Drug Utilization 2024/2025 - Social Pharmacy, PDF

Drug utilization Department of Social and Clinical Pharmacy Faculty of Pharmacy in Hradec Králové, Charles University PharmDr. Zuzana Juhásová, Ph.D. Social Pharmacy 2024/2025 Drug utilization: lecture outline Drug utilization and factors influencing drug u...

Drug utilization Department of Social and Clinical Pharmacy Faculty of Pharmacy in Hradec Králové, Charles University PharmDr. Zuzana Juhásová, Ph.D. Social Pharmacy 2024/2025 Drug utilization: lecture outline Drug utilization and factors influencing drug utilization Drug utilization research The significance of drug utilization research prescribing Types of research and Types of data primary vs secondary data aggregate vs individual data Measurement dispensing ATC/DDD methodology Limitation of DDD (defined daily dose) PDD (prescribed daily dose), number of packages, prevalence, incidence,… Data sources Sales data, Pharmacy dispensing data, Electronic health records, Reimbursement data,Patient registries consumption Examples of studies  Drug Utilization = drug exposition in a given population, in a given time/period, and in a certain prescribing socioeconomic environment Drug utilization may be expressed in various measures: number of packages, number of prescriptions, weight units, dispensing number of prescribed daily doses (PDDs), number of defined daily doses (DDDs), proportion of patients taking the medication, financial costs consumption  Factors influencing drug utilization Drug shortages Factors influencing medication adherence are discussed within lecture Patient SmPC, guidelines attitudes and behaviours, including Clinical decision medication adherence support system Marketing Drug formularies Medication Regulatory actions adherence marketing authorization pricing and Medication review pharmaco- reimbursement epidemiology Health status of the population OTC medications  Factors influencing drug utilization Health Status of the Population (e.g. prevalence of chronic diseases, epidemiologic situation) Drug Policy: Drug policies, including processes of marketing authorization, pricing and reimbursement, play a significant role in drug availability and affordability. Reimbursement policies determine whether and how much the medication is covered by health insurance, which can greatly affect a patient’s ability to afford treatment (out-of-pocket costs) Regulatory agencies ensure drug safety through pharmacovigilance activities, new safety signals can alter perceptions of medications among healthcare professionals and the public. Hospital Formularies: Hospitals create drug formularies (lists of approved medications based on cost-effectiveness and clinical guidelines), that shape physicians' prescriptions. Physicians are key gatekeepers in prescription (Rx) drug utilization. Pharmacists influence drug utilization through medication review and medication dispensing, including generic substitution decisions (e.g., switching brand-name drugs to generics). Marketing can influence patient requests for specific drugs or physician prescribing practices. Guidelines, Clinical Decision Support Systems (CDSS), publications in scientific journals,...  Drug Utilization Research Drug Utilization Research is a discipline dedicated to the analysis and assessment of prescribing, dispensing and consumption of medications, with special emphasis on the resulting medical, social and economic consequences Aim of drug utilization research: → ensure rational use of medicines Right Right patient Right dosing and Right route of Acceptable Right drug duration of and indication dosage form administration costs treatment  History of drug utilization research 1975: publication of DDD (defined daily doses) 1979: WHO guideline for drug utilization research 1996: EuroDURG (European Drug Utilisation Research Group) Drug Utilization Research: Methods and Applications, First Edition. Elseviers M et al, eds. John Wiley & Sons Ltd; 2016. The pioneering drug utilization studies in Europe focused on assessing differences in drug utilization between countries or regions Analysis of trends International comparisons WHO International Working Group for Drug Statistics Methodology, WHO Collaborating Centre for Drug Statistics Methodology & WHO Collaborating Centre for Drug Utilization Research and Clinical Pharmacological Services. (2003). Introduction to drug utilization research. World Health Organization.  Drug utilization research Patient and provider characteristics, disease patterns Regulatory actions – e.g. changes in reimbursement Drug shortages prescribing Marketing Factors Drug Drug influencing drug Utilization formularies utilization = outcome dispensing Publication Guideline (Clinical) pharmacist consumption CDSS (clinical decision support system) Relationship between drug utilization research and pharmacoepidemiology Drug utilization research is an essential part of pharmacoepidemiology as it describes the extent and nature of drug exposure Pharmacoepidemiology is discussed within Pharmaceutical care I. Drug Utilization Research: Methods and Applications, First Edition. Elseviers M et al, eds. John Wiley & Sons Ltd; 2016.  The significance of drug utilization research ✓ indicator of appropriate/inappropriate ✓ to form health policy and assess the prescription impact of health policy initiatives ▪ to check whether prescription ✓ to monitor the impacts of risk corresponds with current standards: minimization measures in ▪ clinical guidelines pharmacovigilance ▪ SmPC ✓ pharmacoeconomic analyses ▪ antibiotic policy ✓ estimation of medication adherence ▪ drug formulary ✓ estimation of the prevalence or ▪ to find regions with overuse/underuse incidence of diseases that are treated ▪ indicator of medication abuse with corresponding medications ▪ assessment of off-label use ✓ exposure in pharmacoepidemiology  Type of research Quantitative research Qualitative research To measure prescribing, dispensing or To gain in‐depth understanding of the Objective consumption of medicines in prescribing, dispensing or consumption of populations medicines Tools e.g.: analyses of existing databases e.g.: in‐depth interviews Total data or statistically Small groups of information‐rich subjects representative samples of the Participants (patients, physians or other stakeholders) population studied described numerically, with Results described in a narrative fashion appropriate statistical measures Types of research data Primar y Data collected primary for the research purpose Secondar y Data useful for drug utilization studies are routinely gathered for Data collected for a different purpose administrative purposes and as Data used secondarily for research part of patient care Electronic health records Administrative & claims data Data used primary for Data used primary for statistical purposes or providing patient care reimbursement Types of data Aggregate Sales data Manufacturer, Wholesaler/distributor data Pharmacy dispensing data Individual -level Health insurance company Pharmacy dispensing data Reimbursement data Electronic health recors Patient registries Surveys  Measurement units drug expenditure weight units number of tablets number of packages number of prescriptions number of DDD (defined daily doses) number of PDD (prescribed daily doses) % patients using the medication ATC/DDD metodology  ATC/DDD methodology Use of the ATC/DDD system represents standardized drug utilization measure to enable comparisons of drug use between countries, regions and other health care settings and to examine trends in drug use over time. Using the system for purposes other that drug utilization can be inappropriate. It is not recommended to base reimbursement and pricing decisions on ATC codes and DDDs DDD: defined daily dose The number of DDDs per package should be calculated for each medicinal product package. Once calculated, this information should be systematically integrated into the national medicinal products registry. DDD (defined daily dose) The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults WHO Collaborating Centre for Drug Statistics DDD units: Methodology  Advantages of DDD Limitations of DDD DDD is a global standardized metric The DDD is nearly always a compromise that provides a fixed unit of based on a review of available measurement information including doses used in various countries when this information ✓ independent of price and is available. currencies DDD does not necessarily reflect the ✓ independent of package size recommended or Prescribed Daily Dose The DDD is sometimes a “dose” that is ✓ independent of strength rarely if ever prescribed, because it DDD allows for the analysis of drug might be an average of two or more commonly used doses. utulization trends and enables comparisons between different DDD does not reflect duration of treatment countries and population groups. Principles of DDD assignment The average adult dose recommended for the main indication as reflected bythe ATC code. When the recommended dose refers to body weight, an adult is considered to be a person of 70 kg. The recommended maintenance dose (long term therapeutic dose) is preferred when establishing the DDD. The initial dose may differ from the maintenance dose but this is not reflected in the DDD. DDDs are not established for topical products, sera, vaccines, antineoplastic agents, allergen extracts, anaesthetics or contrast media. Only one DDD is assigned per ATC code and route of administration Principles of DDD assignment The principle of equipotence: the effect of DDD within the same ATC group should be similar.  DDD is assigned per ATC code and route of administration Same INN → different ATC codes R03: R01: bronchial asthma allergic rhinitis Same ATC→ different routes of administration oral/sublingual route Zdroj: https://atcddd.fhi.no/atc_ddd_index Crohn's disease, ulcerative colitis Examples when the recommended daily dose do not correspond to the DDD: renal impairment metformin DDD: 2000 mg metformin GFR < 45 ml/min: max daily dose: 1000 mg pregabalin GFR < 30 ml/min: max daily dose: 150 mg pregabalin DDD: 300 mg rivaroxaban GFR < 50 ml/min: rivaroxaban DDD: 20 mg max daily dose: 15 mg (indication: atrial fibrilation) age Geriatric dosing: max. dose 0,125 mg according to digoxin DDD: 0,250 mg explicit criteria (AGS Beers criteria) off-label us trazodon for insomnia: 50 - 200 mg trazodon DDD: 300 mg Absolute vs Relative measures Absolute Number of DDD = N packages x N DDD in one package Relative Number of DDD/1000 inhabitants/day N DDD divided by total population per day Number of DDD/100 bed days N DDD divided by number of occupied bed days Relative measures DDD calculation results: aggregate data DDD/1000 inhabitants ATC code N packages N DDD per day folic acid B03BB01 395252 436851375 111,9 colecalciferol A11CC05 1590096 379807253 97,3 rosuvastatin C10AA07 2727798 306726396 78,6 atorvatatin C10AA05 3509218 270116537 69,2 acetylsalicylic acid B01AC06 2773712 224498914 57,5 omeprazol A02BC01 2668743 174398890 44,7 ramipril C09AA05 1822225 172644505 44,2 levothyroxine H03AA01 2719167 154185407 39,5 perindopril C09AA04 1554781 149836030 38,4 amlodipine C08CA01 1432372 130571545 33,5 telmisartan C09CA07 1175892 125458588 32,1 ibuprofen M01AE01 7084935 122577279 31,4  Prescribed daily dose (PDD) The prescribed daily dose (PDD) is the average daily dose prescribed, as obtained from a representative sample of prescriptions Prescribed dosages vary by indication, between individuals and population groups and by health structures and settings For antiinfectives, PDDs may vary according to the severity of the infection and to antibiotic resistance patterns in the area It should be noted that the PDD does not necessarily reflect actual drug consumption. Some prescribed medications are not dispensed, and patients do not always take all the medications they are dispensed  Weight units If we want to study the effect of total drug exposure on the environment, we might measure the use of drugs in weight units (e.g. hormones or hormone-like substances and antimicrobials) in humans, animals and food production Weight in grams can mirror a country’s drug burden For example, if you and can guide health want to measure authorities in their work dermatological against possible adverse products like drug effects on the ointment, lotions population level and the and creams, emergence of weight of drug antimicrobial resistance. formulation may be suitable  Number of packages Number of prescriptions Counting of packages can be used as Counting of prescriptions can be used in the an add‐on measure in studies of evaluation of the clinical use of drugs antibiotic use In Sweden, national targets are set for antibiotic This can be of value in countries were use in outpatients. Numbers of the pack size is fitted to recommended prescriptions/1000 inhabitants, together with course lengths and when there are DDD/1000 inhabitants, are for benchmarking changes in pack size or increases per against targets unit over time. Numbers of prescriptions do not give a good expression of total use unless total amounts of drug per prescription are also considered  Prevalence vs Incidence It is possible to calculate the prevalence or incidence Prevalence when individual–level data = existing users of PPI are available Incidence = new users of PPI Hálfdánarson ÓÖ, Pottegård A, Björnsson ES, et al. Proton-pump inhibitors among adults: a nationwide drug-utilization study. Therap Adv Gastroenterol. 2018  Drug expenditure Pharmaceutical expenditure is medicine price multiplied by volume. manufacturer Different price types related to the various stakeholders: Ex‐factory price wholesaler (distributor) price set at the level of the manufacturer Pharmacy purchasing price (wholesale price) price at the level of the wholesaler; this includes the remuneration for the wholesaler (distributor) Pharmacy retail price price at the level of the pharmacy; this includes the remuneration for the wholesaler and the pharmacist. The pharmacy retail price may be net or gross (including taxes) patient and health Limitations: usually no data on inpatient sector insurance Actual prices might be lower than the list prices, due to discounts, company rebates and various arrangements between the pharmaceutical industry, wholesalers or pharmacies and public payers. Measures according to type of available data Measures applicable with aggregate data Aggregated data, such as reports from manufacturers and distributors, can be Number of packages, Defined Daily used to describe and predict drug Doses (DDD), financial costs consumption and expenditures, or to assess the impact of pharmaceutical policies. Measures requiring individual-level data Individual data (such as electronic health Prevalence – numerator: number of records, patient registries, and health patients exposed insurance databases) can be used to estimate the incidence, prevalence, and Incidence –numerator: number of new duration of medication use, as well as to patients exposed monitor drug utilization patterns over time Usage patterns: switching, persistence,… (e.g. switching)  The use of individual-level data Drug utilization studies facilitate rational use of drugs in the society by documenting who uses and who prescribes drugs, why the drug is prescribed and how it is used, and whether there are differences in drug use over time, between practices, populations, regions, or countries, to compare drug use between populations or countries, or to estimate under- or over-prescribing of a drug in a population. Individual-level drug dispensing data can be used to assess drug combinations (concurrent drug use, polypharmacy, and drug–drug interactions) and switching. Individual-level drug dispensing data can be used to assess prescription drug misuse (proxies:the number of prescribers, the number of pharmacies dispensing the drug, overlapping prescriptions, and the volume of dispensed drug. Rasmussen L, Wettermark B, Steinke D, Pottegård A. Core concepts in pharmacoepidemiology: Measures of drug utilization based on individual-level drug dispensing data. Pharmacoepidemiol Drug Saf. 2022;31(10):1015-1026. doi:10.1002/pds.5490 Data sources  Aggregate vs individual data MAH = Marketing authorisation holder MAH manufacturer (pharmaceutical company) Claims data are generated whenever healthcare providers (including reports from distributors distributor pharmacy) submit a request for Regulatory payment to health insurance companies authority Health insurance pharmacy companies e- prescription surveys Healthcare providers interviews patient electronic health records prescribing data prescribing data patient registries  Sales data Sales data provide information about sales of drugs from manufacturers or wholesalers (distributors) to community and hospital pharmacies. Sales data can also be obtained from pharmacies and nonpharmacy outlets (selected medicinal products). The main data elements collected are the drug name and the amount sold. Advantage: Both prescription and over‐the‐counter (OTC) drugs are usually included in the sales statistics, but it may not be possible to distinguish between the two. Limitation: only aggregate data are available Examples of studies based on sales data include assessment of the impact of pharmaceutical policies and interventions, coss‐national comparisons of drug utilization, forecasting of drug utilization and expenditure Example: IQVIA database  Pharmacy dispensing data Advantages: Pharmacy dispensing databases, unlike the reimbursement data normally register all dispensations of prescription drugs regardless of the drug’s reimbursement status. Electronic health records Historically, patient records were kept in paper form, but in recent decades more and more data have been stored electronically. Today, Electronic health records (EHR) comprise many components that work together to capture, create, share, maintain and store an accurate and complete patient health record Advantages: Health care providers document a wide range of information Limitation: using EHRs for research requires implementation of a system for structured data capture, as well as functions to ensure the accuracy and completeness of data collected. Limitation of both data sources: without national coverage  Reimbursement data Health insurance companies collect funds from the population they cover, and the collected resources are used to reimburse provided healthcare services. Health insurance companies receive claims data for the reimbursement. Limitations: health insurance records lack information on the dispensation of non- reimbursed medications, and the existence of various health insurance companies leads to the existence of different databases with data on drug utilization Health care delivery and financing Health can be simplified as a transfer of Healthcare provider insurance resources: the provider transfers company health care resources to patients, and third‐party payers (health insurance companies) transfer financial resources to the provider.  Patient registries A patient registry is an organized system that collects uniform data to evaluate specified outcomes for a population defined by a particular disease, condition or exposure, and that serves predetermined scientific, clinical or policy purposes Based on the population selection criteria, patient registries can be classified into: disease registries (patients diagnosed with a certain condition, e.g. rheumatoid arthritis) and drug registries (patients exposed to medicinal products, e.g. TNFα inhibitors). Patient registries can be set up and maintained by health care professionals and academic researchers or by manufacturers. Alternatively, post‐marketing registries can be established by regulatory agencies to monitor the appropriateness of prescribing of new drugs (e.g. clozapine registry)  Regulatory Agency In the Czech Republic: State Institute for Drug Control MAH Limitation: only aggregate Regulatory reports from distributors distributor data authority pharmacy MAH = Marketing authorisation holder Record linkage Linking records from different data sources allows a more comprehensive patient and prescriber profile to be built, enabling researchers to study the appropriateness of drug use and factors potentially influencing drug utilization. Record linkage can also help complete drug exposure histories across different health care settings. e.g. scandinavian registries Laugesen K et al. Nordic Health Registry-Based Research: A Review of Health Care Systems and Key Registries. Clin Epidemiol. 2021;13:533-554 Strom BL, Kimmel SE, Hennessy S. Textbook of pharmacoepidemiology. 3rd ed. Hoboken, NJ: Wiley BlackWell, 2021, 528 p. ISBN: 9781119701071  Examples of studies Time‐dependent variations in drug utilization Drug use varies over time for a number of reasons, including normal life cycle changes, emerging safety concerns and interventions from health authorities. Comparison of drug utilization across different geographical areas or different health care settings Comparative studies of patient and prescriber characteristics Drug utilization studies may compare health system factors related to legislation for drug approval, prescribing regulations, drug supply structures, financing models and strategies by which to promote access to essential medicines and the quality use of medicines. Assessment of quality of prescribing using quality indicators  Impact of clinical guidelines Changes in antihypertensive drug prescriptions First-line combination therapy thiazide diuretics beta-blockers Before 2007 ACEi CCB After 2007 Rouette J et al. Treatment and prescribing trends of antihypertensive drugs in 2.7 million UK primary care patients over 31 years: a population- based cohort study. BMJ Open. 2022;12(6):e057510.  Reduction in benzodiazepines prescribing Højlund M, Gudmundsson LS, Andersen JH, et al. Use of benzodiazepines and benzodiazepine-related drugs in the Nordic countries between 2000 and 2020 Basic Clin Pharmacol Toxicol. 2022  Changes in use of glucose-lowering drugs Total drug use per quarter (million DDDs) Total number of users (1,000) Pottegård A, Andersen JH, Søndergaard J, Thomsen RW, Vilsbøll T. Changes in use of glucose-lowering drugs: A Danish nationwide study. Diabetes Obes Metab. 2022. doi: 10.1111/dom.14947 Examples: Impact of published studies Pottegård A, Bech BH, Pedersen SA, Christensen B. Use of hydrochlorothiazide in Denmark following publication of skin cancer risk findings. Pharmacoepidemiol Drug Saf. 2021;30(11):1611-1616. RALES study publication and spironolactone prescription RALES = Randomized Aldactone Evaluation Study Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351(6):543- 551.  Example: Impact of COVID-19 pandemic an increase in rates of psychotropic treatment during the COVID-19 pandemic in children PSYCHOTROPIC MEDICATIONS: antipsychotics (NO5A), anxiolytics (N05B) , hypnotics and sedatives (N05C), antidepressants (N06A), psychostimulants (N06B) Bliddal M, Rasmussen L, Andersen JH, Jensen PB, Pottegård A, Munk-Olsen T, Kildegaard H, Wesselhoeft R. Psychotropic Medication Use and Psychiatric Disorders During the COVID-19 Pandemic Among Danish Children, Adolescents, and Young Adults. JAMA Psychiatry. 2022  Example: Impact of regulatory actions valproate dextropropoxyphene Impact of Risk Minimisation Measures in Pharmacovigilance Following the European Union's 2018 measures to minimize the teratogenicity associated with valproate, a significant decrease in valproate consumption among women of fertile age was observed Abtahi S et al. Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Elseviers M et al. Drug Utilization Research: Methods and Applications. 1st ed. Prescribing Trends of Medicinal Products Containing Valproate: An Chichester, West Sussex: John Wiley & Sons Ltd; 2016. ISBN: 978-1-118-94978-8 Interrupted Time Series Study. Drug Saf. 2023;46(7):689-702.  Example from Czechia: anticoagulantants DOAC utilization has been steadily increasing since their introduction to the market Maly J, Dvorackova S, Zimcikova E, Kubena AA, Kolar J, Vlcek J, Penka M, Mala-Ladova K. Patterns in anticoagulant utilization in the Czech Republic during 2007-2017. J Thromb Thrombolysis. 2019;47(2):305-311  Drug Utilization Drug utilization = drug exposition in a given population, in a given time/period, and in a certain socioeconomic environment Drug Utilization Research is a discipline dedicated to the analysis and assessment of prescribing, dispensing and consumption of medications Aim: facilitate rational use of medicines Significance: monitoring the impacts of regulatory measures and health policy changes, (e.g.changes in prices and reimbursements, pharmacovigilance risk minimization measures), marketing strategies, studying drug utilization in specific populations and therapeutic areas, assessment of the quality of medicine use, pharmacoepidemiology research: exposure to a given medication, pharmacoeconomic analyses, estimation of disease prevalence Drug utilization may be expressed in various measures: weight units, number of packages, number of prescriptions, number of prescribed daily doses (PDDs), number of defined daily doses (DDDs), proportion of patients taking the medication, drug expenditure  Drug Utilization: measurement Defined daily dose (DDD) is a global standardized metric that provides a fixed unit of measurement independent of price, currencies, package size and strength. DDD enables comparisons between different countries and population groups. DDD is defined as the asummed average maintenance dose of the drug when used on its major indication in adults. ATC/DDD index is published on the website of the WHO Collaborating Centre for Drug Statistics Methodology. Only one DDD is assigned per ATC code and route of administration The Defined daily dose (DDD) does not necessarily reflect the recommended or Prescribed Daily Dose. Therapeutic doses for individual patients and patient groups will often differ from the DDD as they will be based on individual characteristics, such as age, weight, kidney functions, ethnic differences, type and severity of disease, pharmacokinetic considerations or unapproved use of medication (off-label use).  Drug Utilization: data sources Data sources in drug utilization research include sales data (from manufacturers and distributors), pharmacy dispensing data, electronic health records, reimbursement data from health insurance companies, patient registries, regulatory agency Drug regulatory agency in the Czech Republic - State Institute for Drug Control (SÚKL) has access to aggregated data on drug utilization based on reports from manucfacturers, distributors and pharmacies, offering full population coverage. Reimbursement data (health insurance companies): provide individual-level data, but only for reimbursed medications. The existence of multiple health insurance companies leads to incomplete population coverage. Electronic health records: If only unstructured data are available, analysis potential is limited. Aggregate vs Individual-level data: Aggregated data (e.g. from manufacturers and distributors) can predict drug utilization and assess pharmaceutical policy impacts, while individual data (electronic health records and reimbursement data) help analyze changes in medication use patterns, duration of medication use and calculate prevalence and incidence, of medication use Sources Elseviers M et al (eds.) Drug Utilization Research: Methods and Applications. First Edition. John Wiley & Sons Ltd; 2016. Strom BL, Kimmel SE, Hennessy S (eds.) Pharmacoepidemiology. Sixth Edition. John Wiley & Sons Ltd; 2020 Doug Steinke, Lisa Pont, Bjorn Wettermark, Katja Taxis, Lisa Kalisch Ellett, Petra Denig. Overview and Essential Methods of Drug Utilization Research. International Conference on Pharmacoepidemiology and Therapeutic Risk Management - ICPE All Access 2020 (Special Session Skills Course) Copyright and fair use This lecture reproduced copyrighted material. Fair use allows limited use of copyrighted material without permission from the copyright holder for the purpose of teaching. You are strictly prohibited from sharing the material with others in general and from posting the material on the Web or other file sharing venues in particular. You may only make copies of course materials for your own use.