Biologisten lääkkeiden kustannusvaikuttavuus nivelreuman hoidossa : järjestelmällinen kirjallisuuskatsaus

Rheumatoid arthritis (RA) is a chronic autoimmune disease with prevalence of 0.8% among Finnish adult population. Consequent medical treatment, joint replacement surgery and productivity losses lead to significant expenses for society. While biological treatments for RA are costly, they can improve patients' quality of life and work participation. Economic evaluations provide information on the benefits and costs of these expensive treatments to aid optimal utilization of limited healthcare resources. This master`s thesis comprises the description of the Finnish Current Care Guidelines for RA, the cost of biological treatments and the principles of economic evaluations and health technology assessment. A systematic literature review was performed to identify existing studies examining the cost-effectiveness of biological treatments for RA. Of the 4890 references found with the literature search, 38 original studies and 9 previous systematic reviews were included in the current systematic literature review. Details of the methods as well as information on treatments, costs, benefits and incremental cost-effectiveness were extracted. Quality of the original studies was evaluated using quality assessment tools. Ninety percent (34/38) of the original studies used cost-utility modeling approach. Quality of life estimates were derived from RA specific health assessment questionnaire in a majority of the studies. Based on the current systematic literature review, the evidence on the cost-effectiveness of biological treatments is inconsistent. The incremental cost-effectiveness of the tumor necrosis factor (TNF) blockers was 13 500-772 000 €/ quality adjusted life year (QALY) in comparison to conventional disease modifying anti rheumatic drugs (DMARD) among patients without previous treatment with DMARDs. Several studies reported incremental cost-effectiveness ratios over 100 000 €/QALY in this population. Among patients with insufficient response to DMARDs, TNF blockers provided incremental cost-effectiveness ratios between 6 700 and 317 000 €/QALY. In most studies Rituximab was found to be a cost-effective alternative in contrast to other treatments among patients with insufficient response to TNF blockers. Biological treatments are not cost-effective among patients naïve to conventional DMARDs. Meanwhile, in patients with previous DMARD failure TNF-blockers might be cost-effective. The evidence on the cost effectiveness of biological treatments supports Finnish Current Care Guidelines. The quality assessment of the included studies revealed several sources of bias, consequently reducing the validity of the studies. Only a few of the conference abstracts in current subject has been published later as an article indicating existence of reporting bias. This study has several strengths. First, a comprehensive literature search was performed. Second, the quality of included studies was carefully evaluated. Finally, the methods and reporting are transparent. Weakness of the current study is one person extracting data and assessing the quality of the studies, which may reduce the reliability of this study. This systematic literature review is a basis for future studies examining cost-effectiveness of biological treatments in Finnish healthcare system.Nivelreuma on krooninen autoimmuunisairaus, jonka esiintyvyys suomalaisessa aikuisväestössä on noin 0,8 %. Yhteiskunnalle aiheutuu merkittäviä kustannuksia nivelreumapotilaiden lääkehoidon, tekonivelleikkausten ja menetetyn työpanoksen seurauksena. Nivelreuman hoidossa käytettävät biologiset lääkkeet ovat huomattavan kalliita, mutta parantavat nivelreumaa sairastavien elämänlaatua ja työkykyä. Tietoa näiden kalliiden lääkkeiden kustannuksista ja hyödyistä tarvitaan voimavarojen kohdentamista koskevan päätöksenteon tueksi. Tässä Pro gradu -tutkielmassa kuvataan nivelreuman tämänhetkinen hoitokäytäntö Suomessa ja biologisen lääkehoidon kustannukset sekä esitellään taloudellisen arvioinnin ja terveyden huollon menetelmäarvioinnin keskeiset periaatteet. Järjestelmällisen kirjallisuuskatsauksen avulla etsitään tämänhetkinen saatavilla oleva näyttö biologisten lääkkeiden kustannusvaikuttavuudesta nivelreumassa. Kirjallisuushaulla löydettiin 4890 viitettä, joista järjestelmälliseen kirjallisuuskatsaukseen valittiin 38 alkuperäistutkimusta ja 9 aiempaa järjestelmällistä kirjallisuuskatsausta. Tutkimuksista kerättiin tiedot käytetyistä arviointimenetelmistä, vertailtavista hoidoista, niiden kustannuksista ja hyödyistä sekä inkrementaalisesta kustannusvaikuttavuudesta. Alkuperäistutkimusten laatu arvioitiin laadunarviointityökaluja käyttäen. Alkuperäistutkimuksista 90 % (34/38) perustui kustannusutiliteettimallinnukseen. Elämänlaatu oli suurimmassa osassa tutkimuksista johdettu nivelreuman toimintakykymittari HAQ:sta. Järjestelmällisen kirjallisuuskatsauksen perusteella näyttö biologisten lääkkeiden kustannusvaikuttavuudesta on ristiriitaista. Tuumorinekroositekijän (TNF) salpaajien inkrementaalinen kustannusvaikuttavuus tavanomaisiin reumalääkkeisiin verrattuna oli 13 500-772 000 € laatupainotettua elinvuotta (QALY) kohden varhaista nivelreumaa sairastavilla potilailla, joita ei oltu aiemmin hoidettu tavanomaisilla reumalääkkeillä. Monissa tutkimuksissa havaitut inkrementaaliset kustannusvaikuttavuudet olivat tässä potilasryhmässä yli 100 000 €/QALY. Potilailla, jotka eivät ole saaneet riittävää hoitovastetta tavanomaisilla reumalääkkeillä, TNF-salpaajien inkrementaalinen kustannusvaikuttavuus oli 6 700-317 000 €/QALY. Rituksimabi havaittiin useissa tutkimuksissa kustannusvaikuttavaksi muihin hoitovaihtoehtoihin verrattuna potilailla, joiden aiempi TNF-salpaajahoito oli epäonnistunut. Varhaisessa nivelreumassa, jota ei ole aiemmin hoidettu tavanomaisilla reumalääkkeillä biologiset lääkkeet eivät olleet kustannusvaikuttavia. Sen sijaan potilailla, jotka eivät aiemmin ole saaneet hoitovastetta tavanomaisilla reumalääkkeillä, TNF-salpaajat saattavat olla kustannusvaikuttavia tavanomaisiin reumalääkkeisiin verrattuna. Tulokset biologisten lääkkeiden kustannusvaikuttavuudesta ovat linjassa suomalaisten nivelreuman hoitosuositusten kanssa. Tehtyjen tutkimusten laadun arvioinnissa havaittiin useita mahdollisia harhan lähteitä, jotka saattavat vaikuttaa tutkimusten validiteettiin. Julkaisuharhan olemassaolosta antaa viitteitä se, että vain pieni osa aihepiiriä käsittelevistä konferenssiabstrakteista oli julkaistu artikkeleina. Tämän tutkimuksen vahvuutena on kattava järjestelmällinen kirjallisuushaku, tehtyjen tutkimusten laadunarviointi sekä käytettyjen menetelmien ja tulosten läpinäkyvä raportointi. Tutkimuksen heikkoutena on se, että tietojenkeruun ja tutkimusten laadun arvioinnin teki yksi henkilö, joka saattaa vaikuttaa tutkimuksen reliabiliteettiin. Tämä järjestelmällinen kirjallisuuskatsaus antaa hyvän lähtökohdan tuleville suomalaisiin aineistoihin perustuville biologisten lääkkeiden kustannusvaikuttavuustutkimuksille

A Novel Construct To Measure Employees’ Technology-Related Experiences of Well-Being : Empirical Validation of the Techno-Work Engagement Scale (TechnoWES)

Because of the current developments in digitalization, novel technological solutions have changed work processes and accordingly influenced employee well-being. There is a lack of measures of positive well-being experiences regarding technology at work. Therefore, the current study introduces a novel construct—namely techno-work engagement—and a scale to measure it. Techno-work engagement is defined as a positive experience of well-being regarding the use of technology at work. The study tested the factorial, discriminant, and convergent validity of the scale, TechnoWES-9. Using data from two samples, the factor structure of the construct was analyzed with a confirmatory factor analysis (CFA). In addition, in Study 2, CFAs, correlations, and mean differences were used to assess the discriminant and convergent validity and whether the shorter scale can be used as an alternative to the longer one. The results concerning the factorial validity support the view that techno-work engagement is better represented as a three-factor than as a unidimensional construct. Like TechnoWES-9, TechnoWES-3 is positively correlated with technology-related job resources; also, both can be discriminated from technostress. TechnoWES-9, although not flawless, is a reliable and valid indicator of techno-work engagement, and the shorter version can be used as its alternative. In the future, the relationships between work engagement, technostress, and techno-work engagement could be measured and the scale could be tested in different countries and occupations

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer : a prospective study

BACKGROUND: The prognostic significance of isolated tumour cells (ITCs) in the sentinel nodes (SNs) is controversial in early breast cancer, and some centres have abandoned immunohistochemistry to detect ITCs. METHODS: Patients with unilateral pT1N0 breast cancer, operated between February 2001 and August 2005 at a university hospital were included in this prospective, population-based cohort study. Survival of 936 patients with or without isolated tumour cells (ITC) in their SNs were compared with the log-rank test and Cox regression analysis. RESULTS: Eight hundred sixty one (92.0%) patients were ITC-negative (pN0i-) and 75 (8.0%) ITC-positive (pN0i+). Patients with ITC-positive cancer received more frequently adjuvant systemic therapies than those with ITC-negative cancer. The median follow-up time was 9.5 years. Ten-year distant disease-free survival was 95.3% in the pN0i-group and 88.8% in the pN0i+ group (P = 0.013). ITCs were an independent prognostic factor in a Cox regression model (HR = 2.34, 95% CI 1.09-5.04; P = 0.029), together with tumour Ki-67 proliferation index and diameter. ITCs were associated with unfavourable overall survival (P = 0.005) and breast cancer-specific survival (P = 0.001). CONCLUSIONS: We conclude that presence of ITCs in the SNs is an adverse prognostic factor in early small node-negative breast cancer, and may be considered in the decision-making for adjuvant therapy.Peer reviewe

Labor Market Participation Before and After Long-Term Part-Time Sickness Absence in Finland A Population-Based Cohort Study

Objective: To examine trends in labor market participation among those with long-term part-time or long-term full-time sickness absence. Methods: Finnish population-based cohort study including 3406 individuals with greater than 30-day part-time sickness absence in 2011 and 42,944 individuals with greater than 30-day full-time sickness absence in 2011. Results: Compared to previous years, the rates of sickness absence and vocational rehabilitation increased after 2011 in both groups. Sickness absence rate was higher in 2012 in the full-time sickness absence group than in the part-time sickness absence group. An increasing trend in unemployment after 2011 was observed in both groups, but the absolute level of unemployment was higher in the full-time sickness absence group. Conclusion: Long-term part-time sickness absence seems to mark a decline in labor market participation, but the decline is smaller than that in employees with full-time sickness absence.Peer reviewe

Työn uudet muodot ja työkyvystä huolehtiminen : terveyskäyttäytyminen etätyössä

Työn uudet muodot ja työkyvystä huolehtiminen - terveyskäyttäytyminen etätyössä -tutkimus valottaa etätyötä terveyskäyttäytymisen ja työkyvyn näkökulmista. Projektin suunnittelu alkoi jo ennen koronapandemiaa, koska organisaatioilla oli käytännön tarve saada tietoa terveyskäyttäytymisestä etä- ja monipaikkaisessa työssä. Koronapandemia nosti aiheen entistäkin ajankohtaisemmaksi ja tutkimuksen tuottamalle tiedolle tuli suuri tarve. Raportissa käsittelemme henkilöstön kokemuksia etätyöstä, etätyön sujumista, terveyskäyttäytymistä sekä stressiä, työkykyä ja palautumista. Kuvaamme myös, millä tavoin työnantajat ja johto voivat tukea myönteistä terveyskäyttäytymistä ja työkykyä, kun työntekijät työskentelevät etänä teknologiavälitteisesti. Organisaatiot kehittivät työterveyshuollon ja työsuojelun tuella nopeasti uusia ratkaisuja koronan aikaisessa poikkeustilanteessa. Tutkimuksen tarjoamia oppeja etä- ja monipaikkaisen työn organisointiin ja johtamiseen voidaan hyödyntää laajasti myös jatkossa

The Cost-Effectiveness of Biologics for the Treatment of Rheumatoid Arthritis : A Systematic Review

Background and Objectives Economic evaluations provide information to aid the optimal utilization of limited healthcare resources. Costs of biologics for Rheumatoid arthritis (RA) are remarkably high, which makes these agents an important target for economic evaluations. This systematic review aims to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically. Methods A literature search covering Medline, Scopus, Cochrane library, ACP Journal club and Web of Science was performed in March 2013. The cost-utility analyses (CUAs) of one or more available biological drugs for the treatment of RA in adults were included. Two independent investigators systematically collected information and assessed the quality of the studies. To enable the comparison of the results, all costs were converted to 2013 euro. Results Of the 4890 references found in the literature search, 41 CUAs were included in the current systematic review. While considering only direct costs, the incremental cost-effectiveness ratio (ICER) of the tumor necrosis factor inhibitors (TNFi) ranged from 39,000 to 1 273,000 (sic)/quality adjusted life year (QALY) gained in comparison to conventional disease-modifying antirheumatic drugs (cDMARDs) in cDMARD naive patients. Among patients with an insufficient response to cDMARDs, biologics were associated with ICERs ranging from 12,000 to 708,000 (sic)/QALY. Rituximab was found to be the most cost-effective alternative compared to other biologics among the patients with an insufficient response to TNFi. Conclusions When 35,000 (sic)/QALY is considered as a threshold for the ICER, TNFis do not seem to be cost-effective among cDMARD naive patients and patients with an insufficient response to cDMARDs. With thresholds of 50,000 to 100,000 (sic)/QALY biologics might be cost-effective among patients with an inadequate response to cDMARDs. Standardization of multiattribute utility instruments and a validated standard conversion method for missing utility measures would enable better comparison between CUAs.Peer reviewe

Effectiveness and drug survival of TNF-inhibitors in the treatment of psoriatic arthritis : A prospective cohort study

Background and objectives: Tumor necrosis factor (TNF)-inhibitors are used to treat psoriatic arthritis (PsA), but only a limited number of observational studies on this subject have been published thus far. The aim of this research was to analyze the effectiveness and drug survival of TNF-inhibitors in the treatment of PsA. Methods: PsA patients identified from the National Register for Biologic Treatment in Finland (ROB-FIN) starting their first, second, or third TNF-inhibitor treatment between 2004 and 2014 were included. Effectiveness was measured using ACR and EULAR response criteria and modeled using ordinal logistic regression. Treatment persistence was analyzed using Kaplan-Meier survival analysis and Cox proportional hazards model. Results: The study comprised 765 patients and 990 TNF-inhibitor treatment courses. EULAR moderate treatment responses at 6 months were achieved by 68% and 37% of the users of the first and the second or the third biologic, respectively. The probabilities of discontinuing the treatment within 12 and 24 months were 20% and 28%, respectively. Adjusted treatment responses to all TNF-inhibitors were similar; however, co-therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) was not associated with better effectiveness. Adalimumab [hazard ratio (HR) = 0.62; 95% confidence interval (CD: 0.44-0.88] was superior to infliximab in drug survival while etanercept (HR = 0.77, 95% CI: 0.55-1.1) and golimumab (HR = 0.75, 95% CI: 0.46-1.2) did not differ from it. Co-medication with csDMARDs did not statistically improve drug survival. Conclusion: All available TNF-inhibitors showed similar treatment responses with or without csDMARDs. Adalimumab was associated with better drug survival when compared to infliximab. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe