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Primary non-adherence to inhaled medications measured with e-prescription data from Poland

Primary non-adherence to inhaled medications measured with e-prescription data from Poland Background: Treatment adherence greatly influences the clinical outcomes in various fields of medicine, including management of asthma and COPD. With the recent implementation of a nationwide e-Health solutions in Poland, new and unique opportunities for studying primary non-adherence in asthma and COPD emerged. The aim was to study primary non-adherence to inhaled medications available in Poland indicated in asthma and/or COPD and analyse the impact of patients’ demographics and inhalers’ characteristics (dry powder inhalers (DPIs) vs metered dose inhalers (MDIs) and presence of a dosage counter) on primary non-adherence. Methods: A retrospective analysis of all e-prescriptions issued in Poland in 2018 (n = 119,880) from the national e-prescription pilot framework. Results: Primary non-adherence for inhalable medications reached 15.3%. It significantly differed among age groups—the lowest (10.8%) was in 75 + years-old patients, highest (18%) in 65–74 years-old patients. No gender dif- ferences in primary non-adherence were found. The highest non-adherence was observed for ICS + LABA combina- tions (18.86%). A significant difference was found between MDI and DPI inhalers and between inhalers with/without a dosage counter. Conclusions: Out of e-prescriptions for inhaled medications issued in 2018 in Poland, 15.3% were not redeemed. The degree of primary non-adherence was influenced by age, but not gender. Significant differences between MDIs and DPIs and between inhalers with/without a dosage counter were observed. Keywords: Inhaled medications, Inhalators, Asthma adherence, COPD adherence, Primary non-adherence, e-prescription Introduction and chronic obstructive pulmonary disease (COPD). In Treatment adherence greatly influences the clinical out - course of these two conditions, the primary clinical role comes in various fields of medicine. In general, the worse is attributed to inhaled medications, which are important is the adherence, the worse are the health outcomes and in management of disease symptoms and natural course of the diseases. patients’ quality of life [1]. It is also a major determinant As asthma and COPD are frequent and most often of healthcare costs [2]. These effects also take place in chronic conditions, the key to their successful manage the management of obstructive lung diseases—asthma - ment comes with systematic drug use, particularly those inhaled. Specific drug selection depends on the diagno - *Correspondence: pkardas@csk.am.lodz.pl sis and indication, previous treatment response, disease First Department of Family Medicine, Medical University of Lodz, Lodz, severity, patient’s individual needs and preferences and Poland various other patient-related factors. The inhaled drugs Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Kardas et al. Clin Transl Allergy (2020) 10:39 Page 2 of 8 used in these two indications include: inhaled corticos- COPD—overall and for individual drugs. Additionally, teroids (ICS), short-acting beta-agonists (SABA), long- the impact of patients’ demographics on this phenom- acting beta-agonists (LABA) and long-acting muscarinic enon was analysed. The variation of primary non-adher - antagonists (LAMA) [3]. ence across different types of inhalers—(dry powder Asthma and COPD symptoms—their type and sever- inhalers (DPIs) vs metered dose inhalers (MDIs)) and ity—often vary among patients and also may change presence of a dosage counter within the inhaler was also over time. Although these diseases are life-threatening studied. conditions—especially during an exacerbation or severe We retrospectively analysed the data from all of breathlessness attack—in course of chronic treatment the e-prescriptions issued in Poland in 2018 (n = 119,880) patients still have some degree of freedom in self-man- from the national e-prescription pilot. The data came agement during stable, controlled periods of their disase. from 43 medical units (primary care, hospitals and spe- Despite that, efficient long-term asthma and COPD treat - cialist clinics from 9 out of 16 voivoidships of Poland). ment comes from the proper and regular use of inhaled The healthcare centres participating in this pilot pro - medications. In this case, adherence to treatment, and gramme were invited by CSIOZ (see below) or voluntary primary adherence in particular, greatly contributes to joined  voluntarily. The e-prescriptions were prescribed the therapeutic success. by 190 doctors of various specialisations. Defined in the ABC European consensus, medication The study  database was provided to the researchers adherence is as an active, cooperative and voluntary par- by the  Center of Information Systems for Healthcare ticipation of the patient in following recommendations (Centrum Systemów Informacyjnych Ochrony Zdrowia, from a healthcare provider. The process involves three CSIOZ)—a Polish  governmental institution working on crucial steps: the Polish healthcare system digitalization. A recent task of this institution was the implementa- tion of the nationwide system of e-prescriptions, which is • Initiation—defined as the moment the first dose is fully operational as of January 2020. taken by the patient; The  data used in the analysis was fully anonymized. • Implementation—defined by the extent of prescrip - uTh s, the  study was not subject to ethical approval, tion regimen fulfilment; according to the  Ethical Commission of Medical Uni- • Discontinuation—that is when the patient discontin- versity of Lodz. The records included basic patient char - ues taking the prescribed drugs [4]. acteristics (age and gender), the  date of prescription issuing, prescription details (drug  trade name,  dosage, In general, primary non-adherence is a situation when packages number), and details and date of drug dispen- a patient does not obtain the prescribed drug from the sation (only if it happened). In the literature, primary pharmacy during the prescription’s validity [5]. Hav- non-adherence is generally defined as not obtaining the ing assumed that a prescription for an individual drug medication within the defined number of days after pre - is a proof that the need for pharmacotherapy has been scribing [5]. However, the database used in this study did confirmed by a medical professional, primary non- not include exact clinical data (that is individual patient’s adherence is a major discordance from the treatment diagnosis) and the  long-term, individual prescription schedule. Many studies have covered aspects of primary histories were not possible to be studied. Therefore, for non-adherence, particularly in terms of chronic diseases’ this study purpose, we defined primary non-adherence management (e.g. hypertension, diabetes mellitus and as not obtaining an individual  e-prescription from the other) [6–9]. However, data on primary non-adherence pharmacy within 30  days, as it is the  general prescrip- in treatment of asthma and COPD is limited. Moreover, tion validity in Poland—including inhalable medications the issue of general primary non-adherence and of that prescriptions. for inhaled medications, has yet not been properly stud- In our analysis, we included all of the inhaled medica- ied in Poland because reliable data was lacking. Fortu- tions available in Poland as of December 2018, with all nately, the recent implementation of nationwide e-Health of their available doses and formulations (21 compound solutions in Poland created new and unique opportuni- combinations, over 100 available preparations - the ties for studying primary non-adherence in asthma and full list of analysed ATC codes is available in Table  1). COPD. Each of the available inhaled medications was catego- rized by the authors according to their characteristics as Methods either DPI, MDI, metered dose liquid inhaler (MDLI) or The aim was to study the primary non-adherence to nebulization. all of the inhaled medications available in Poland (as of December 2018) with indication for asthma and/or K ardas et al. Clin Transl Allergy (2020) 10:39 Page 3 of 8 Table 1 List of the compounds analyzed (with ATC codes) non-adherence for inhalable medicines reached 15.3%, as 1671 (84.7%) of e-prescriptions on those drugs were No. Drug class ATC code and drug name obtained by the patients. 1. ICS R03BA01 Beclometasone 995 (50.4%) e-prescriptions for inhalable drugs were 2. ICS R03BA02 Budesonide prescribed for males. Primary non-adherence among 3. ICS R03BA05 Fluticasone males reached 16.7% and it was not significantly differ - 4. ICS R03BA08 cyclesonide ent from that among females (13.9%, p = 0,086) (Table 2). 5. ICS + LABA R03AK06 fluticasone + salmeterol Moreover, none of the analysed inhaled medications was 6. ICS + LABA R03AK07 Budesonide + formoterol significantly more often redeemed by either of genders. 7. ICS + LABA R03AK08 Beclometasone + formoterol The patients who obtained their inhalable medi - 8. LABA R03AC13 formoterol cine e-prescriptions were slightly, but significantly 9. LABA R03AC12 salmeterol older on average than those who did not (65.8 ± 18.0 10. LABA R03AC18 indacaterol vs. 64.1 ± 17.1  years, respectively, p < 0.05). The further 11. LAMA R03AL06 clicopironium analysis of age-related primary non-adherence depend- 12. LAMA R03BB01 Ipratropium encies has shown significant differences between age 13. LAMA R03BB04 Tiotropium groups. The highest primary non-adherence (18.0%) was 14. LAMA R03BB07 Umeclidynium observed among patients aged 65-74, whilst the highest 15. LAMA + LABA R03AL03 Ipratropium + salbutamol primary adherence (89.2%) was among the 75 + years-old 16. LAMA + LABA R03AL04 Indacaterol + glycopyrronium patients (Fig. 1). 17. LAMA + LABA R03AL04 Olodoterol + tiotropium The extents of primary non-adherence to individual 18. LAMA +LABA R03AL03 Umeklidynium + wilanaterol inhaled medication drug classes is shown in Table 3. The 19. SABA R03AC02 Salbutamol most commonly prescribed groups were LABAs (422 20. SABA R03AC04 Fenoterol e-prescriptions, 16.82% non-adherent) and ICSs (419, 21. SABA + LAMA R03AK03 Fenoterol + ipratropium 13.37% non-adherent). For drugs of interest in this study, the mostly prescribed (346) was a LABA—formoterol. Primary non-adherence to this drug was 19.08%. Among SABAs, the most fre- First, the descriptive statistics of overall prevalence of quently prescribed was salbutamol—274 e-prescriptions, primary non-adherence were calculated. Following that, 14.6% primary non-adherence. The most frequently pre - the potential drivers of primary non-adherence (age and scribed LAMA was tiotropium—115 e-prescriptions, gender) were studied. Age was categorized into 5 groups: 16.52% primary non-adherence. The values for all of the 1–18, 19–39, 40–64  years, 65–74 and 75 + years. Cate- analysed inhalable drugs are presented in Table 4. gorical variables were expressed as proportions and com- Further analysis was focused on differences in primary pared between the groups using the χ  test. The statistics non-adherence in relation to inhaler type (DPI vs MDI) were calculated using the Statistica 10 software (TIBCO and characteristics (presence of dosage counter). A sta- Software Inc., USA). A  p  value of < 0.05 was considered tistically significant difference was found between DPIs significant. (995 e-prescriptions) and MDIs (759 e-prescriptions), for which the extents of primary non-adherence were 17.0% Results and 13.4% respectively. Within drug class groups, where Out of all (119,880) individual drugs prescribed on e-pre- comparison was possible (ICSs, ICS + L ABAs, L ABAs scriptions in Poland in 2018, 1973 (1.6%) were inhal- and LAMAs), that is for which both types of inhalers able medicines of interest for this study. The primary within a group were available, there were no statistically Table 2 Levels of primary non-adherence to inhaled medicines by gender, chi = 2935; p = 0,086 Patient Gender Summary Male Female N % N % N % Adherent 829 83.3 842 86.1 1671 84.7 Non-adherent 166 16.7 136 13.9 302 15.3 Summary 995 978 1973 Kardas et al. Clin Transl Allergy (2020) 10:39 Page 4 of 8 Fig. 1 Levels of inhaled medications primary adherence/non-adherence among age groups. Chi = 16,641; p = 0,0023 common part of these treatments are always inhaled Table 3 Primary non-adherence for  inhaled medication drug classes drugs. Those drugs are effective in reducing the respira - tory symptoms and in long-term disease management. Drug class Issued Redeemed Primary Primary non- Moreover, their effects are crucial in exacerbation pre - adherence adherence [%] [%] vention and reduction of life-threatening incidents and mortality rate. Nonetheless, in proper management of ICS 419 363 86.63 13.37 asthma and COPD patient adherence is a greatly contrib- ICS + LABA 350 284 81.14 18.86 uting factor [11, 12]. Medication adherence is considered LABA 422 351 83.18 16.82 a major factor contributing to asthma/COPD exacerba- LAMA 352 303 86.08 13.92 tions, mortality and disease course [13, 14]. LAMA + LABA 41 37 90.24 9.76 According to the literature, adherence is modified LAMA + SABA 1 1 100 0 by numerous factors: socio-economic (e.g. family and SABA 321 274 85.36 14.64 employment), healthcare system-related (e.g. drug infor- SABA + LAMA 67 58 86.57 13.43 mation and administration), condition-related (e.g. symptoms or lack of them), drug-related (e.g. drug regi- men, formulation and costs) and importantly–patient- significant differences in primary non-adherence. Among related (e.g. level of education, mental and psychological MDIs and DPIs, the inhalers without a dosage coun- condition, health beliefs and concerns, cognitive func- ter had significantly lower primary non-adherence than tions) [15–17]. In particular, studies show that adher- those with it - 13.4% vs. 17.0% respectively ( chi = 4145; ence in COPD is device-related, with the device design p = 0,0415). Within MDI and DPI groups such differ - resulting in under- or overuse, depending on its technical ences were not significant. characteristics (dosage counter, the possibility to load an inhalation dose without real inhalation) [18]. Moreover, studies show that in asthma adherence is dependent on Discussion patient treatment beliefs and perception [19]. Inhalable medicines are the established basis of asthma In order to assess the patients’ adherence, a number and COPD management according to GINA and of methods may be implemented. These include direct GOLD recommendations [3, 10]. Depending on the dis- (e.g. drug or biomarker blood concentration) or indirect eases’ course and severity, a proper treatment scheme methods (e.g. pill counts, database research, self-reports) of asthma/COPD should be implemented, yet still a K ardas et al. Clin Transl Allergy (2020) 10:39 Page 5 of 8 Table 4 Primary non-adherence to individual inhaled medications Drug Class ATC code and drug name Issued Redeemed Primary adherence Primary non- [%] adherence [%] ICS R03BA01 Beclometasone – – – – ICS R03BA02 Budesonide 268 230 85,82 14.18 ICS R03BA05 Fluticasone 48 41 85,42 14.58 ICS R03BA08 Cyclesonide 103 92 89,32 10.68 ICS + LABA R03AK06 Fluticasone + salmeterol 178 157 88,20 11.8 ICS + LABA R03AK07 Budesonide + formoterol 88 58 65,91 34.09 ICS + LABA R03AK08 Beclometasone + formoterol 84 69 82,14 17.86 LABA R03AC13 Formoterol 346 280 80,92 19.08 LABA R03AC12 Salmeterol 72 67 93,06 6.94 LABA R03AC18 Indacaterol 4 4 100,0 0 LAMA R03AL06 Glicopironium 19 16 84,21 15.79 LAMA R03BB01 Ipratropium 209 183 87,56 12.44 LAMA R03BB04 Tiotropium 115 96 83,48 16.52 LAMA R03BB07 Umeclidynium 9 8 88,89 11.11 LAMA + LABA R03AL03 Ipratropium + salbutamol 1 1 100,0 0 LAMA + LABA R03AL04 Indacaterol + glycopyrronium 27 25 92,59 7.41 LAMA + LABA R03AL04 Olodoterol + tiotropium 6 5 83,33 16.67 LAMA + LABA R03AL03 Umeklidynium + wilanaterol 8 7 87,50 12.5 SABA R03AC02 Salbutamol 274 234 85,40 14.6 SABA R03AC04 Fenoterol 47 40 85,11 14.89 SABA + LAMA R03AK03 Fenoterol + Ipratropium 67 58 86,57 13.43 [20]. The use of e-prescription databases is subject to literature. With an approach similar to ours, Fischer et al. minimized bias in assessment of primary non-adherence, analysed primary non-adherence using data from 195,930 since the prescription drugs may legally only be obtained e-prescriptions from the United States. For “asthma med- when a patient possesses a prescription and fills it at a ications”, the primary non-adherence level reached 19.9% pharmacy. Self-report measures are considered not suf- in adults aged 19 + and 11.4% in children. For newly pre- ficiently precise and unreliable compared to other meth - scribed drugs in this field it reached 25.1% in adults and ods. Pill or dosage counts possibly overestimate the exact 11.3% in children. Similarly to our approach, the authors doses taken, as patients may influence the amount of of that study analysed only the population of patients that those left in the package [21–23]. However, to properly used the e-prescriptions. In another study, also by Fis- assess the primary adherence in community setting, no cher et al., primary non-adherence to “Antiasthmatic and other method than database search provides the most bronchodilator agents” medications reached 17.9% [27, accurate data [24]. 28]. Depending on the definition, setting and method - A meta-analysis of 31 articles on primary non-adher- ology used, primary non-adherence to various drugs ence published in 2019 by Cheen et  al. summarized the reaches different levels. In accordance to definition used results of 6 studies in asthma/COPD area published in in this study, it reaches a wide range of extents in dif- years 2009–2014. The levels of primary non-adherence to ferent settings. In  an analysis performed in the USA by the asthma/COPD medications ranged between 9 to 25%, Rutherford et al. four important drug groups—antihyper- with an average of 14.0%. In comparison, for other thera- tensives, lipid-lowering agents, hypoglycemics, and anti- peutic areas covered in this meta-analysis, the primary depressants—were found to reach a mean level of 14.6% non-adherence reached 25.0% for osteoporosis, 16.0% primary non-adherence [25], whereas e.g. for dermato- for hypertension, 10.0% for diabetes, 25.0% for hyperlipi- logical drugs primary non-adherence reached 24.7% [26]. demia and 12.0% for depression (17.0% across all groups). Few studies have covered the issue of inhaled medi- The authors also indicated several factors significantly cations primary non-adherence. Yet some examples associated with primary non-adherence, in particular in addressing this phenomenon may be found in the asthma/COPD, of which positively correlated older age Kardas et al. Clin Transl Allergy (2020) 10:39 Page 6 of 8 and male gender and higher co-payment. Interestingly, e-prescription system for the eldest cannot be proven. the authors did not confirm a dependence resulting from The study database originated from a nationwide pilot differences in dosage forms [29]. e-prescription programme, thus it can be considered The impact of inhaler type (MDI vs DPI) on primary complete. non-adherence has been subject  of only few analyses up A further study limitation was that it was only possible to date. In 2014 van Boven et al. used a Dutch pharmacy to analyse the primary non-adherence, that is studying dispensing data from 1994 to 2012 in order to analyse the act of obtaining/not obtaining a particular e-pre- LABA persistence in COPD patients. The authors of that scription. The number of doses a patient took or skipped study found no significant differences between MDIs and was also not measured. This issue could not be analysed DPIs [30]. We believe the differences observed in our with the data used in this study and, in fact, this was not study might be a result of generally lower out-of-pocket an objective of this study. A longitudinal analysis of a par- costs of MDIs, as compared to DPIs. Of a note is that ticular patient was also not possible to be performed with in Polish healthcare system, patients pay various drugs the analysed dataset. co-payments (with varying drug reimbursement levels: Finally, we could not analyse the exact reasons behind 100%, 70%, 50%, 0% or a standard co-payment of 3.20 the primary non-adherence, which could have been PLN per package), that are dependent on the drug, indi- diverse: disbelief in diagnosis or physician, drug char- cation, patient’s age and other. acteristics and other [15]. We also could not analyse the A number of interesting results on primary non-adher- impact of patients’ out-of–pocket costs (in Poland these ence to inhaled medications have been presented in this are dependent on indication, age and having a national paper. Using the data of highest possible quality available health insurance) on primary non-adherence, since the to date, that originated from a nationwide e-prescrip- database did not include the data on that subject. tion database, a specific level of primary non-adherence The use of e-prescription is rising recently, both in to inhaled medications in Poland was proven. The non- Europe and worldwide. Studies on e-prescription sys- adherence to these drugs was lower than obtained in our tems in Europe show their multi area benefits: health, previous study on drivers of general non-adherence in economic, social, patient-oriented and other. Major Poland, where for drugs in 6 major areas (antidiabetic, health benefits include reduced medication errors, bet - antithrombotic, cardiovascular, cholesterol medications, ter medicine accessibility and, what we recognize as cru- antibiotics and psychiatric drugs) the primary non- cial in therapy—increased monitoring of adherence. The adherence was 20.8% [31]. Also, it was lower than of that economic benefits include efficiency gains for healthcare for antihistamine drugs, for which the level of primary professionals, better transparency, reduced frauds and non-adherence was 21% [32]. printing costs. The social profits concentrate around Importantly, this is the very first study that covered pri - patient satisfaction, financial relief and assistance for the mary non-adherence to inhaled medications in Poland elderly [33]. Patients using e-prescriptions gain a possi- and also one of the very few such studies worldwide. A bility to trace their medication history better via a patient certain limitation of this study came from the database on-line portal. Finally, e-prescriptions help patients to structure, as it was not possible to study the exact clini- adapt to other tele-health solutions, such as teleconsul- cal reasons of each e-prescription. The data was anony - tations, and are of great help in case of limited physical mous and no additional clinical data (in particular, the access to healthcare facilities (e.g. recent coronavirus patient’s diagnosis) were available. However, this study outbreak). can still be considered an objective measure of adher- Regardless of why patients are non-adherent to inhaled ence in obstructive diseases, since the analysed drugs’ medications or other drugs, some corrective solutions approved indications (as reflected in their Summaries of are described. In a randomized trial of allergic rhini- Product Characteristics) include only asthma and COPD tis treatment with intranasal corticosteroid treatment, a management. Also noteworthy is the fact that during daily short message service reminder improved patient data collection, the new e-healthcare system  in Poland adherence [34]. Another SMS service for asthma patients was a pilot solution, and thus the primary non-adher- that reminded about their daily inhaled medications was ence results may have been influenced. Despite that, we effective and increased adherence by 17.8% [35]. Such believe  the data used in this study is still of the highest an approach–an SMS reminder to obtain an e-prescrip- possible quality and minimally biased. It was not self- tion  would possibly better primary adherence. As the reported nor dependent on any physicians’ opinion on e-prescription solution in  Poland in fact includes SMS patients’ non-adherence. As the lowest degree of primary service, this approach could be simply implemented with non-adherence concerned patients aged 75 + , the com- a reminder of a particular e-prescription expiration date mon perception of a possible technological barrier of an approaching. K ardas et al. Clin Transl Allergy (2020) 10:39 Page 7 of 8 Availability of data and materials A study of improving adherence to ICSs in asthma by The data set is available from the corresponding author upon reasonable Vollmer et al. has shown a small, yet significant improve - request. ment with an interactive voice recognition phone calls Ethics approval and consent to participate system that reminded patients of their medication refills The data used in the analysis was fully anonymized. Thus, the study was not and continuous ICS treatment. Such system, if fact simi- subject to ethical approval, according to the Ethical Commission of Medical lar to SMS service, could also improve primary adherence University of Lodz. in pair with e-prescription system [36]. Other approaches Consent for publication described in the literature include mobile apps that stress Not applicable. the significance of proper clinical allergy diagnosis and Competing interests further encourage patients’ adherence [37–39]. The authors declare that they have no competing interests. In order to better picture the observed phenomenon, in our future research we intend to further broaden the Author details Department of Internal Medicine, Asthma and Allergy, Medical University analysis spectrum. This will be achieved by inclusion of of Lodz, Lodz, Poland. First Department of Family Medicine, Medical Univer- higher number e-prescription databases, obtained in sity of Lodz, Lodz, Poland. 2019 and further. 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Primary nonadherence [cited 2020 Jul 3]; 7(1):39. http://ctajo urnal .biome dcent ral.com/artic to medication and its drivers in Poland: findings from the electronic les/10.1186/s1360 1-017-0175-6. prescription pilot analysis. Polish Arch Intern Med. 2020;130(1):8–16. 18. Rogliani P, Ora J, Puxeddu E, Matera MG, Cazzola M. Adherence to COPD 32. Kardas G, Panek M, Kuna P, Cieszyński J, Kardas P. Primary Non-Adherence treatment: Myth and reality. Vol. 129, Respiratory Medicine. W.B. Saunders to Antihistamines—Conclusions From E-Prescription Pilot Data in Poland. Ltd; 2017. p. 117–23. Front Pharmacol [Internet]. 2020 [cited 2020 Jun 18];11:783. https ://www. 19. Lycett H, Wildman E, Raebel EM, Sherlock J-P, Kenny T, Hai A, et al. front iersi n.org/artic le/10.3389/fphar .2020.00783 /full. Treatment perceptions in patients with asthma: Synthesis of factors 33. Deetjen U. European E-Prescriptions: Benefits and Success Factors [Inter - influencing adherence. 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Pilot study of mobile phone technology in allergic rhinitis in Euro- ness on adherence and preference for oncedaily vs. twice-daily medica- pean countries: the MASK-rhinitis study. Allergy [Internet]. 2017 [cited tion. Prim Care Respir Med. 2017. 27(1):1–11. 2019 Apr 14];72(6):857–65. http://www.ncbi.nlm.nih.gov/pubme d/28072 24. Steiner JF, Prochazka AV. The assessment of refill compliance using 463. pharmacy records: Methods, validity, and applications. J Clin Epidemiol. 38. Cingi C, Yorgancioglu A, Cingi CC, Oguzulgen K, Muluk NB, Ulusoy S, et al. 1997;50(1):105–16. The “physician on call patient engagement trial” (POPET ): measuring the 25. Lemstra M, Nwankwo C, Bird Y, Moraros J. Primary nonadherence to impact of a mobile patient engagement application on health outcomes chronic disease medications: A meta-analysis. Vol. 12, Patient Preference and quality of life in allergic rhinitis and asthma patients. Int Forum and Adherence. Dove Medical Press Ltd.; 2018. p. 721–31. Allergy Rhinol [Internet]. 2015 [cited 2019 Apr 14]; 5(6):487–97. http:// 26. Rutherford A, Glass DA, Suarez EA, Adamson AS. Prescription-level factors www.ncbi.nlm.nih.gov/pubme d/25856 270. associated with primary nonadherence to dermatologic medications. J 39. Van Boven JFM, Trappenburg JCA, Van Der Molen T, Chavannes NH. Dermatolog Treat. 2018;29(3):300–4. Towards tailored and targeted adherence assessment to optimise asthma 27. Fischer MA, Choudhry NK, Brill G, Avorn J, Schneeweiss S, Hutchins D, management. Vol. 25, npj Primary Care Respiratory Medicine. Nature et al. Trouble Getting Started: Predictors of Primary Medication Nonad- Publishing Group; 2015. p. 1–6. herence. Am J Med [Internet]. 2011 [cited 2019 Apr 14]; 124(11):1081. e9-1081.e22. https ://linki nghub .elsev ier.com/retri eve/pii/S0002 93431 Publisher’s Note 10049 06. Springer Nature remains neutral with regard to jurisdictional claims in pub- 28. Fischer MA, Stedman MR, Lii J, Vogeli C, Shrank WH, Brookhart MA, et al. lished maps and institutional affiliations. Primary Medication Non-Adherence: Analysis of 195,930 Electronic Ready to submit your research ? Choose BMC and benefit from: fast, convenient online submission thorough peer review by experienced researchers in your field rapid publication on acceptance support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Translational Allergy Springer Journals

Primary non-adherence to inhaled medications measured with e-prescription data from Poland

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Abstract

Background: Treatment adherence greatly influences the clinical outcomes in various fields of medicine, including management of asthma and COPD. With the recent implementation of a nationwide e-Health solutions in Poland, new and unique opportunities for studying primary non-adherence in asthma and COPD emerged. The aim was to study primary non-adherence to inhaled medications available in Poland indicated in asthma and/or COPD and analyse the impact of patients’ demographics and inhalers’ characteristics (dry powder inhalers (DPIs) vs metered dose inhalers (MDIs) and presence of a dosage counter) on primary non-adherence. Methods: A retrospective analysis of all e-prescriptions issued in Poland in 2018 (n = 119,880) from the national e-prescription pilot framework. Results: Primary non-adherence for inhalable medications reached 15.3%. It significantly differed among age groups—the lowest (10.8%) was in 75 + years-old patients, highest (18%) in 65–74 years-old patients. No gender dif- ferences in primary non-adherence were found. The highest non-adherence was observed for ICS + LABA combina- tions (18.86%). A significant difference was found between MDI and DPI inhalers and between inhalers with/without a dosage counter. Conclusions: Out of e-prescriptions for inhaled medications issued in 2018 in Poland, 15.3% were not redeemed. The degree of primary non-adherence was influenced by age, but not gender. Significant differences between MDIs and DPIs and between inhalers with/without a dosage counter were observed. Keywords: Inhaled medications, Inhalators, Asthma adherence, COPD adherence, Primary non-adherence, e-prescription Introduction and chronic obstructive pulmonary disease (COPD). In Treatment adherence greatly influences the clinical out - course of these two conditions, the primary clinical role comes in various fields of medicine. In general, the worse is attributed to inhaled medications, which are important is the adherence, the worse are the health outcomes and in management of disease symptoms and natural course of the diseases. patients’ quality of life [1]. It is also a major determinant As asthma and COPD are frequent and most often of healthcare costs [2]. These effects also take place in chronic conditions, the key to their successful manage the management of obstructive lung diseases—asthma - ment comes with systematic drug use, particularly those inhaled. Specific drug selection depends on the diagno - *Correspondence: pkardas@csk.am.lodz.pl sis and indication, previous treatment response, disease First Department of Family Medicine, Medical University of Lodz, Lodz, severity, patient’s individual needs and preferences and Poland various other patient-related factors. The inhaled drugs Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Kardas et al. Clin Transl Allergy (2020) 10:39 Page 2 of 8 used in these two indications include: inhaled corticos- COPD—overall and for individual drugs. Additionally, teroids (ICS), short-acting beta-agonists (SABA), long- the impact of patients’ demographics on this phenom- acting beta-agonists (LABA) and long-acting muscarinic enon was analysed. The variation of primary non-adher - antagonists (LAMA) [3]. ence across different types of inhalers—(dry powder Asthma and COPD symptoms—their type and sever- inhalers (DPIs) vs metered dose inhalers (MDIs)) and ity—often vary among patients and also may change presence of a dosage counter within the inhaler was also over time. Although these diseases are life-threatening studied. conditions—especially during an exacerbation or severe We retrospectively analysed the data from all of breathlessness attack—in course of chronic treatment the e-prescriptions issued in Poland in 2018 (n = 119,880) patients still have some degree of freedom in self-man- from the national e-prescription pilot. The data came agement during stable, controlled periods of their disase. from 43 medical units (primary care, hospitals and spe- Despite that, efficient long-term asthma and COPD treat - cialist clinics from 9 out of 16 voivoidships of Poland). ment comes from the proper and regular use of inhaled The healthcare centres participating in this pilot pro - medications. In this case, adherence to treatment, and gramme were invited by CSIOZ (see below) or voluntary primary adherence in particular, greatly contributes to joined  voluntarily. The e-prescriptions were prescribed the therapeutic success. by 190 doctors of various specialisations. Defined in the ABC European consensus, medication The study  database was provided to the researchers adherence is as an active, cooperative and voluntary par- by the  Center of Information Systems for Healthcare ticipation of the patient in following recommendations (Centrum Systemów Informacyjnych Ochrony Zdrowia, from a healthcare provider. The process involves three CSIOZ)—a Polish  governmental institution working on crucial steps: the Polish healthcare system digitalization. A recent task of this institution was the implementa- tion of the nationwide system of e-prescriptions, which is • Initiation—defined as the moment the first dose is fully operational as of January 2020. taken by the patient; The  data used in the analysis was fully anonymized. • Implementation—defined by the extent of prescrip - uTh s, the  study was not subject to ethical approval, tion regimen fulfilment; according to the  Ethical Commission of Medical Uni- • Discontinuation—that is when the patient discontin- versity of Lodz. The records included basic patient char - ues taking the prescribed drugs [4]. acteristics (age and gender), the  date of prescription issuing, prescription details (drug  trade name,  dosage, In general, primary non-adherence is a situation when packages number), and details and date of drug dispen- a patient does not obtain the prescribed drug from the sation (only if it happened). In the literature, primary pharmacy during the prescription’s validity [5]. Hav- non-adherence is generally defined as not obtaining the ing assumed that a prescription for an individual drug medication within the defined number of days after pre - is a proof that the need for pharmacotherapy has been scribing [5]. However, the database used in this study did confirmed by a medical professional, primary non- not include exact clinical data (that is individual patient’s adherence is a major discordance from the treatment diagnosis) and the  long-term, individual prescription schedule. Many studies have covered aspects of primary histories were not possible to be studied. Therefore, for non-adherence, particularly in terms of chronic diseases’ this study purpose, we defined primary non-adherence management (e.g. hypertension, diabetes mellitus and as not obtaining an individual  e-prescription from the other) [6–9]. However, data on primary non-adherence pharmacy within 30  days, as it is the  general prescrip- in treatment of asthma and COPD is limited. Moreover, tion validity in Poland—including inhalable medications the issue of general primary non-adherence and of that prescriptions. for inhaled medications, has yet not been properly stud- In our analysis, we included all of the inhaled medica- ied in Poland because reliable data was lacking. Fortu- tions available in Poland as of December 2018, with all nately, the recent implementation of nationwide e-Health of their available doses and formulations (21 compound solutions in Poland created new and unique opportuni- combinations, over 100 available preparations - the ties for studying primary non-adherence in asthma and full list of analysed ATC codes is available in Table  1). COPD. Each of the available inhaled medications was catego- rized by the authors according to their characteristics as Methods either DPI, MDI, metered dose liquid inhaler (MDLI) or The aim was to study the primary non-adherence to nebulization. all of the inhaled medications available in Poland (as of December 2018) with indication for asthma and/or K ardas et al. Clin Transl Allergy (2020) 10:39 Page 3 of 8 Table 1 List of the compounds analyzed (with ATC codes) non-adherence for inhalable medicines reached 15.3%, as 1671 (84.7%) of e-prescriptions on those drugs were No. Drug class ATC code and drug name obtained by the patients. 1. ICS R03BA01 Beclometasone 995 (50.4%) e-prescriptions for inhalable drugs were 2. ICS R03BA02 Budesonide prescribed for males. Primary non-adherence among 3. ICS R03BA05 Fluticasone males reached 16.7% and it was not significantly differ - 4. ICS R03BA08 cyclesonide ent from that among females (13.9%, p = 0,086) (Table 2). 5. ICS + LABA R03AK06 fluticasone + salmeterol Moreover, none of the analysed inhaled medications was 6. ICS + LABA R03AK07 Budesonide + formoterol significantly more often redeemed by either of genders. 7. ICS + LABA R03AK08 Beclometasone + formoterol The patients who obtained their inhalable medi - 8. LABA R03AC13 formoterol cine e-prescriptions were slightly, but significantly 9. LABA R03AC12 salmeterol older on average than those who did not (65.8 ± 18.0 10. LABA R03AC18 indacaterol vs. 64.1 ± 17.1  years, respectively, p < 0.05). The further 11. LAMA R03AL06 clicopironium analysis of age-related primary non-adherence depend- 12. LAMA R03BB01 Ipratropium encies has shown significant differences between age 13. LAMA R03BB04 Tiotropium groups. The highest primary non-adherence (18.0%) was 14. LAMA R03BB07 Umeclidynium observed among patients aged 65-74, whilst the highest 15. LAMA + LABA R03AL03 Ipratropium + salbutamol primary adherence (89.2%) was among the 75 + years-old 16. LAMA + LABA R03AL04 Indacaterol + glycopyrronium patients (Fig. 1). 17. LAMA + LABA R03AL04 Olodoterol + tiotropium The extents of primary non-adherence to individual 18. LAMA +LABA R03AL03 Umeklidynium + wilanaterol inhaled medication drug classes is shown in Table 3. The 19. SABA R03AC02 Salbutamol most commonly prescribed groups were LABAs (422 20. SABA R03AC04 Fenoterol e-prescriptions, 16.82% non-adherent) and ICSs (419, 21. SABA + LAMA R03AK03 Fenoterol + ipratropium 13.37% non-adherent). For drugs of interest in this study, the mostly prescribed (346) was a LABA—formoterol. Primary non-adherence to this drug was 19.08%. Among SABAs, the most fre- First, the descriptive statistics of overall prevalence of quently prescribed was salbutamol—274 e-prescriptions, primary non-adherence were calculated. Following that, 14.6% primary non-adherence. The most frequently pre - the potential drivers of primary non-adherence (age and scribed LAMA was tiotropium—115 e-prescriptions, gender) were studied. Age was categorized into 5 groups: 16.52% primary non-adherence. The values for all of the 1–18, 19–39, 40–64  years, 65–74 and 75 + years. Cate- analysed inhalable drugs are presented in Table 4. gorical variables were expressed as proportions and com- Further analysis was focused on differences in primary pared between the groups using the χ  test. The statistics non-adherence in relation to inhaler type (DPI vs MDI) were calculated using the Statistica 10 software (TIBCO and characteristics (presence of dosage counter). A sta- Software Inc., USA). A  p  value of < 0.05 was considered tistically significant difference was found between DPIs significant. (995 e-prescriptions) and MDIs (759 e-prescriptions), for which the extents of primary non-adherence were 17.0% Results and 13.4% respectively. Within drug class groups, where Out of all (119,880) individual drugs prescribed on e-pre- comparison was possible (ICSs, ICS + L ABAs, L ABAs scriptions in Poland in 2018, 1973 (1.6%) were inhal- and LAMAs), that is for which both types of inhalers able medicines of interest for this study. The primary within a group were available, there were no statistically Table 2 Levels of primary non-adherence to inhaled medicines by gender, chi = 2935; p = 0,086 Patient Gender Summary Male Female N % N % N % Adherent 829 83.3 842 86.1 1671 84.7 Non-adherent 166 16.7 136 13.9 302 15.3 Summary 995 978 1973 Kardas et al. Clin Transl Allergy (2020) 10:39 Page 4 of 8 Fig. 1 Levels of inhaled medications primary adherence/non-adherence among age groups. Chi = 16,641; p = 0,0023 common part of these treatments are always inhaled Table 3 Primary non-adherence for  inhaled medication drug classes drugs. Those drugs are effective in reducing the respira - tory symptoms and in long-term disease management. Drug class Issued Redeemed Primary Primary non- Moreover, their effects are crucial in exacerbation pre - adherence adherence [%] [%] vention and reduction of life-threatening incidents and mortality rate. Nonetheless, in proper management of ICS 419 363 86.63 13.37 asthma and COPD patient adherence is a greatly contrib- ICS + LABA 350 284 81.14 18.86 uting factor [11, 12]. Medication adherence is considered LABA 422 351 83.18 16.82 a major factor contributing to asthma/COPD exacerba- LAMA 352 303 86.08 13.92 tions, mortality and disease course [13, 14]. LAMA + LABA 41 37 90.24 9.76 According to the literature, adherence is modified LAMA + SABA 1 1 100 0 by numerous factors: socio-economic (e.g. family and SABA 321 274 85.36 14.64 employment), healthcare system-related (e.g. drug infor- SABA + LAMA 67 58 86.57 13.43 mation and administration), condition-related (e.g. symptoms or lack of them), drug-related (e.g. drug regi- men, formulation and costs) and importantly–patient- significant differences in primary non-adherence. Among related (e.g. level of education, mental and psychological MDIs and DPIs, the inhalers without a dosage coun- condition, health beliefs and concerns, cognitive func- ter had significantly lower primary non-adherence than tions) [15–17]. In particular, studies show that adher- those with it - 13.4% vs. 17.0% respectively ( chi = 4145; ence in COPD is device-related, with the device design p = 0,0415). Within MDI and DPI groups such differ - resulting in under- or overuse, depending on its technical ences were not significant. characteristics (dosage counter, the possibility to load an inhalation dose without real inhalation) [18]. Moreover, studies show that in asthma adherence is dependent on Discussion patient treatment beliefs and perception [19]. Inhalable medicines are the established basis of asthma In order to assess the patients’ adherence, a number and COPD management according to GINA and of methods may be implemented. These include direct GOLD recommendations [3, 10]. Depending on the dis- (e.g. drug or biomarker blood concentration) or indirect eases’ course and severity, a proper treatment scheme methods (e.g. pill counts, database research, self-reports) of asthma/COPD should be implemented, yet still a K ardas et al. Clin Transl Allergy (2020) 10:39 Page 5 of 8 Table 4 Primary non-adherence to individual inhaled medications Drug Class ATC code and drug name Issued Redeemed Primary adherence Primary non- [%] adherence [%] ICS R03BA01 Beclometasone – – – – ICS R03BA02 Budesonide 268 230 85,82 14.18 ICS R03BA05 Fluticasone 48 41 85,42 14.58 ICS R03BA08 Cyclesonide 103 92 89,32 10.68 ICS + LABA R03AK06 Fluticasone + salmeterol 178 157 88,20 11.8 ICS + LABA R03AK07 Budesonide + formoterol 88 58 65,91 34.09 ICS + LABA R03AK08 Beclometasone + formoterol 84 69 82,14 17.86 LABA R03AC13 Formoterol 346 280 80,92 19.08 LABA R03AC12 Salmeterol 72 67 93,06 6.94 LABA R03AC18 Indacaterol 4 4 100,0 0 LAMA R03AL06 Glicopironium 19 16 84,21 15.79 LAMA R03BB01 Ipratropium 209 183 87,56 12.44 LAMA R03BB04 Tiotropium 115 96 83,48 16.52 LAMA R03BB07 Umeclidynium 9 8 88,89 11.11 LAMA + LABA R03AL03 Ipratropium + salbutamol 1 1 100,0 0 LAMA + LABA R03AL04 Indacaterol + glycopyrronium 27 25 92,59 7.41 LAMA + LABA R03AL04 Olodoterol + tiotropium 6 5 83,33 16.67 LAMA + LABA R03AL03 Umeklidynium + wilanaterol 8 7 87,50 12.5 SABA R03AC02 Salbutamol 274 234 85,40 14.6 SABA R03AC04 Fenoterol 47 40 85,11 14.89 SABA + LAMA R03AK03 Fenoterol + Ipratropium 67 58 86,57 13.43 [20]. The use of e-prescription databases is subject to literature. With an approach similar to ours, Fischer et al. minimized bias in assessment of primary non-adherence, analysed primary non-adherence using data from 195,930 since the prescription drugs may legally only be obtained e-prescriptions from the United States. For “asthma med- when a patient possesses a prescription and fills it at a ications”, the primary non-adherence level reached 19.9% pharmacy. Self-report measures are considered not suf- in adults aged 19 + and 11.4% in children. For newly pre- ficiently precise and unreliable compared to other meth - scribed drugs in this field it reached 25.1% in adults and ods. Pill or dosage counts possibly overestimate the exact 11.3% in children. Similarly to our approach, the authors doses taken, as patients may influence the amount of of that study analysed only the population of patients that those left in the package [21–23]. However, to properly used the e-prescriptions. In another study, also by Fis- assess the primary adherence in community setting, no cher et al., primary non-adherence to “Antiasthmatic and other method than database search provides the most bronchodilator agents” medications reached 17.9% [27, accurate data [24]. 28]. Depending on the definition, setting and method - A meta-analysis of 31 articles on primary non-adher- ology used, primary non-adherence to various drugs ence published in 2019 by Cheen et  al. summarized the reaches different levels. In accordance to definition used results of 6 studies in asthma/COPD area published in in this study, it reaches a wide range of extents in dif- years 2009–2014. The levels of primary non-adherence to ferent settings. In  an analysis performed in the USA by the asthma/COPD medications ranged between 9 to 25%, Rutherford et al. four important drug groups—antihyper- with an average of 14.0%. In comparison, for other thera- tensives, lipid-lowering agents, hypoglycemics, and anti- peutic areas covered in this meta-analysis, the primary depressants—were found to reach a mean level of 14.6% non-adherence reached 25.0% for osteoporosis, 16.0% primary non-adherence [25], whereas e.g. for dermato- for hypertension, 10.0% for diabetes, 25.0% for hyperlipi- logical drugs primary non-adherence reached 24.7% [26]. demia and 12.0% for depression (17.0% across all groups). Few studies have covered the issue of inhaled medi- The authors also indicated several factors significantly cations primary non-adherence. Yet some examples associated with primary non-adherence, in particular in addressing this phenomenon may be found in the asthma/COPD, of which positively correlated older age Kardas et al. Clin Transl Allergy (2020) 10:39 Page 6 of 8 and male gender and higher co-payment. Interestingly, e-prescription system for the eldest cannot be proven. the authors did not confirm a dependence resulting from The study database originated from a nationwide pilot differences in dosage forms [29]. e-prescription programme, thus it can be considered The impact of inhaler type (MDI vs DPI) on primary complete. non-adherence has been subject  of only few analyses up A further study limitation was that it was only possible to date. In 2014 van Boven et al. used a Dutch pharmacy to analyse the primary non-adherence, that is studying dispensing data from 1994 to 2012 in order to analyse the act of obtaining/not obtaining a particular e-pre- LABA persistence in COPD patients. The authors of that scription. The number of doses a patient took or skipped study found no significant differences between MDIs and was also not measured. This issue could not be analysed DPIs [30]. We believe the differences observed in our with the data used in this study and, in fact, this was not study might be a result of generally lower out-of-pocket an objective of this study. A longitudinal analysis of a par- costs of MDIs, as compared to DPIs. Of a note is that ticular patient was also not possible to be performed with in Polish healthcare system, patients pay various drugs the analysed dataset. co-payments (with varying drug reimbursement levels: Finally, we could not analyse the exact reasons behind 100%, 70%, 50%, 0% or a standard co-payment of 3.20 the primary non-adherence, which could have been PLN per package), that are dependent on the drug, indi- diverse: disbelief in diagnosis or physician, drug char- cation, patient’s age and other. acteristics and other [15]. We also could not analyse the A number of interesting results on primary non-adher- impact of patients’ out-of–pocket costs (in Poland these ence to inhaled medications have been presented in this are dependent on indication, age and having a national paper. Using the data of highest possible quality available health insurance) on primary non-adherence, since the to date, that originated from a nationwide e-prescrip- database did not include the data on that subject. tion database, a specific level of primary non-adherence The use of e-prescription is rising recently, both in to inhaled medications in Poland was proven. The non- Europe and worldwide. Studies on e-prescription sys- adherence to these drugs was lower than obtained in our tems in Europe show their multi area benefits: health, previous study on drivers of general non-adherence in economic, social, patient-oriented and other. Major Poland, where for drugs in 6 major areas (antidiabetic, health benefits include reduced medication errors, bet - antithrombotic, cardiovascular, cholesterol medications, ter medicine accessibility and, what we recognize as cru- antibiotics and psychiatric drugs) the primary non- cial in therapy—increased monitoring of adherence. The adherence was 20.8% [31]. Also, it was lower than of that economic benefits include efficiency gains for healthcare for antihistamine drugs, for which the level of primary professionals, better transparency, reduced frauds and non-adherence was 21% [32]. printing costs. The social profits concentrate around Importantly, this is the very first study that covered pri - patient satisfaction, financial relief and assistance for the mary non-adherence to inhaled medications in Poland elderly [33]. Patients using e-prescriptions gain a possi- and also one of the very few such studies worldwide. A bility to trace their medication history better via a patient certain limitation of this study came from the database on-line portal. Finally, e-prescriptions help patients to structure, as it was not possible to study the exact clini- adapt to other tele-health solutions, such as teleconsul- cal reasons of each e-prescription. The data was anony - tations, and are of great help in case of limited physical mous and no additional clinical data (in particular, the access to healthcare facilities (e.g. recent coronavirus patient’s diagnosis) were available. However, this study outbreak). can still be considered an objective measure of adher- Regardless of why patients are non-adherent to inhaled ence in obstructive diseases, since the analysed drugs’ medications or other drugs, some corrective solutions approved indications (as reflected in their Summaries of are described. In a randomized trial of allergic rhini- Product Characteristics) include only asthma and COPD tis treatment with intranasal corticosteroid treatment, a management. Also noteworthy is the fact that during daily short message service reminder improved patient data collection, the new e-healthcare system  in Poland adherence [34]. Another SMS service for asthma patients was a pilot solution, and thus the primary non-adher- that reminded about their daily inhaled medications was ence results may have been influenced. Despite that, we effective and increased adherence by 17.8% [35]. Such believe  the data used in this study is still of the highest an approach–an SMS reminder to obtain an e-prescrip- possible quality and minimally biased. It was not self- tion  would possibly better primary adherence. As the reported nor dependent on any physicians’ opinion on e-prescription solution in  Poland in fact includes SMS patients’ non-adherence. As the lowest degree of primary service, this approach could be simply implemented with non-adherence concerned patients aged 75 + , the com- a reminder of a particular e-prescription expiration date mon perception of a possible technological barrier of an approaching. K ardas et al. Clin Transl Allergy (2020) 10:39 Page 7 of 8 Availability of data and materials A study of improving adherence to ICSs in asthma by The data set is available from the corresponding author upon reasonable Vollmer et al. has shown a small, yet significant improve - request. ment with an interactive voice recognition phone calls Ethics approval and consent to participate system that reminded patients of their medication refills The data used in the analysis was fully anonymized. Thus, the study was not and continuous ICS treatment. Such system, if fact simi- subject to ethical approval, according to the Ethical Commission of Medical lar to SMS service, could also improve primary adherence University of Lodz. in pair with e-prescription system [36]. Other approaches Consent for publication described in the literature include mobile apps that stress Not applicable. the significance of proper clinical allergy diagnosis and Competing interests further encourage patients’ adherence [37–39]. The authors declare that they have no competing interests. In order to better picture the observed phenomenon, in our future research we intend to further broaden the Author details Department of Internal Medicine, Asthma and Allergy, Medical University analysis spectrum. This will be achieved by inclusion of of Lodz, Lodz, Poland. First Department of Family Medicine, Medical Univer- higher number e-prescription databases, obtained in sity of Lodz, Lodz, Poland. 2019 and further. 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Fischer MA, Stedman MR, Lii J, Vogeli C, Shrank WH, Brookhart MA, et al. lished maps and institutional affiliations. Primary Medication Non-Adherence: Analysis of 195,930 Electronic Ready to submit your research ? Choose BMC and benefit from: fast, convenient online submission thorough peer review by experienced researchers in your field rapid publication on acceptance support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions

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