional registers available for research purposes include the Care Register for Social Care at THL, Cancer register (THL), various registers of Statistics Finland, and many others.
Pragmatic trial references
Palmu AA, Jokinen J, Borys D, Nieminen H, Ruokokoski E, Siira L, Puumalainen T, Lommel P, Hezareh M, Moreira M, Schuerman L, Kilpi TM. Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial. Lancet. 2013 Jan 19;381(9862):214-22. doi: 10.1016/S0140-6736(12)61854-6. Epub 2012 Nov 16.
Hollingsworth R, Palmu A, Pepin S, Dupuy M, Shrestha A, Jokinen J, Syrjänen R, Nealon J, Samson S, De Bruijn I. Effectiveness of the quadrivalent high-dose influenza vaccine for prevention of cardiovascular and respiratory events in people aged 65 years and above: rationale and design of a real-world pragmatic randomized clinical trial. Am Heart J. 2021 Mar 12:S0002-8703(21)00072-7. doi: 10.1016/j.ahj.2021.03.007. https://clinicaltrials.gov/ct2/show/NCT04137887. Manuscript with trial results has been submitted.
The authors shown in bold are FVR employees.
Observational study references
Palmu AA, Rinta-Kokko H, Nohynek H, Nuorti JP, Kilpi TM, Jokinen J. Impact of ten-valent pneumococcal conjugate vaccine on pneumonia in Finnish children in a nation-wide population-based study. PLoS One. 2017 Mar 1;12(3):e0172690. doi: 10.1371/journal.pone.0172690. eCollection 2017.
Rinta-Kokko H, Auranen K, Toropainen M, Nuorti JP, Nohynek H, Siira L, Palmu AA. Effectiveness of 10-valent pneumococcal conjugate vaccine estimated with three parallel study designs among vaccine-eligible children in Finland. Vaccine. 2020 Feb 5;38(6):1559-1564. doi: 10.1016/j.vaccine.2019.11.049.
Halme J, Syrjänen RK, Baum U, Palmu AA. Effectiveness of trivalent influenza vaccines against hospitalizations due to laboratory-confirmed influenza a in the elderly: Comparison of test-negative design with register-based designs. Vaccine. 2022 Jul 29;40(31):4242-4252. doi: 10.1016/j.vaccine.2022.05.080. Epub 2022 Jun 9.
Rondy M, Gherasim A, Casado I, Launay O, Rizzo C, Pitigoi D, Mickiene A, Marbus SD, Machado A, Syrjänen RK, Pem-Novose I, Horváth JK, Larrauri A, Castilla J, Vanhems P, Alfonsi V, Ivanciuc AE, Kuliese M, van Gageldonk-Lafeber R, Gomez V, Ikonen N, Lovric Z, Ferenczi A; I-MOVE+ hospital working group; Moren A. Low 2016/17 season vaccine effectiveness against hospitalised influenza A(H3N2) among elderly: awareness warranted for 2017/18 season. Euro Surveill. 2017 Oct;22(41):17-00645. doi: 10.2807/1560-7917.ES.2017.22.41.17-00645.
Hovi P, Palmu AA, Nieminen TA, Artama M, Jokinen J, Ruokokoski E, Lassila R, Nohynek H, Kilpi T. Incidence of sinus thrombosis with thrombocytopenia-A nation-wide register study. PLoS One. 2023 Feb 24;18(2):e0282226. doi: 10.1371/journal.pone.0282226. eCollection 2023.
Gehrt L, Laake I, Englund H, Nieminen H, Benn CS, Feiring B, Trogstad L, Palmu AA, Sørup S. Hospital Contacts for Infectious Diseases Among Children in Denmark, Finland, Norway, and Sweden, 2008-2017. Clin Epidemiol. 2022 Apr 29;14:609-621. doi: 10.2147/CLEP.S355193. eCollection 2022.
The authors shown in bold are FVR employees.