Browsing by Subject "Socialfarmaci"

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  • Ruohonen, Iida (Helsingin yliopisto, 2020)
    Tiivistelmä – Referat – Abstract 15D is a generic, 15-dimensional instrument for measuring health-related quality of life (HRQoL). 15D instrument has been used in multiple studies evaluating the effectiveness of medical interventions in Finland and abroad. 15D-instrument is a self-administered questionnaire traditionally administered in a paper-and-pencil format. With the emergence of novel technologies, electronic modes of delivery of the 15D instrument are becoming increasingly common as methods for data collection. However, there are no previous studies evaluating electronic modes of delivery of the 15D instrument. In previous studies, electronic instruments measuring patient-reported outcomes have shown strong measurement equivalence and high acceptability. The aim of this study is to evaluate acceptability and measurement equivalence of electronic delivery modes of the 15D instrument. A repeated measures, randomized cross-over study was conducted in the Department of Otorhinolaryngology at Helsinki University Hospital during April, May and June of 2019. A total of 160 outpatients who participated in the study were randomized into four groups of 40 patients. Every participant filled two delivery modes of the 15D instrument: a single paper-and-pencil questionnaire and one out of two electronic questionnaires provided in the study. The two electronic delivery modes delivered in the study were a web-based questionnaire and a mobile app-based questionnaire. The order and the mode of the administration varied between the groups. The patients filled the first questionnaire before the doctor’s appointment at the study site. The patients were then asked to fill the second questionnaire after the doctor’s appointment at home within 3 days after the first administration. Information about acceptability concerning different delivery modes were collected using an end-of-study questionnaire. As a part of determining patient acceptability, response rates for different delivery forms and mode preferences were examined. Measurement equivalence was assessed by intra class correlation coefficients (ICCs) and comparison of mean and median for 15D scores and weighted kappa for item scores. Paired observations were also visually analysed with Bland-Altman plots. Subgroup analyses were conducted for identifying differences in observed patient characteristics (age, sex, base-line HRQoL). 86 participants (females 53.5 %; males 46.5 %) aged 18 to 80 (mean ± SD: 48.2 ± 15.7) filled both questionnaires of the 15D instrument resulting in an overall response rate of 54.1%. Response rates for filling both questionnaires were lower in both groups that filled electronic forms at home (41.0 % for mobile app-based and 52.5 % for web-based questionnaires) than in the paper-and-pencil groups (60.0 % and 62.5 %). Overall 74.1 % preferred the electronic delivery mode compared to 16.5 % preferring the paper-and-pencil mode. Statistically significant differences favouring the web-based form over the paper-and-pencil form were observed in the speed of use (p = 0.002) and in the possibility to edit answers (p = 0.018). Similarly, mobile app-based form was favoured over paper-and-pencil group in the possibility to edit answers (p = 0,041). In terms of measurement equivalence for 15D index scores, high association across paper-and-pencil and web-based questionnaires (ICC: 0.910 [Cl 95 % 0.794-0.962] and ICC: 0.935 [Cl 95 % 0.862-0.971]) and high to moderate across paper-and-pencil and mobile app-based questionnaires (ICC: 0.949 [Cl 95 % 0.883-0.978] and ICC: 0.928 [Cl 95 % 0.601-0.980]) were observed. A clinically important and a statistically significant difference in mean 15D scores was identified in the paper-mobile app group. A statistically significant but not clinically important difference in medians was observed in mobile app-paper group with participants returning the second delivery form in time. This study provides strong evidence supporting the use of electronic delivery modes of the 15D instrument regarding measurement equivalence and patient acceptability. However, differences in electronic delivery modes may have an impact on measurement equivalence and representativeness of study participants. In this study, a small sample size and limited data on study participants limit the generalizability of the results. Most effective ways of collecting data electronically concerning all age and patient groups must be identified in future studies. Electronic data collection methods offer many opportunities for utilising HRQoL data. For example, it is important to assess whether HRQoL-instruments can be used as clinical tools in the future.
  • Metiäinen, Tiia (Helsingfors universitet, 2015)
    Health related issues are largely regulated at EU Member State level, whereas areas such as internal market and competition fall mainly under the remit of European Union competence. This creates tension not only between legislation governing health and that concerning internal market but also between national and EU legislation. Here the Court of Justice of the European Union (CJEU) plays a key role in developing case-law through its judgments, defining further interpretation both on European and national level. An example of a sector operating at the interphase between public health and internal market interests is community pharmacy, which was chosen as the focus area of the study. The aim of this master's thesis was, through the case-study example of the regulation of pharmacy establishment, ownership and distribution in EU Member States, to perform a documentary analysis on related CJEU judgments, focusing on statements present in them referring to public health and internal market, discussing potential impacts on the community pharmacy sector as well as relating the outcomes to the broader context of European health policy with reference to existing literature. The study material consisted of publicly available documentation related to four judgments (Case C-531/06, Joined Cases C-171/07 and C-172/07, Joined Cases C-570/07 and C-571/07 and Case C-367/12) that were made between the years 2009 and 2014, the first proceedings initiating in 2006. The prevalence and variety of statements related to public health were found to be much higher in the documents analysed compared to those relating to internal market. The most common argumentation present in the judgments was related to the statement that regulation of ownership of community pharmacies can be justified by public health reasons, deriving from the professionalism inherent to pharmacists as well as ensuring balance between public health and economic interests. This transmits a clear message of the importance of public health and indeed the Court has been perceived as a balancing force to the union's liberalisation agenda. Following this it seems unlikely that the interpretation for national regulation would change in the near future, meaning that Member States should be able to maintain community pharmacy regulation, to the extent that it is implemented in a consistent manner. However, there has been indication of other routes being used to push for the liberalisation agenda and therefore it continues being a part of the debate both at European and national level. The findings of this study support literature suggesting that spillover is taking place in relation to the Court of Justice and health. Furthermore, it has been clearly demonstrated that even though officially the EU has very limited competence (authority) in health, its influence on European health policy is in fact highly significant, taking place to a large extent via routes other than those officially assigned to it in relation to health in particular. Whether this is intentional or unintentional, it does not change the fact that health policy is being influenced. When it happens without explicit intention, the processes lose transparency and are driven by other, potentially competing agendas. Therefore it would be important to assess whether the decision making processes and other processes currently shaping the European healthcare policy are in line with what was originally intended and re-evaluate whether this dynamic is the preferred way to proceed in the future.
  • Kumpula, Eeva-Katri (Helsingfors universitet, 2009)
    Anticholinergic medicines are commonly used to treat e.g. incontinence. These medicines have side effects, which may cause and also exacerbate e.g. dryness of the mouth, increased heart rate, and even cognitive impairment. Older people may be more at risk for these side effects as they may be experiencing similar symptoms as a natural effect of aging, and because they may be using several medicines causing these effects. Older people often have a high medicine burden and also a high disease burden. Measuring anticholinergic effects to change medicine regimens and to reduce the symptoms is difficult as there is no golden standard method. This thesis investigated the published methods available for estimating anticholinergic burden in the literature review part, and used one anticholinergic scoring system, the Anticholinergic Risk Scale, in a cross-sectional study to test the effects of anticholinergics on mortality in 1004 older institutionalised patients from Helsinki area public hospitals. Cross-tabulations and Kruskal-Wallis or Chi square methods were used to detect differences between variables such as nutritional status or certain diagnoses when the patients were stratified according to their anticholinergic use. Cox Proportional Hazard regression, the logrank test and Kaplan-Meier curve were used to investigate the effects of anticholinergics on 5-year all-cause mortality. An in vitro serum assay and seven anticholinergic scoring systems were identified in the literature search. Also, 17 anticholinergic lists were identified, which covered 278 medicines, of which 21 appeared on at least eight of the lists. In the empirical study, the women's (n = 745) mean (± SD) age was 83.35 (± 9.99) years, and they were older than the men (n = 241, mean age ± SD 75.11 ± 11.48, p < 0.001). The 1004 patients (response rate 70 %) were using a mean (± SD) number of 7.1 ± 3.4 regular medicines (range 0-20). 455 patients used no anticholinergics, 363 had some anticholinergic burden (score 1 or 2), and 186 had a high burden, with anticholinergic scores of 3 or more. The mean ARS score (± SD) was 1.2 ± 1.5 (range 0-10). When three anticholinergic lists were compared, all three lists identified only 280/791 of patients who were anticholinergic users according to at least one list. No association was found between anticholinergic medicine use and mortality. There are several methods available for measuring anticholinergic burden, but there is a need for a consensus method. This was highlighted by the lack of agreement on medicines on different lists and when three anticholinergic lists tested identified different patients when compared to each other. Anticholinergic use was common in this frail, older patient sample, but no effect on mortality was shown in this study setting. The cross-sectional nature of the data limits the reliability of the study, and any conclusions beyond older patients in Helsinki area must be done very cautiously. Future research should define anticholinergics better and investigate their possible effect on mortality in a prospective, randomised, and controlled setting.
  • Hou, Kathy (Helsingin yliopisto, 2021)
    Antidepressant use among children and adolescents has become more common in many countries. The prevalence of antidepressants is higher for boys but during adolescence girls’ have a higher antidepressant prevalence. In previous studies, the prevalence of selective serotonin re-uptake inhibitors (SSRI) has increased. The aim of this study was to investigate antidepressant use among Finnish children and adolescents aged 1–17 years during 2008–2019. The differences of antidepressant use in different age groups and genders were investigated. Furthermore, the secondary objective was to examine the trends in prevalence and costs of the five most commonly used antidepressant agents. This was a nation-wide register study. The data for this study was from Kelasto which is a statistical database maintained by the Social Insurance Institution of Finland. The extracted data was from 2008–2018 and included each persons’ age, gender, dispensed drug and costs. The data extracted was for 1–17-year-olds who had been dispensed reimbursed antidepressants from community pharmacies. The data was analyzed with Microsoft Office’s Excel program. The results were transferred in to tables and reported as prevalences by age groups, genders, antidepressants and costs. The prevalence of antidepressant use among children and adolescents was 5,0 per 1000 in 2008 and it increased to 10,3 by 2018. In the youngest age group of 1–6-year-olds, antidepressant use decreased. Antidepressant use increased slightly among 7–12-year-olds. Antidepressant use increased the most among 13–17-year-olds. 13–17-year-old girls had the higher antidepressant use prevalence throughout the study. The same group had a 2,4-fold increase in prevalence during the study period which accounted for the biggest increase in the study. The most used group of antidepressants was SSRIs. The total cost for antidepressants among children and adolescents increased by 73,7 % during the study period. The most commonly used antidepressant agents were fluoxetine, sertraline, escitalopram, mirtazapine, and venlafaxine, respectively. Fluoxetine was the most used agent throughout the study. In 2014, sertraline surpassed escitalopram and became the second most used antidepressant agent. Escitalopram and venlafaxine’s cost per user decreased during the study. The cost per user stayed stable for mirtazapine. Fluoxetine and sertraline’s cost per user increased. The Kelasto database does not include data on indications for prescriptions. The prevalence of antidepressants does not necessarily correlate directly to depression among children and adolescents because antidepressants can be used to treat other diseases. More studies need to be conducted on different off-label uses for antidepressants among children and adolescents. This study only investigated the trends on cost for the five most commonly used antidepressants. Further studies on antidepressant costs among children and adolescents are needed. Additionally, it is essential to investigate the reasons for the increase in antidepressant use among children and adolescents.
  • Luhtanen, Päivi (Helsingin yliopisto, 2020)
    The pharmacy operations are strictly regulated in Finland and the operation of a pharmacy business requires a licence. Number of community pharmacies has stayed quite steady for the past 10 years. At the end of the year 2019 there were 817 pharmacies or their subsidiaries in Finland. The number of pharmacies is expected to increase, since 29 new pharmacies has been established since 2016. The inspection of pharmacies is a part of the legal duties of the Finnish Medicines Agency. In Finland, pharmacies are inspected based on a risk assessment, as often as it is necessary to ensure appropriate operations of a pharmacy. During a pharmacy inspection, the focus is on operations that are critical to drug safety and medication safety. The aim of an inspection is to make sure that pharmacy operations comply with the regulations. There are only few studies made on remote inspection of the pharmacies. The Finnish Medicines Agency hasn’t made remote pharmacy inspections before. The aim of this study was to develop, validate and test a questionnaire, which could be used to inspect community pharmacies remotely and to develop and test a process for remote inspections. The study was done in two parts. In the first part, a draft of the questionnaire was developed by studying the regulations and laws regulating the operations of a pharmacy and by using a content analysis. The material for the content analysis was a pre-inspection questionnaire form, answers to the pre-inspection questionnaires and defect lists of the inspection reports of those pharmacies (n=37), which had answered to the pre-inspection questionnaire before pharmacy inspection in 2019. Content of the pre-inspection questionnaire and the answers of pre-inspection questionnaire were compared to the content of the defect lists of inspection reports. The aim of the comparison was to find out how the existing pre-inspection questionnaire could be utilized when developing the questionnaire for the remote pharmacy inspections. In addition, the listed defects of the inspection reports were categorized to explore what were the most common defects observed during pharmacy inspections. In the second part of the study, the content of the developed questionnaire was validated by using a three round modified Delphi survey. Seven experts with good knowledge of the pharmacy inspections were chosen to the Delphi panel. The aim of the Delphi rounds was to achieve full consensus among the experts about the content of the questionnaire. Alongside the Delphi rounds, a process to remote inspect a pharmacy was developed. The remote inspection questionnaire and the process were tested internally in the Finnish Medicines Agency at the end of the second stage of study. The draft of the questionnaire included 15 sections and 164 questions. Based on the comments received during the Delphi rounds, the content of the questionnaire was modified. On the third Delphi round a full consensus of the content of the questionnaire was achieved among the experts. The final questionnaire for the pharmacy remote inspection included 14 sections and 184 questions. The process of the remote pharmacy inspection follows the procedure of an on-site pharmacy inspection. In the internal test, the process of the remote inspection was found to be a good way to inspect pharmacies remotely. The remote inspection process is a new way to inspect pharmacies. With the remote inspection, it is possible to find out the most common defects on the pharmacy operations by using the questionnaire and contact calls. The remote inspection questionnaire and the process need to be further tested to ensure that the process is optimal from the perspective of the authority and the pharmacies.
  • Saksi, Outi (Helsingfors universitet, 2016)
    The development and maintenance of the pharmaceutical workforce's know-how ensure the availability of medicinal consulting and service. Healthcare personnel in Finland are bound by law to uphold and improve their workmanship. Furthermore, a pharmacy owner is legally obliged to keep track of the development of healthcare professional's skills and to ensure the staff's sufficient participation for continuing education (CE). Pharmacists' development and maintenance of professional skills is not linked to preservation of professional competence in Finland. The goal of this study was to get a general view of the development and maintenance of professional skills of pharmacists working in community pharmacies as well as applicaple methods. Additionally, the aim was to determine whether community pharmacists' development of professional skills is systematical. As background material in this thesis, a sub-material of an online study regarding development and maintenance of professional skills was used, which was carried out by the Finnish Pharmacists' Association in September 2013 and it consists of 430 pharmacists' responses who work in community pharmacies. The results show that the methods community pharmacists use to develop and maintain their professional skills are diverse. The recommendation by the authorities is at least three days of CE for one person per year but the majority (83 %) of the participants of this study didn't follow it. Some of the pharmacists develop and maintain their professional skills by attending diligently CE's while the number of pharmacists who do not attend any CE has risen. The number of pharmacists who did not participate in any CE was 26 % in the year prior to this study. The results might point to changes in learning methods or the decline of CE activity. The results of this thesis show that development of professional skills was not systematical in the majority of the pharmacies. An annual personal develompent plan was drawn up in 24 % of the respondents' workplaces and development discussions were had in few. Independent planning, monitoring and evaluation of their own professional skill development were done by 10 % of the pharmacists. The planning of professional skill development was not found to impact CE participation. Development discussions and training schedules that are drawn up in workplaces were found to increase pharmacists' independent planning of their professional skills.
  • Mäkinen, Emilia (Helsingin yliopisto, 2021)
    Background and objectives: Documenting and processing of dispensing errors at both organizational and national levels is one of the basic preconditions for effective medication risk management. Since the most recently accomplished national register research of dispensing errors in Finland, there have been several changes in the medication dispensing process that advance medication safety. Thus, the previous study does not provide an up-to-date picture of the current situation. The primary objective of this study was to find out the trends in dispensing errors that were reported to the Finnish Pharmacy Association's registry of dispensing errors in 2015–2019. The secondary objective was to identify risk factors expository to dispensing errors in the dispensing process and to review the measures utilized by community pharmacies to prevent dispensing errors. Materials and methods: The retrospective registry study, in which the register of dispensing errors maintained by the Finnish Association of Pharmacists for the period from 1 January 2015 to 31 December 2019, was analyzed. Cases that did not fulfil the definition of a dispensing error (n=829) were removed from the original data (n=17763). In addition, clear errors (n=2130) were corrected in the data and cases (n=499) that were initially insufficiently entered in the register were added. 17433 dispensing errors were included in the study. The data was analyzed using Microsoft Excel. The number, qualities, prescription types, observers, therapeutic harms and contributory factors of the dispensing errors were investigated in the data. The most common groups of medicinal substance, high-alert medications and risk factors in the medication dispensing process were identified in the data. In addition, interventions reported by community pharmacies to prevent dispensing errors were collected from the data. Results: The number of cases reported to the dispensing error register has decreased annually (2015 n=3913, 2016 n=3795, 2017 n=3708, 2018 n=3578, 2019 n=2439). The most common types of dispensing errors are incorrect strength (51 % of all the reported dispensing errors) and incorrect quantity or package size (14 %). Slightly more than a half (51 %) of the reported dispensing errors were noticed by medicine users. The percentage of electronic prescriptions in dispensing errors has increased and is clearly the most common prescription type in dispensing errors (2015: 79 %, 2016: 84 %, 2017: 93 %, 2018: 96 %, 2019: 95 %). The majority of dispensing errors occurred with cardiovascular medicines (29 %) and medicines affecting the nervous system (26 %). 7 % of dispensing errors caused therapeutic harm to the medicine user. As a result of dispensing errors, 21 medicine users were hospitalized. 13 % of dispensing errors occurred with high-alert medications (n=2244). The high-alert medications were involved in one-third (n=7) of dispensing errors that led to hospitalization. Factors related to the employee (25 %), similar packaging (19 %), and similar medicine name (15%) were most commonly considered to be the main contributory factors for the occurrence of the dispensing errors. The risk factors identified in the medicine dispensing process were related to the pharmacy system, the characteristics of the prescription, the storage method of the medicine and the characteristics of the medicine packaging. In the automated dose dispensing process, the risk of dispensing error increased if changes had to be made to the dose dispensing order. The risk factors for automated dose dispensing were related to the pharmacy system and the characteristics of the prescription. The community pharmacies had mentioned taking measures to prevent dispensing errors in one-fifth (21 %) of the reported cases. In addition to developing their own operations, community pharmacies saw cooperation with other healthcare professionals as an important factor in preventing medication errors. In addition, community pharmacies reported exposing properties for dispensing errors of pharmaceutical products and systems to pharmaceutical companies and providers of pharmacy systems and automated dose dispensing. Conclusions: Trends, risk factors of the dispensing process and interventions to prevent dispensing errors can be identified in the dispensing errors reported to the Finnish Association of Pharmacists’ dispensing error registry. The dispensing error register provides valuable information on dispensing errors at the national level, but it is no longer able to fulfil completely the current medication safety needs. In the future, the role of the pharmacy as a promoter of medication safety should be perceived as more comprehensive. In the development of medication safety, special attention should be paid to the risk factors of the dispensing process, the high-alert medications and to new risks arising from the increase of electronic prescriptions and automated dose dispensing. In addition, cooperation between pharmacies and other healthcare professionals and the medication safety culture of pharmacies should be further strengthened.
  • Vilhunen, Noora (Helsingin yliopisto, 2021)
    Pharmacy compounding involves the preparation of customized medications that are not commercially available for individual patients with specialized medical needs. The compounded preparations have many special features, such as the rapid/immediate need for the drug, the preparation of several pharmaceutical dosage forms, and the variation of batch sizes and manufacturing processes. Medicinal products prepared in hospital pharmacies may pose additional risks to patients compared to industrial products. These risks with limited evidence of quality, efficacy and microbiological purity can jeopardize patient safety. The aim of this study was to perform a product specific risk assessment of aseptically processed and terminally sterilized products belonging to the manufacturing range of the hospital pharmacy of Turku University Central Hospital. The study material contained 118 different products. The risk assessment was performed with the help of a risk matrix in which various quality and safety risks have been identified and assessed. The risk points obtained from the different areas of risks were multiplied together to obtain total risk points for each product. The products were qualitatively classified according to the total risk points into low-risk, medium-risk and high-risk products. All total parenteral nutrition (TPN) solutions of the study were classified as high-risk products. TPN solution prepared into a syringe without lipids and TPN solution prepared into an EVA bag without lipids had the highest risk points of the study (6561 points). Most of the eye drops (88 %) and patient controlled analgesia (PCA) pumps (68%) belonged to high-risk category. PCA pump containing morphine, clonidine, bupivacaine, ketamine and saline solution (1944 points) and autologous serum eye drops (1296 points) had the highest risk points of these product types. 60 percent of intraocular injections and half of pain products prepared into syringes were scored as high-risk products. Intravitreal bevacizumab had the highest risk points of intraocular injections (972 points). Medium-risk products were mainly different infusions. Infusions containing defibrotide, oxytocin and onasemnogene abeparvovec had the highest risk points in the medium-risk category. Liquid solutions and patient controlled analgesia (PCA) pumps were the second largest group in this category. All products used in allergy testing, all ointments and all inhalation solutions were in the low-risk category. The risk matrix used in the study can be used to identify high-risk compounded preparations in hospital pharmacies. Risk assessment enables targeting quality assurance more effectively to high-risk products. Risk assessment can be used to manage various risks in pharmaceutical compounding and reduce harm to patients. The results obtained in the study cannot be directly generalized to other hospital pharmacies because the products, manufacturing processes and the amounts of different products prepared vary among hospital pharmacies.
  • Bahadori, Tadjmohammad (Helsingfors universitet, 2010)
    This master's thesis explored the activities of interpreters used by immigrants in Finnish health care. The main aim was to find out the actual roles of interpreters in working life and how these roles compare and contrast with the roles defined in interpreters` professional code of practice. Additionally, this study explored: what are the most important roles and competencies in the interpreters work from their own perspective and how they perceive their impartiality and proficiency. The interpreters` professional code of practice, Forsander`s (1996) study on interpreters roles and Jalbert`s (1998) classification of interpreter roles were used as a theoretical background of this study. Structured interviews were conducted among interpreters (n=32) working in metropolitan Helsinki. The interpreters were recruited from one interpretation center employing altogether 60 interpreters. The interview guide was based on a previous literature and included questions on interpreters work: their professional code of practice, roles, skills and competencies needed in working life. Interpreters perceived that the role of oral translator, cultural brokers and social role of the various expert institutions were the most important roles in their work. The least important roles were: the role of witnesses, counselor, and an additional source of information. The interpreters reported that they need special support and training in their work. This training should be organized conjointly both with native Finns and other cultures representatives. A shared understanding between different cultures can also be in focus in interpreter services. Similarly with previous studies, language and communication difficulties were found as a major challenge in Finnish health care. Interpreters highlighted that they customers are commonly dissatisfied with the health care due to a continuous rush and lack of time, and attitudes of health care personnel. Immigrants were satisfied with maternity clinic services and high level of technology applied in Finnish healthcare. Interpreters also mentioned that healthcare professionals` cultural skills and experiences are varying: the more they have experience of immigrants, the easier is communication. Interpreters perceived that the majority of healthcare professionals were positive to immigrants and were interested in developing their own cultural competencies. The roles reported by interpreters were in line with the roles defined in interpreters` professional code of practice. Additionally, the characteristics of a competent interpreter as mentioned in the code of practice were also perceived as important among interpreters. This research highlighted the need for cultural education among health care professionals.
  • Nieminen, Jenni (Helsingfors universitet, 2016)
    The aged are the biggest age group of using psychotropics. The most used ones of these drugs are hypnotic and sedatives that consists mainly of benzodiazepines and related drugs. However, the aged are extremely sensitive for these drugs that are also noted as potentially inappropriate drugs for the aged in the national, but also in the various international recommendations and care guidelines. Despite the care guidelines, benzodiazepine compounds are usually used for years and often concomitantly. Research material of this longitudinal, observational study with two cohorts was collected from structured interviews at two similar acute wards in Pori City Hospital during one month in 2015. The research protocol of an early similar study which was conducted in 2004 was followed. Results of the two studies (2004 and 2015) were compared. Interviews were conducted among patients aged ≥ 65 years. Users of benzodiazepines or related drugs (2004: n=38, 2015: n=32) were further interviewed. The aim of this study was to compare the characteristics of the usage of benzodiazepine compounds in the aged between the years 2004 and 2015. In particular the medicines information sources and amount of information on these drugs i.e. knowledge on adverse drug reactions was studied and compared. Additionally a systematic review was conducted to explore the current evidence on interventions to rationalize the use of benzodiazepines and related drugs in the aged. In 2004, 54% of the interviewed patients (n=64) were using benzodiazepine compounds. However, in 2015 there were 34% (n=36) using. In 2015 regular usage of these drugs was decreased and irregular usage (given on an as-needed basis) was increased compared to the year 2004. None of the patients used long-acting benzodiazepines in 2015. Medicines information is provided notably more by doctors and pharmacies to 2004, but still the information focused more on benefits of drug other than adverse drug reactions. However, the patients' knowledge about the adverse drug reactions of benzodiazepine compounds has increased. The patients got presented adverse drug reactions known on mean of five in the year 2015, while the same value in 2004 was three. In the both years, the most of the patients were aware of the dependence these drugs may cause. The usage of benzodiazepine and related drugs in the aged has become better, but there is still need to improve multi-professional cooperation and applicate new interventions for rationalize the usage of benzodiazepinecompounds.
  • Saarenpää, Maija (Helsingfors universitet, 2014)
    The body changes its response to medicine by age. Thus, medicines information for the elderly needs to differ from information targeted to younger adults. Package leaflets (PLs) are among the key sources of medicines information among general public. Although not generally recommended, benzodiazepines are commonly used by the elderly. The aim of this study was to evaluate the usability of benzodiazepine PLs and their information content from the elderly perspective. Additionally, the study aimed to explore how medicines information targeted to elderly in PLs aligns with the information targeted to health care professionals (HCPs). The study focused on PLs of benzodiazepines and their derivatives (diazepam, alprazolam, oxazepam, zopiclone and temazepam) that are commonly used but not recommended for the elderly. The usability of PLs was evaluated by using the Medication Information Design Assessment Scale (MIDAS). The informational content of PLs was studied by identifying all references for the elderly and comparing them to information targeted to HCPs in Database of medication for the elderly, Beer's criteria, Kapseli 35 publication, Martindale, Current Care Guideline for insomnia and the Summaries of Product Characteristics. The usability of the PLs in this study required several improvements. The mean of MIDAS-credits was 6,22 (n = 27; range 5,00-7,00), the scale maximum being 13. Sufficient line spacing and highlighting of important information were among the poorly represented elements. The occurrence of different font-sizes also varied. The most proficiently represented features included headings, contrast and the usage of upper and lower case in text. The PLs included in the content-analysis contained references to the elderly in all cases except one (n = 35). The references were categorized to general warnings, side effects and dose recommendations. They were in line with the information targeted to HCPs, but relatively short and often inadequate. Most PLs did not give an adequate overall picture of the medicine use among the elderly. The PLs for benzodiazepines need to be improved from the elderly perspective both in terms of information content and usability. Attention both from the medicine authorities and the pharmaceutical industry is required. Alternatively, separate drug-specific information leaflets for the elderly may be developed.
  • Falck, Jenni (Helsingfors universitet, 2019)
    Biological medicines are gaining ground in drug therapy. However, biological medicines are considerably expensive. Top ten drugs that caused the most drug reimbursement expenses included six biological drugs in Finland in 2017. A biosimilar is a biological medicine which is highly similar to another biological medicine (the reference medicine) that has already approved. Biosimilar prices are cheaper than the original medicines because their clinical development program does not have to be as extensive. A wide use of biosimilars save costs for both the patient and society without changing the effectiveness of drug therapy. The aim of this study is to investigate the automatic substitution of biological drugs containing the same active ingredient, especially from the point of view of medication safety. The study was conducted as a systematic literature review. Literature search was carried out by using Pubmed and Scopus databases. The literature was also searched manually from references of the articles and from the industry experts. The literature search produced a total of 454 articles after the deletion of duplicates. A title, abstract and full text screening was conducted by two independent researchers. All in all, 65 articles met the inclusion criteria of the study. As no studies were found on the automatic substitution of biological medicines from the point of view of medication safety, it was decided to include in the study original studies investigating the substitution of biological drugs from the point of view of doctors (n=8), pharmacists (n=3), patients (n=1) and various stakeholders (n=2). The original studies were all surveys except one study. In addition, the review included statements of various medical associations and organizations (n=23), descriptive reviews (n=27), and expert views (n=2) on the automatic substitution of biological drugs. According to the results of the original studies (n=13), it can be stated that automatic substitution is not considered generally acceptable. Doctors consider it is very important that the pharmacist informs them if substitution occurs. They also think it’s critical that doctors should be able to prevent substitution. Patients are also sceptical about the substitution of biological drugs. The quality of the original studies was assessed by the generalizability of the research results. The generalizability of the results of the original studies is weak due to the methodological shortcomings of the studies. Although the automatic substitution of biological drugs is legal in some countries, such as in France and in Australia, it has not been studied from the point of view of medication safety. In order to be safe to implement automatic substitution of biological medicines, more should be investigated on the subject. From the point of view of medication safety, healthcare professionals and patients will need further target group education on biosimilars. In addition, it should be clarified what kind of education the healthcare professionals and patients would need if the automatic substitution of biological medicines was to be realized.
  • Teittinen, Panu (Helsingfors universitet, 2017)
    Psoriasis (Ps) and Psoriatic Arthritis (PsA) are chronic inflammatory diseases that are associated with profoundly impaired quality of life. Psoriasis is incurable and therefore the treatment aims to relieve patient's symptoms and improve the quality of life. Biologics are an efficacious treatment option for moderate-to-severe Ps and PsA but their relatively high costs limit their use. Health care resources are scarce and therefore economic evaluations provide crucial information for decision-makers. The objectives of this study was to determine 1) What is the incremental cost-effectiveness of biologics for moderate-to-severe Ps and PsA, and 2) What is the quality of cost-utility analyzes examining the subject. The theory section of this Master's thesis considers the current treatment alternatives for Ps and PsA and costs relating their use. The main principles and methodologies conducting economic evaluation and systematic review are also discussed in the theory section. The empirical section concerns the previous systematic reviews regarding the cost-effectiveness of biologics for the treatment of moderate-to-severe Ps and PsA, while also addressing the results of this systematic review and the quality of included cost-utility analyzes. 1425 references were found with the systematic literature search and 17 of them were included in this study. Eight articles concerned the cost-effectiveness of biologics for the treatment of Ps and nine articles for the treatment of PsA. All of the included studies used cost-utility modelling approach. Based on the results of this systematic review, biologics are cost-effective compared standard care for the treatment of severe Ps. Biologics are also cost-effective compared to the standard care for the treatment of moderate-to-severe PsA. However, future studies, independent of influence of pharmaceutical industry, are needed to confirm these results. The quality of cost-utility analyzes included in this study varied substantially. The main shortcomings related to reporting of the data included, modelling methodologies and the arguments for choosing the treatments compared. The strengths of this study are a comprehensive and systematic literature search, careful evaluation of included data and the transparency of methodologies. The main weaknesses relate to generalizability of the results and the possibility of biases. This study updates the current knowledge of cost-effectiveness of biologics for Ps and PsA, while providing a good foundation for the future studies to be conducted.
  • Joensuu, Jaana (Helsingfors universitet, 2013)
    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.
  • Mäkinen, Arttu (Helsingfors universitet, 2018)
    This is a systematic review aiming to investigate the efficacy, effectiveness, and safety of biosimilars in the treatment of inflammatory bowel diseases. Biosimilar drugs used to treat inflammatory bowel diseases include biosimilar infliximab and biosimilar adalimumab. Biosimilar infliximab has been authorized by the European Medicines Agency (EMA) in 2013 and by the US Food and Drug Administration (FDA) in 2016. Biosimilar adalimumab has been authorized by EMA and FDA in 2017 and, at the time the literary search for this systematic review was conducted no studies were found regarding the treatment of adalimumab biosimilar for inflammatory bowel diseases. To acquire marketing authorization for biosimilars, it must be proven that the biosimilar is biologically similar to the original medicinal product. Bioequivalence is demonstrated through physicochemical trials and clinical trials. However, clinical trials do not have to be performed with all of the indications for which the original medical product is registered. After proving bioequivalence with one or more indication it is possible to extrapolate the biosimilar to be used in all of the original medical products indications. This has raised the question of whether biosimilars are really comparable to the originator in indications for which no clinical trials have been conducted. This systematic review was implemented using the Cochrane Handbook for Systematic Reviews and Interventions. Systematic literature searches were made in Cochrane, Medline (Ovid®), PubMed and Scopus databases on 12.05.2017. 14 observational studies, one systematic review and a randomized clinical trial that met the inclusion criteria were included in the systematic review. The quality of the publications was evaluated using the STROBE-, NOS- and CONSORT-checklists and information regarding the efficacy, effectiveness and safety of biosimilars was extracted. CD-patients receiving tumor necrosis factor alpha inhibitors for the first time, the clinical response was achieved in 50.0 % to 97.2 % of patients depending on patient population and the duration of treatment. Similarly, for UC-patients, the clinical response was achieved in 62.2 % to 100.0 %. The clinical remission was achieved among 28.9 % to 84.4 % of CD-patients and among 28.9 % to 84.4 % of UC-patients, depending on patient population and treatment follow-up. After the switch from original infliximab to biosimilar, the proportion of patients in clinical remission during follow-up ranged from 62.3 % to 100.0 % in CD-patients and from 45.5 % to 100.0 % in UC-patients. Clinical remission was sustained throughout the whole follow-up in 70 % to 100 % of CD-patients and 66.7 % to 92.0 % of UC-patients. The incidence of adverse events leading to the discontinuation of drug treatment was between 0.0 % and 25.0 %, and the incidence of all adverse events ranged from 0.0 % to 93.6 % in CD- and UC-patients. Biosimilar infliximab seems to be comparable to the original product regarding the efficacy, effectiveness and safety. This result is supported by the systematic literature review published earlier. Conducting a meta-analysis of the information contained in this systematic literature review could have led to a more final decision considering efficacy, effectiveness and safety of biosimilar-infliximab in the treatment of inflammatory bowel diseases.
  • Luukkanen, Saana (Helsingin yliopisto, 2021)
    Pharmaceutical costs have been rising globally every year. A significant portion of drug costs is caused by biological drugs, which are often very expensive, yet essential in the treatment of many chronic diseases. Biosimilars are clinically equivalent to biological originator products and are expected to alleviate the increase in drug costs. The biosimilar development process does not need to repeat the complete development process of the originator product, allowing the biosimilar to enter the market at a lower price than the originator after the patent and data protection period for the originator ends. The aim of this study was to find out what impact the market entry of biosimilars has on the prices of the reference products in outpatient care in Finland, and to investigate whether biosimilars create price competition for biological drugs. In addition, the study examined how the prices and market shares of outpatient biosimilars have developed in Finland. The study examined the development of price and market shares for adalimumab, etanercept, insulin glargine, insulin lispro, enoxaparin, filgrastim, pegfilgrastim, somatropin, follitropin alfa, teriparatide and epoetin biosimilars and their reference products. The data for the study was acquired from IQVIA and it covered pharmacy wholesale data between 1.1.2009–31.8.2020 for products under investigation. The weighted average wholesale price and monthly wholesale amounts were determined for each product, and the development of the price and market shares were analyzed. In addition, a linear segmented regression analysis was performed to examine the impacts of market entry of biosimilars on the prices of the reference products. According to the study, the prices of the reference products mainly decreased after the biosimilar entered the market. If the price of the reference product did not fall, it lost its reimbursement under the Health Insurance Act. The market shares of the reference products were marginal when they were no longer reimbursed. The prices of biosimilars did not change as much as the prices of reference products, and for most active substances biosimilar prices remained stable or decreased. The use of biosimilars varies widely between different biologics. The study found that prices of reference products were decreasing mainly as a result of various changes in drug policies. Therefore, biosimilars were not seen to generate genuine price competition between biological products. In many of the drug groups examined, the market shares of biosimilars had future growth potential.
  • Backman, Heidi (Helsingin yliopisto, 2020)
    Theoretical framework: The consolidated pharmaceutical market is becoming increasingly global and the same international pharmaceutical companies operate around the world in different countries, responsible for drug development and production. The high costs of developing novel medicines and the motive for higher profits has led to elevating price level of pharmaceuticals and health care services. Finland and the U.S. offer two extremes at the pharmaceutical market. The pharmaceutical market field in Finland is very structural and rigid, and medicine prices are regulated by law. In the U.S. the prices are based on the laws of supply and demand and the prices differ by different states, retailers and insurance policies. A small-scale longitudal price comparison is also reviewed to showcase the effect of continuously rising medicine prices. Study objective: The idea of this study is to describe and compare pricing mechanisms of pharmaceuticals and price differences between two very different market structures and review how these might affect the cost-effectiveness of national health care spending. These divergences are also mirrored to survey recent global pharmaceutical market problems such as drug shortages, possibly due to less appealing markets of higher price regulation policies. Materials and methods: Price data were collected from national, official, open-source databases. National health care expenditure and comparison to GDP was collected from publications by the OECD. All monetary values have been presented in both currencies (EUR and USD) to present more comparable values. Results: When compared to other OECD-countries the U.S. spent distinctly the largest amount of funds on health care per capita. Finland’s national health care costs were thousand times minor in total spending and less than a half per capita when compared to those of the U.S. With lower expenditure Finland manages to offer access to public, government-funded health insurance program. Meanwhile the prices of prescription medicines in Finland have decreased significantly, the prices for have continuously elevated in the U.S. Conclusions: The outcome of this study is that free markets and a complex supply chain, compared to more regulated markets with more transparency, have higher overall price level in pharmaceuticals and health care services. Free markets and sufficient intellectual property rights are more enticing to pharmaceutical companies. They promote new innovations and developing of much-needed novel therapies to modern health problems, such as AIDS and the global threat of worsening situation of antibiotic resistance. More regulated markets may create problems such as drug shortages and are often considered complex and less appealing market systems due to high level of administrative work but conserve the cost-effectiveness of the use of public funds.
  • Tyyskä, Miia (Helsingfors universitet, 2009)
    Diabeetikoiden määrä lisääntyy jatkuvasti. Samalla hoitokulut ovat kasvaneet merkittävästi. Paras tapa hillitä kustannusten kasvua on hoitaa diabetesta mahdollisimman hyvin. Näin voidaan ehkäistä myös diabetekseen liittyvien oheissairauksien syntyä. Diabeteksen hoidossa on tärkeää kiinnittää huomiota hoidon jatkuvuuteen ja potilaan hoitoon sitoutumiseen. Apteekin henkilökunnan asema on noussut yhä keskeisemmäksi diabeetikon hoitoon sitoutumisen edistäjänä. Tämän pro gradu -tutkielman tavoitteena oli selvittää, mikä on apteekin farmaseuttisen henkilökunnan rooli diabetespotilaan hoitoon sitouttamisessa, elämäntapamuutosten toteuttamisessa ja niiden pysyvyyden varmistamisessa. Asiaa tarkasteltiin voimaantumisen teorian näkökulmasta. Tarkoituksena oli selvittää, miten voimaantuminen yksilössä tapahtuu, miten sitä voidaan apteekkineuvonnalla edistää ja mikä on apteekin rooli ulkopuolisena voimaannuttajana. Tämän tutkimuksen aineisto on kerätty Mäntyharjun Havu apteekissa ja se on osa laajempaa tutkimusta, jonka päätavoitteena on kehittää ja testata apteekkeihin soveltuva yksilökeskeinen toimintamalli tyypin 2 diabeteksen hoidon tukemiseen. Toimintamalli perustuu säännöllisiin neuvontatapaamisiin apteekissa. Pro gradu -tutkielmaan analysoitavaksi valittiin tutkimusjoukosta (n=19) ne, joilla tapahtui apteekkiohjelman aikana eniten positiivisia muutoksia yksilötasolla sekä elämäntapamittareilla mitatuissa arvoissa että kliinisissä parametreissa (n=4). Kvaliatiivisessa analyysissä käytettiin sekä deduktiivista että induktiivista lähestymistapaa. Vaikka diabeetikoilla oli tietoa sairaudesta ja elämäntapojen merkityksestä, niin käytännön tasolla jokainen henkilö kaipasi hoitoon ja erityisesti muutosten toteuttamiseen tukea ulkopuoliselta taholta. Apteekin rooli ulkopuolisena voimaannuttajana koettiin erityisen keskeiseksi. Tapaamiset loivat oikeanlaisen ympäristön ja ilmapiirin elämäntapamuutosten toteuttamiseen ja voimaantumisprosessin etenemiseen. Voimaantuminen ruokavaliomuutoksiin oli koko intervention aikana melko nousujohteinen prosessi. Sen sijaan voimaantuminen liikunnalliseen elämäntapaan oli aaltoilevaa. Apteekkitapaamiset sosiaalisena tapahtumana paransivat asiakkaan hoitoon sitoutumista. Asiakas koki, että häntä kohdellaan yksilönä kokonaisvaltaisesti. Voimaantuakseen yksilö tarvitsi aikaa. Vuoden mittaisen intervention aikana voitiin saavuttaa pysyviä muutoksia elämäntapoihin, mikäli yksilöllä itsellään oli halu ja motivaatio sitoutua tukiohjelmaan. Tämä tutkimus osoitti, että tämänkaltaista apteekkiohjelmaa tarvitaan. Nykyisessä kiireyhteiskunnassa ihmiset arvostavat, jos jollakin on aikaa paneutua yksilöön itseensä ja hänen sairautensa hoitoon kokonaisvaltaisesti.
  • Vainio, Sanna (Helsingfors universitet, 2019)
    Despite the long history of skin grafting, there is no standardized treatment for split-thickness skin graft donor sites. These sites cause a notable amount of pain and discomfort to the patients and open wounds also introduce a risk for infection. There is an extensive need for treatment options promoting the fastest and least painful healing possible while also being infection-free. The treatment of split-thickness skin graft donor sites is constantly studied and there is plenty of scientific literature available about this topic. In the theory section of this Master’s thesis, the structure of skin, the process of wound healing, skin grafting surgery and wound care products for split-thickness skin graft donor sites are briefly introduced. Additionally, the method of systematic review is described. In the empirical section, a systematic review is performed to compare animal- and non-animal-based wound care products in the treatment of split skin graft donor sites. The methodological quality of the included studies is reviewed. In the literature search, 3552 references were found. In this systematic review a total of 23 articles were included comprising of 21 comparative clinical studies and two previous literature reviews. Of the original studies, 20 reviewed healing, 14 infection and 17 pain of the split-thickness skin graft donor sites. Based on the results of the systematic review, animal-based wound care products might promote healing and reduce pain experienced by patients in the treatment of split-thickness skin graft donor sites when compared with non-animal-based wound care products. The results concerning infection were inconsistent. Generally, the reporting of the clinical original studies was not comprehensive enough for proper evaluation of methodological quality. Some defects, mostly in the blinding of the patients, study personnel and the assessors of outcomes, were also found. Moreover, the studies were heterogeneous in their definitions and measuring of the reported outcomes. Therefore, there is substantial uncertainty in the results of this systematic review. The systematic and transparent way of conducting the literature search, the review of the methodological quality and the reporting of the outcomes can be considered as a strength of this thesis. The main weakness is, that only one person performed the critical steps of this study, which might increase the risk of bias and reduce the repeatability of the study.
  • Rissanen, Johanna (Helsingin yliopisto, 2020)
    Lääkevaihto ja sitä täydentävä viitehintajärjestelmä ovat laskeneet lääkekustannuksia Suomessa. Epilepsialääkkeet eivät ole aiemmin kuuluneet lääkevaihdon piiriin, sillä epilepsian hoidossa eri valmisteet eivät välttämättä ole terapeuttisesti tarpeeksi samanarvoisia, ja pienikin muutos hoitotasapainossa voi altistaa epilepsiakohtauksille. Nykyisin epilepsialääkkeitä käytetään kuitenkin usein muihinkin käyttöaiheisiin, kuten psykiatrisiin sairauksiin ja kivun hoitoon. Vuonna 2017 lääkekorvausjärjestelmään tehtiin säästötoimenpiteitä, joiden yhteydessä epilepsialääkkeet sisällytettiin lääkevaihdon piiriin muissa käyttöaiheissa kuin epilepsian hoidossa. Lisäksi otettiin käyttöön poikkeava viitehintaryhmä, joka koski epilepsialääkkeistä pregabaliinia neuropaattisen kivun käyttöaiheessa. Tutkimuksen tavoitteena oli tarkastella epilepsialääkkeiden (pregabaliinin, gabapentiinin, topiramaatin, lamotrigiinin ja valproiinihapon) vaihtamista sekä hintojen kehitystä lääkevaihtoon ja viitehintajärjestelmään sisällyttämisen jälkeen vuoden 2017 alusta vuoden 2019 puoliväliin. Lisäksi tarkasteltiin näiden lääkeaineiden kustannusten, korvausmenojen sekä käyttäjä- ja reseptimäärien kehitystä. Aineistona käytettiin Kansaneläkelaitoksen reseptirekisteriin pohjautuvia tilastoja epilepsialääkkeiden lääkeostoista sekä lääkkeiden hintalautakunnan päätöksiä epilepsialääkkeiden viitehintaryhmistä ja viitehinnoista. Epilepsialääkkeiden vaihtaminen yleistyi tarkastelujakson aikana kaikilla lääkevaihdon piirissä olleilla viidellä lääkeaineella, ja vaihtokieltojen osuus resepteistä laski useimmilla lääkeaineista. Viitehinnat laskivat useimmissa tarkastelluista viitehintaryhmistä, mutta lähes yhtä usein viitehinta ei muuttunut. Viitehinnat laskivat enemmän viitehintaryhmissä, joissa oli useampia vaihtokelpoisia valmisteita. Lääkevaihdon ensimmäisenä vuonna 2017 lääkevaihtoon kuuluvien epilepsialääkkeiden kustannukset ja korvausmenot pääosin laskivat, vaikka lääkkeiden käyttö ei vähentynyt. Lääkevaihdon toisena vuonna kustannukset eivät juuri laskeneet. Pregabaliinin poikkeavan viitehintaryhmän vuoksi vaihtamatta jääneet reseptit aiheuttivat merkittävän osan lääkevaihtoon kuuluvien epilepsialääkkeiden kustannuksista. Pregabaliinille jäi siten todennäköisesti yhä säästöpotentiaalia poikkeavan viitehintaryhmän voimassaolon päätyttyä vuoden 2019 heinäkuussa, mitä on syytä tarkastella jatkotutkimuksissa.