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Yhteiskunnan digitalisaatio on lisännyt verkkopalveluiden käyttöä monilla aloilla, ja suurin osa suomalaisista käyttää internetiä esimerkiksi palveluiden tai tuotteiden hankintaan. Erilaisten digitaalisten terveyspalveluiden käyttö on kasvanut viime vuosina, ja koronapandemia on nopeuttanut muutosta. Suomessa useat apteekit ovat perustaneet viime vuosina verkkopalveluita, mutta niiden käyttö on ollut edelleen vähäistä. Tämän tutkimuksen tavoitteena oli tutkia koronapandemian vaikutuksia Yliopiston Apteekin (YA) verkkopalvelun käyttöön. Tutkimuksessa tutkittiin rekisteriaineistojen perusteella kokonais- ja reseptiasiakasmäärän sekä reseptimäärän ja asiakasprofiilin muutosta ennen koronapandemiaa ja sen aikana vuosina 2018-2020. Lisäksi tutkittiin YA:n Lääkeneuvonta- ja asiakaspalveluyksikön (Tiepa) vastaanottamien puhelin- ja chat-yhteydenottojen määrää ja sisältöä sekä kyselyaineiston perusteella apteekin verkkopalvelun käyttäjien näkemyksiä koronapandemian vaikutuksista heidän apteekin verkkopalvelun käyttöön. Monimenetelmätutkimuksessa tutkittiin apteekin verkkopalvelussa tapahtunutta muutosta apteekin asiakas- ja myyntitietojen sekä asiakaskyselyn avulla. Tutkimuksessa hyödynnettiin YA:n myynti-, asiakas-, Tiepa- ja pikanoutorekisteriaineistoja sekä YA:n toteuttaman ’’Verkkoapteekki 2020’’ -kyselytutkimuksen aineistoa. Aineistot analysoitiin kvantitatiivisesti Microsoft Excel (16.0) ja IBM SPSS (26) ja R (4.0.3) tilasto-ohjelmistoilla. Myyntiä tai asiakasmääriä mittaavia aineistoja analysoitiin indeksin pisteluvuilla. Kokonais- ja reseptiasiakasmäärälle sekä reseptiasiakkaille keskimäärin toimitettujen reseptien lukumäärälle laskettiin myös tilastollinen merkitsevyys lineaarisella regressioanalyysillä 95 % luottamusvälein. Kyselytutkimuksen lopputulosmuuttujista tehtiin kuvaileva tilastoanalyysi frekvenssijakaumien ja prosenttiosuuksien avulla. YA:n verkkopalvelun käyttö lisääntyi merkittävästi tarkastelujaksolla 2018 – 2020. Kokonais- ja reseptiasiakasmäärän muutokset koronapandemian aikana olivat tilastollisesti merkitseviä. Pandemian vaikutus verkkopalvelussa vastasi pandemiaa edeltävän lineaarisen kehityksen perusteella kokonaisasiakasmäärässä 6 kuukauden ja reseptiasiakasmäärässä yli 3 vuoden kehitystä. Apteekin verkkopalvelun käyttö ja tiettyjen koronasairauden hoitoon median mukaan soveltuvien valmisteiden myynnit lisääntyivät merkittävästi kevään 2020 aikana. Tiepan chat-palvelua käytettiin paljon terveyteen ja hyvinvointiin liittyvien kysymysten selvittämiseen. Koronapandemia lisäsi erityisesti iäkkäämpien asiakkaiden (yli 55- ja erityisesti yli 65-vuotiaiden) apteekin verkkopalvelun käyttöä. Infektioriskin vähentäminen oli tärkeä syy apteekin verkkopalvelun käyttöön. Vuoden 2020 aikana apteekin verkkopalvelussa tapahtui digiloikka. Koronapandemia lisäsi merkittävästi ja tilastollisesti merkitsevästi apteekin verkkopalvelun käyttöä ja toi sen uusiksi käyttäjiksi myös iäkkäämpiä asiakkaita. Erityisesti reseptilääkkeiden hankinta apteekin verkkopalvelusta lisääntyi. Tiepa oli tärkeä tietolähde ennen koronapandemiaa ja sen aikana. Pandemia-aikana luotettavan lääkeinformaation tarve korostuu. Jatkotutkimuksissa on tärkeä tutkia apteekin verkkopalvelun käytön ja asiakasryhmien muutoksia sekä asiakkaiden kokemuksia verkkopalvelusta osana YA:n monikanavaista apteekkipalvelua.

Pharmacotherapy plays a key role in the treatment of many conditions. Long-term medication therapy is an essential part of treatment in many common chronic conditions in Finland, such as diabetes, asthma, and cardiovascular diseases. However, medication therapy can be burdensome to patients and thus, influence their functional capacity and well-being. Therefore, patients’ lived experience of medication and its effect on their lives has a growing interest as a research area. The primary aim of this study was to test among Finnish patients with chronic conditions the consistency of a theoretical model ‘Patient’s Lived Experience with Medicine’ (PLEM) developed by a qualitative meta-synthesis by Mohammed et al. (2016). The secondary aim was to investigate the medication-related burden experienced by Finnish patients living with different chronic conditions. Based on the results of the content analysis of the focus group discussions, this study aimed to create a new, concise measure of medication-related burden to be utilized in a population-based online survey on medication use in Finland called Medicine Barometer (Lääkebarometri) by the Finnish Medicines Agency Fimea. The study was conducted as a qualitative focus group interview in summer 2020. Participated patients with chronic conditions (n=14) were recruited through four patient organizations. Focus group discussions (n=5) were held in groups of 2-3 people over Zoom. Deductive content analysis guided by PLEM model was used for data analysis. The measure of medication-related burden was formed on the grounds of the original PLEM model, content analysis of the interviews, research literature and expertise of the research group. The results of the focus group discussions (n=5) supported the functionality of the PLEM model. Study participants (n=14) described similar experiences of medication-related burden and beliefs and practices guiding the medication taking to those presented in the PLEM model. Burden caused by medication routines and healthcare system were most emphasized of the factors contributing to medication-related burden. As a new factor contributing to the burden, medication-related eco-anxiety emerged. The new measure for assessing medication-related burden consists of 13 items to be piloted by the Finnish Medicines Agency Fimea in the summer 2021. The experiences of the Finnish patients with chronic conditions are consistent with the PLEM model. Majority of the participants did not experience such burden from their medication that would significantly interfere with their daily lives. However, experiencing higher level of medication-related burden appeared to be related to independently modifying medication regimen or even neglecting the use of medicines. PLEM model and related patient interviews served as a solid foundation for developing items for the new measure to be piloted for assessing medication-related burden. The population-based survey will provide useful data for the further development of the measure and for researching the factors contributing to the burden.

Medication reviews have been highlighted as one of the most important strategies for improving medication safety and medication management especially in older adults. Current electronic health records document and communicate e-prescriptions but their medication use related patient information content should be extended to cover e.g. medication review documentation. The documentation should be in structured format to be useful in clinical practice and evidence-informed decision-making. The aim of this study was to identify medication review related patient information and other patient data that should be in a structured form in electronic health record systems (EHRs) at a national and organizational level. The aim was also to determine which medication review related patient information should be documented in electronic health record systems. The study was conducted as 3-round survey using the Delphi-method. The Delphi method is a qualitative consensus method based on the views of experts aiming at reaching consensus of the experts on the studied subject. The Delphi rounds were conducted as electronic surveys in September-December 2020. Expert panelists assessed which medication-related patient data and other data generated by healthcare providers should be documented in a structured form in EHRs and in which national digital data system services (Kanta and My Kanta Pages) the medication review related patient information should be accessible and by whom. The expert panel consisted of 41 participants: 12 physicians, 13 pharmacists, 10 nurses, and 6 information management professionals. The results of the study were analyzed both quantitatively and qualitatively. Consensus was reached on a total of 108 medication review related patient information topics that should be documented in a structured form in EHRs and that should be available for medication reviews through EHRs. Of the topics, 39 related to medication reviews in general, 25 to adverse drug reaction symptoms, 11 to the burden of adverse drug effects, 12 to laboratory tests and other test results, 12 to medication adherence and 9 to the use of intoxicants. Structuring the data was considered as important or important to some extent in most of the presented medication review related information topics. Especially, the documentation of renal function was rated by the expert panelists as a crucial piece of information to be structured. Medication adherence information and information related to the use of intoxicants were rated as less important to be documented in a structured form than other topics. Consensus was also reached on the accessibility of medication review documentation in the Kanta and My Kanta services. The expert panel of this study had a common and strong view that data related to medication reviews should be structured in EHRs. The expert panel reached a strong consensus that almost all of the data presented in the study should be structured. Based on this Delphi study, the expert panel identified the benefits of structuring and standardized recording. Because not all data can be structured at once, further prioritization of the data identified in this study is still needed. The practical implementation of the structured information could be accomplished in the form of a checklist. The study addresses a very current problem related to the shortcomings of medication information management and overall medication management.

Iäkkäiden määrän lisääntyminen aiheuttaa tarpeen kehittää ja tutkia uusia lääkkeitä sekä lääkemuotoja entistä enemmän. Iän tuomat fysiologiset muutokset sekä useat sairaudet voivat aiheuttaa ongelmia perinteisten lääkkeiden annostelussa. Annosteluongelmien ratkaiseminen lääkemuodon muokkaamisella voi kuitenkin aiheuttaa riskin lääkitysturvallisuudelle. Tämän pro gradu -tutkielman tarkoituksena oli tutkia iäkkäitä potilaita hoitavien lääkäreiden kohtaamia lääkemuotoihin liittyviä ongelmia. Tutkimuksen avulla pyrittiin selvittämään, kohtaavatko lääkärit hoitotyössä lääkemuotojen aiheuttamia ongelmia, ja minkälaisia ongelmia lääkärit kohtaavat. Lisäksi lääkäreiden haastatteluissa esiinnousseita teemoja verrattiin hoitajien kolmen päivän seurantajakson aikana verkkokyselylomakkeelle kirjaamiin lääkemuotoihin liittyviin käytännön ongelmiin, joita käytännön hoitotyössä palveluasumisen yksiköissä ilmeni aiemmin toteutetussa tutkimuksessa. Tutkimuksessa haastateltiin viittä lääkäriä, joilla oli kokemusta iäkkäiden lääkehoidosta. Lääkärit etsittiin tutkimukseen mukaan sosiaalisen median kautta hakuilmoituksella. Puolistrukturoidut haastattelut nauhoitettiin ja litteroinnin jälkeen niiden analysoinnissa käytettiin aineistolähtöistä sisällönanalyysiä. Tabletteihin liittyviksi ongelmiksi lääkärit mainitsivat niiden ison koon ja pintaominaisuudet, joiden vuoksi niiden nieleminen vaikeutuu. Muita ongelmia olivat tablettien tunnistettavuus, jakouurteen puute sekä sopivien vahvuuksien puute, vaikkakin yleisesti lääkäreiden mielestä eri vahvuuksia on tarpeeksi markkinoilla. Kapseleiden ongelmiksi lääkärit mainitsivat myös ison koon sekä epäselvyyden siitä, saako kapselia avata vai ei. Oraaliliuosten ongelmiksi koettiin paha maku, liian laimeat vahvuudet, lasku- ja mittaamisvirheen riski sekä sekaantumisen vaara. Lääkelaastarit jakoivat mielipiteitä, mutta niiden ongelmiksi lueteltiin muun muassa iho-oireet ja laastarin irtoaminen. Yleisesti lääkärit eivät olleet tablettien murskaamisen kannalla, mutta jokainen haastatelluista lääkäreistä totesi murskaamisen olevan joissakin tilanteissa ainoa vaihtoehto. Lisäksi lääkärit luettelivat useita lääkemuotoihin liittymättömiä ongelmia, jotka liittyivät sekä potilaaseen mutta myös terveydenhuoltojärjestelmään. Jotta lääkemuotoihin liittyviä ongelmia voitaisiin vähentää, tulisi iäkkäiden kohdalla aina arvioida lääkehoito säännöllisesti. Arvioinnin perusteella iäkkäälle voitaisiin valita hänelle parhaiten sopivat lääkemuodot ja huolehtia siitä, ettei tarpeettomia valmisteita ole käytössä. Lääketeollisuuden ja lääkeviranomaisten vastuulla on edistää lääkkeiden kehitystä ja uusien innovaatioiden tuomista markkinoille. Käytännössä lääketeollisuus voi helpottaa terveydenhuollon ammattilaisten työtä tuottamalla selkeitä lääkeinformaatiotekstejä, joilla voisi esimerkiksi helpottaa murskaamispäätöksen tekemistä.

The objective of this research has been to investigate the management of alerts of Medicines Verification Systems in Europe. Verification of medicines according to Falsified Medicines Directive (FMD) came into force 9.2.2019. There is no standardized tool or system for the management of alerts, every Medicines Verification Organisation and manufacturer have had to find their own ways to manage the alerts. The research has been performed as a theme survey via questionnaire that has been sent to Medicines Verification Organisations in 30 European countries. Information to the questions of the questionnaire has also been gathered from the Internet pages that are mainly maintained by the Medicines Verification Organisations. This kind of method triangulation has been used in order to improve the reliability of the research. Answering rate of the survey was 17 %. By including the information gathered by method triangulation the overall yield percent of information in this study was 45 %. The information received via the questionnaire did not contradict with the public information. As conclusion, marketing authorization holders have been registered as users of the National Medicines Verification Systems or they have signed a contract with Medicines Verification Organisations. Marketing authorization holders are paying the costs of the Medicines Verification Systems. Penalties of FMD non-compliance are in use in part of the European countries. In the beginning of the implementation of the Medicines Verification System there has been stabilization periods in use which have already ended in half of the European countries. National competent authority is informed about system alerts typically in case of suspected falsification. In half of the European countries there is a separate computerized alert management system in use. Marketing authorization holder usually has access to the system. In some of the countries it is possible to integrate the system to the own serialization system of the marketing authorization holder. In six European countries there has been set a specific time for the alert investigation of the marketing authorization holder. Based on the results of this research the alert management system that covers the whole Europe that European Medicines Verification Organization is planning would really be needed. One common computerized system and common rules would ease up the alert management of all the stakeholders of the medicines verification.

The Finnish medicine reimbursement system is complex and several different conditions required by the Health Insurance Act (1224/2004) and the Social Insurance Institution of Finland (Kela) must be met in order to receive medicine reimbursement. The understanding of medicine reimbursement criteria from the perspective of medicine users has not been studied in Finland before, and little research has been done on the subject internationally. Medicine user-oriented research on the medicine reimbursement system, both in Finland and internationally, has largely focused on the financial opportunities of medicine users to purchase medicines and their opinions on the fairness of medicine reimbursements. The aim of this study was to obtain information on the understanding of medicine reimbursement criteria and the background factors affecting it, the implementation of price, generic substitution and medicine reimbursement counselling in pharmacies, seeking advice on medicine reimbursement, and the financial difficulties of buying prescription medicines. The material used in this study was from the population survey (n=1650), which examined the activation of price competition for pharmaceutical products and customers' expectations of pharmacy operations. The understanding of medicine reimbursement criteria, the price counselling provided in a pharmacy, the effect of financial challenges on the non-buying of medicines and the use of sources of advice related to the medicine reimbursement were described as frequency distributions. The effect of background factors on the understanding of medicine reimbursement criteria was compared using the chi-square test and logistic regression analysis. About a third (31%) of respondents told that they do not understand the basis on which medicine reimbursement is usually received for prescription medicines, and 13% had unclear why they had not been reimbursed for their prescription medicine in the past year. Especially younger age, low income, low medication use, depression and other mental health problems, lack of long-term illness, and insufficient medicine reimbursement counselling in a pharmacy were found to be associated with poorer understanding of medicine reimbursement. 72% of the participants in the study felt that they usually receive sufficient information about the prices of medicines and 61% about the reimbursement of medicines when buying prescription medicines from a pharmacy. Less than half (47%) of respondents felt that they have usually received sufficient information about how the amount of reimbursement for medicines is determined. Slightly over 70% of respondents said that they are usually told about the cheapest medicine available when buying a prescription medicine and/or are suggested to switch to a cheaper one. About 60% were usually told about the difference between the two interchangeable medicines. 88% of respondents would seek information about medicine reimbursement primarily from a pharmacy or pharmacy´s online services. About 3% of all respondents in the study had not bought a medicine prescribed by a doctor for financial reasons in the last six months. Based on the study, about a third of medicine users have remained unclear regarding medicine reimbursements, and not everyone feels that they have received sufficient counselling and information about medicine prices and medicine reimbursements when buying prescription medicines from a pharmacy. Counselling from a pharmacy was found to be related to understanding of medicine reimbursement criteria. Advise on the pricing, medicine reimbursement and generic substitution should continue to be actively provided to medicine users, so that the counselling meets the requirements of the law and the knowledge of the reimbursement system of medicine users can be improved. Based on the results of this study, counselling should be targeted in particular at younger, low-income and from mental health problems suffering medicine users, as well as those who are less familiar with reimbursement issues, for example due to low morbidity or medicine use.

Good availability of medicines means that authorised medicines are placed on the market and not in a short supply. Drug shortages have increasingly become a common problem that has compromised the continuous availability of medicines. Drug shortages are caused by many complex factors, such as capacity constraints, manufacturing difficulties, business decisions, availability of raw materials, and sudden increase in demand. Drug shortages can cause adverse effects, medication errors, allergies, and delays in necessary treatments. There have been studies that have explained the reasons behind medicines shortages. However, more information is needed especially from the perspective of markets in Finland. The aim of this study was to reinforce and deepen the knowledge concerning the availability of medicines in Finland. The aim was to identify the group of medicines that are more exposed in short supply than others and define the root causes of medicine shortages. In addition, the aim was to form an overview of the availability of medicines in Finland. The study was based on a Finnish medicine agency's registry. Data were collected retrospectively from materials that contained shortage notifications from marketing authorisation holders and mandatory reserve supplies permissions for exemption to maintain lower stock levels. The study was dated between the years 2017 and 2020. More detailed data from the medicine shortage was only available from the year 2020 because of changes in procedures. The study also contained data from the register for all marketed and non-marketed medicinal products with marketing authorisation. The data classified with ATC-codes, because it is used internationally and thus makes the study to comparative to other studies. Data were analysed with cross-tabulation and frequency distributions. The study addressed that drug shortages were reported of medicines that are commonly used in Finland, such as nervous and cardiovascular system drugs. These medicines covered almost half of the annual shortage notifications. The number of drug shortage notifications has increased annually by approximately 40 percent. Correspondingly mandatory reserve supplies permission for an exemption to maintain lower stock levels were reported most on nervous system drugs and anti-infectives for systemic use. The number of annual permissions remained quite constant. The amount of the permissions increased 14 percent between the years 2017 and 2018 and a further 6 percent to the year 2019. However, the amount of permissions increased 26 percent in the year 2020. There is clearly recognized the effect of the COVID-19 pandemic when considered the rate of shortage notifications and mandatory reserve supplies permissions. The main reasons for the shortages were capacity constraints (32%) and increased demand (21%). Most of the drugs in short supply were drugs with national (33%) or decentralised (30%) marketing authorisation procedures. Broadly were able to state that the availability of medicines was at an acceptable level. 62 percent of all medicinal products with marketing authorisation were placed on the market. In addition, only 29 percent of older drugs with marketing authorisation accept during the years 1996 to 2003 were withdrawn from the market. In future, more large-scale studies are needed based on this study to improve the system that maintains the continuous and high-quality medicine distribution. Most important is to create a better tracking system and co-operation between national and international officials.

Left ventricular hypertrophy (LVH) takes place when cardiomyocytes respond to excessive stress by growing in size. Cardiomyocytes have a very marginal capability to proliferate, which is why hypertrophic growth is almost their only option to meet the requirements of increased workload. In the long run, however, LVH leads to further problems, such as cardiac failure and an increased risk of myocardial infarction. Hypertension is the most prevalent cause of LVH, and its current treatment relies on antihypertensive drugs. They decrease the workload of the heart and therefore alleviate symptoms but have very little effect on the built damage and remodeling. Understanding the details of cellular level signaling pathways and genetic expression in LVH is crucial for future drug development. Regulation of gene expression is a very complex process, which involves more than just DNA being translated into a protein. In this project, two types of factors participating in this regulation were in focus: long non-coding RNAs (lncRNA) and transcription factors GATA4 and FOG2. LncRNAs are RNA sequences of more than 200 nucleotides that do not code for any protein final products themselves but are involved in chromatin remodeling as well as transcriptional and post-transcriptional gene regulation. They are highly organ-selective, which makes them potential targets for drug development. Our group has previously found a selection of cardiomyocyte-selective lncRNAs, which share a similar expression pattern in neonatal mouse hearts. In this project, three of them were silenced in a primary cardiomyocyte culture while simultaneously hormonally inducing hypertrophy. The goal was to see whether these lncRNAs have an effect on the hypertrophic response and apoptosis in the cardiomyocytes. Transcription factors are proteins with partially similar activities to lncRNAs; they regulate, which genes are expressed under certain circumstances. GATA4 is an important transcription factor in the heart as it targets various developmental and functional genes in cardiomyocytes. FOG2 is a cofactor of GATA4; interaction between them regulates the activity of GATA4. Our group has recently developed a selection of compounds that affect protein-protein interaction between GATA4 and NKX2-5, another important transcription factor. The second part of the project was to set up and optimize a compound screening assay for GATA4-FOG2 interaction. The results showed no change in hypertrophic response when the lncRNAs were silenced. Other experimental designs could still reveal if they have effects that could not be seen with these protocols. The silencing had no effect on apoptosis. As for the GATA4-FOG2 interaction experiments, transfecting COS-1 with GATA4 and FOG2 plasmids in a ratio of 10:1 resulted in a signal suitable for compound screening. Initial compound screening results indicated the compounds may have an effect on GATA4-FOG2 interaction, but further studies are needed before drawing conclusions.

The package leaflet (“leaflet”) is a technical document included in medicine packages to provide information about the medicinal product to the user. With the EU now encouraging the adoption of eHealth, it can be assumed that written medicine information would be included in the digitalisation process. Medicine users’ views on electronic forms of medicine information should be assessed before any changes can be made, but so far there is very little data on this. The aim of this study was to find out what kind of leaflet medicine users would prefer and how they would feel about an electronic leaflet. The main aim was to find out if there is a difference in preferences between different types of medicine users and between medicine users of different ages in the provision of a package leaflet. The study also sought to find out if the current leaflet is being read by medicine users. This study was conducted by carrying out a survey to pharmacy customers over the age of 16 collecting prescription medication(s) for themselves (n = 110). The data was collected at one retail pharmacy in Helsinki, Finland during July 2020. The data was analysed quantitatively. This study found that medicine users generally feel positively about an electronic leaflet (liked by 63%) and many are open to idea of an electronic leaflet (75%). The majority (88%) could see positives in using an electronic leaflet, regardless of leaflet preferences. The study did not find a difference between new and repeat medicine users in the preference for a particular leaflet format, but age is correlated with the preference for a particular leaflet type, with younger medicine users wanting an electronic leaflet as often as older medicine users want a printed leaflet. Having the leaflet appear in My Kanta pages after the medication has been dispensed was found to be the most popular way to receive an electronic leaflet. This study also found that there is a difference between new and repeat medicine users when it comes to reading the leaflet after a medication has been dispensed. With the current printed leaflet 81% of repeat medicine users and 38% of new medicine users do not read it. The most common reason given for not reading the leaflet was that the participant had read it before and did not feel the need to read it again. According to this study, medicine users, especially younger medicine users, feel positively about the idea of an electronic leaflet, which is encouraging for the future of an electronic leaflet. The results are in line with prior research, but also suggest that more medicine users feel positively about the idea of an electronic leaflet than before. The leaflet reading behaviours of medicine users also highlight the need for a system, where a medicine user can be alerted to any changes in the leaflet, which is something only an electronic system could do.

Objectives To investigate distribution and causes of drug shortages in five selected countries with data from public shortage notification registers. Design Statistical retrospective analysis of national drug shortage registers Data Public shortage notification register data from the first nine months of 2020 in Finland, Sweden, Norway, Spain, and the United States, partly combined with national drug registers. Results Altogether 5132 shortage reports from Finland (n=1522), Sweden (n=890), Norway (n=800), Spain (n=814), and the United States (n=1106) published during the first nine months of 2020 were found in the study. More than half (54%) of the active ingredient level shortages (classified by ATC code) found occurred in only one country, and only 1% occurred in all five countries. On a country level, 19-41% of the shortages were found only in a given country. The distribution of shortages by ATC category and drug form was significantly different between countries, especially between the US and European countries. Injectables were found to have an especially high shortage risk in the US, much less so in European countries. On the other hand, some drug classes were in shortage almost exclusively in Europe but not in the US. Conclusions Although drug shortages are a growing global problem, drug shortages are rarely global, but typically occur only in some countries, while other countries have an uninterrupted supply of the same drug. Drug shortages should be seen not just as a problem of manufacturing disruptions, but as a question of equitable and effective distribution of drug supply on an international level. Price differences and other commercial issues could be factors behind variation of shortages found between countries.Considering the limited and probing nature of the study, further research of shortage register data is certainly warranted. International comparative register study is a meaningful and valid method for further understanding in this field.