The Digitalization of medicine supply chain: How to re-aim the shots in the dark?

ABSTRACT Healthcare expenses have been on the rise for decades. One of the key areas contributing to this ever-expanding growth is medicine expenses. Medicines are required to maintain a sustainable health system in a world of aging populations and pandemics. Novel medicines combat diseases previously considered incurable, and medicines help people with chronic conditions to live normal lives. Furthermore, in emerging economies, pharmacies are often the first and only interface to healthcare services, whereby other medical services are scarce or expensive. However, medicines are associated with costs. To maintain a sustainable health system, the growing expenses have to be managed. There are different ways of controlling medicine expenses. In this age of digitalization, when multiple sectors have been disrupted by digital technologies, it can be argued that digital technologies have a role to play in the medicine supply field. This intersection of medicine supply and information systems has been, however, sparsely studied. This thesis seeks to fill this research gap by exploring the medicine supply chain and discovering obstacles and bottlenecks across the chain. The study also intends to identify how information systems and digital technologies can be utilized to remediate the problems and facilitate an efficient medicine supply chain. The research approaches the medicine supply chain arena through the medicine supply chain concept. The supply chain is a highly complex world involving the pharmaceutical industry and the distribution, prescription and dispensing of medicines. This research examines this arena through cases from across the supply chain covered in four separate studies and related articles. The supply chain concept and the scene are set in one of the studies, followed by studies on the digitalization of pharmacies, medicine waste management in hospitals and the digitalization of the plasma derivatives supply chain. The results of this research illustrate that the main role of digital technology in the management of the medicine supply chain relates to managing several information asymmetries across the chain. The key is to increase transparency between various stakeholders in the chain through novel digital solutions. Currently, the supply chain processes are largely based on rules of thumb rather than facts and evidence, and this should be addressed to maintain a sustainable chain and, subsequently, a sustainable health system. TIIVISTELMÄ Terveydenhuollon kulut ovat nousseet vuosikymmenien ajan. Lääkekulut muodostavat merkittävän osan terveysmenoista. Lääkkeitä tarvitaan kestävän terveydenhuoltojärjestelmän ylläpitämiseksi: lääkkeillä voidaan hoitaa aiemmin parantumattomia sairauksia sekä tukea ikääntyvää väestöä. Kehittyvissä talouksissa apteekit ovat usein myös ensimmäinen ja ainoa yhteys terveyspalveluihin. Lääkkeillä ja niiden kehittämisellä on kuitenkin kulunsa ja kestävän terveydenhuollon järjestelmän ylläpitämiseksi onkin kyettävä ymmärtämään ja hallitsemaan lääkekuluja. Lääkekuluja voidaan hallita eri tavoin. Digitalisaatiolla voidaan ajatella olevan tässä myös roolinsa – useat toimialathan ovat muuttuneet merkittävästi digitaalisten ratkaisujen myötä. Digitalisaation ja tietojärjestelmien merkitystä lääkejakelussa ei olla kuitenkaan tutkittu laajasti. Tämän väitöskirjan tarkoituksena on täyttää tätä tutkimusaukkoa perehtyen lääkejakelun prosesseihin, niihin liittyviin esteisiin ja pullonkauloihin sekä digitaalisiin ratkaisuihin, joilla lääkejakelua voidaan tukea ja tehostaa. Tutkimus lähestyy aluetta mallintaen lääkejakeluketjua. Lääkejakeluketju on monimutkainen globaali systeemi, joka kattaa toimijoita mm. lääketeollisuudesta, jakelusta ja logistiikasta, terveydenhuollosta ja vähittäismyynnistä. Tässä tutkimuksessa jakeluketjua tarkastellaan neljän tutkimuksen kautta, jotka liittyvät lääkejakeluketjun eri osiin. Aluksi esitellään lääkejakeluketjukonsepti, jota seuraavat tutkimukset apteekkien digitalisoinnista, sairaalan lääkehuollosta ja veriplasmatuotteiden toimitusketjun digitalisoinnista. Tämän tutkimuksen tulokset havainnollistavat, että digitaalisten ratkaisujen päärooli lääkejakeluketjun hallinnassa liittyy varsinkin informaatiosymmetrioiden hallintaan sekä tiedon avoimuuden ja läpinäkyvyyden lisäämiseen ketjun eri sidosryhmien välillä. Nykyisin lääkejakeluketjun prosesseja leimaa epävarmuus ja faktoihin perustuva päätöksenteko on vaikeaa, mikä heikentää tehokkaan lääkejakelun ylläpitämistä

Eliminating medicine waste in a Finnish university hospital — a qualitative study

Background:Medicine waste in hospitals leads to severe economic loss. This waste emerges for a number of reasons. Medicines are often ordered in too large quantities, which leads to stock expiring without being dispensed.Wastage can also be a consequence of poor management practices. Technical aids, such as automatic dispensers,have been suggested to reduce waste, but they too have shortcomings. Information systems can arguably contribute to waste reduction, but this area has not been widely researched.In this exploratory case study, we scrutinized the management of medicines waste in a hospital from an information systems perspective and examined how information systems are used to manage the medicine supply chain and medicine waste. Our research case was a Finnish university hospital, its central pharmacy, and, more widely, the medicine supply chain within the hospital.Methods:This is a qualitative case study, based on data gathered through interviews and a survey and a review of other information sources, including annual reports and other relevant collateral. The study participants included pharmacy staff members and other hospital staff involved in medicine supply. The interviews were conducted in two rounds, first capturing the main themes and then exploring them further in the later study stages.Results:The findings outline a picture of unfit technology and inconsistent and unreliable information. This is compensated for by manual practices and processes that cause an excessive administrative burden and ultimately increased wastage. An infrequent ordering process combined with the lack of recycling practices increase the wastage even more.Conclusion:Medicine supply and waste management remain a manual administrative task. Inconsistent information and unfit information systems make this task challenging, and the process relies on the medicine supply staff’s experience and assumptions.</p

Electronic prescription as a driver for digitalization in Finnish pharmacies

BackgroundFinnish community pharmacies have undergone digitalization during the past decade. The introduction of the electronic prescription has had a significant impact on pharmacy workflows, such as the dispensing process. This inevitably has significant sociotechnical implications. We examine the impact of digitalization on the dispensing process and the sociotechnical orientation of a pharmacy.MethodsWe utilize data collected in customer service situations in Finnish community pharmacies at two points in time: in the traditional workflow, when electronic prescriptions were not in use, and in the new direct dispensing workflow, which is the usual delivery model in the case of electronic prescriptions. We analyze this data in terms of changes in workflow efficiency. We also draw on existing literature to build a conceptual model for digitalization in the pharmacy sector from a sociotechnical standpoint.ResultsIn the Finnish environment, the results, based on our study sample, show that with electronic prescriptions and the direct dispensing model, the delivery time for a single medication over the counter was reduced by 13%. The results also indicate that the process has become more predictable, as the variation in terms of the workflow lead time has decreased.ConclusionsThe results indicate that the dispensing process has become more efficient in terms of time and throughput as well as more technically oriented and predictable. From a sociotechnical perspective, the results indicate that the technical subsystem has strengthened, and pharmacies have adapted to the new technology in the dispensing process.</p

Intelligent Physical Robots in Health Care: Systematic Literature Review

Background: Intelligent physical robots based on artificial intelligence have been argued to bring about dramatic changes in health care services. Previous research has examined the use of intelligent physical robots in the health care context from different perspectives; however, an overview of the antecedents and consequences of intelligent physical robot use in health care is lacking in the literature. Objective: In this paper, we aimed to provide an overview of the antecedents and consequences of intelligent physical robot use in health care and to propose potential agendas for future research through a systematic literature review. Methods: We conducted a systematic literature review on intelligent physical robots in the health care field following the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Literature searches were conducted in 5 databases (PubMed, Scopus, PsycINFO, Embase, and CINAHL) in May 2021, focusing on studies using intelligent physical robots for health care purposes. Subsequently, the quality of the included studies was assessed using the Mixed Methods Appraisal Tool. We performed an exploratory content analysis and synthesized the findings extracted from the included articles. Results: A total of 94 research articles were included in the review. Intelligent physical robots, including mechanoid, humanoid, android, and animalistic robots, have been used in hospitals, nursing homes, mental health care centers, laboratories, and patients’ homes by both end customers and health care professionals. The antecedents for intelligent physical robot use are categorized into individual-, organization-, and robot-related factors. Intelligent physical robot use in the health care context leads to both non–health-related consequences (emotional outcomes, attitude and evaluation outcomes, and behavioral outcomes) and consequences for (physical, mental, and social) health promotion for individual users. Accordingly, an integrative framework was proposed to obtain an overview of the antecedents and consequences of intelligent physical robot use in the health care context. Conclusions: This study contributes to the literature by summarizing current knowledge in the field of intelligent physical robot use in health care, by identifying the antecedents and the consequences of intelligent physical robot use, and by proposing potential future research agendas in the specific area based on the research findings in the literature and the identified knowledge gaps.publishedVersionPeer reviewe

Semimechanistic Population Pharmacokinetic Model to Predict the Drug-Drug Interaction Between S-ketamine and Ticlopidine in Healthy Human Volunteers

Low-dose oral S-ketamine is increasingly used in chronic pain therapy, but extensive cytochrome P450 (CYP) mediated metabolism makes it prone to pharmacokinetic drug-drug interactions (DDIs). In our study, concentration-time data from five studies were used to develop a semimechanistic model that describes the ticlopidine-mediated inhibition of S-ketamine biotransformation. A mechanistic model was implemented to account for reversible and time-dependent hepatic CYP2B6 inactivation by ticlopidine, which causes elevated S-ketamine exposure in vivo. A pharmacokinetic model was developed with gut wall and hepatic clearances for S-ketamine, its primary metabolite norketamine, and ticlopidine. Nonlinear mixed effects modeling approach was used (NONMEM version 7.3.0), and the final model was evaluated with visual predictive checks and the sampling-importance-resampling procedure. Our final model produces biologically plausible output and demonstrates that ticlopidine is a strong inhibitor of CYP2B6 mediated S-ketamine metabolism. Simulations from our model may be used to evaluate chronic pain therapy with S-ketamine.Peer reviewe

Semimechanistic Population Pharmacokinetic Model to Predict the Drug–Drug Interaction Between S-ketamine and Ticlopidine in Healthy Human Volunteers

Low‐dose oral S‐ketamine is increasingly used in chronic pain therapy, but extensive cytochrome P450 (CYP) mediated metabolism makes it prone to pharmacokinetic drug‐drug interactions (DDIs). In our study, concentration‐time data from five studies were used to develop a semimechanistic model that describes the ticlopidine‐mediated inhibition of S‐ketamine biotransformation. A mechanistic model was implemented to account for reversible and time‐dependent hepatic CYP2B6 inactivation by ticlopidine, which causes elevated S‐ketamine exposure in vivo. A pharmacokinetic model was developed with gut wall and hepatic clearances for S‐ketamine, its primary metabolite norketamine, and ticlopidine. Nonlinear mixed effects modeling approach was used (NONMEM version 7.3.0), and the final model was evaluated with visual predictive checks and the sampling‐importance‐resampling procedure. Our final model produces biologically plausible output and demonstrates that ticlopidine is a strong inhibitor of CYP2B6 mediated S‐ketamine metabolism. Simulations from our model may be used to evaluate chronic pain therapy with S‐ketamine.</p

Relationship of Edoxaban Plasma Concentration and Blood Coagulation in Healthy Volunteers Using Standard Laboratory Tests and Viscoelastic Analysis

The capability of viscoelastic measurement parameters to screen anticoagulation activity of edoxaban in relation to its plasma concentrations was evaluated in 15 healthy male volunteers. Blood samples were drawn before the oral administration of edoxaban 60 mg and 2, 4, 6, 8, and 24 hours after administration. At each time, standard coagulation tests were performed, blood viscoelastic properties were measured with a thromboelastometry device ROTEM delta analyzer (Instrumentation Laboratory, Werfen, Barcelona, Spain), and edoxaban plasma concentrations were measured. Our primary interest was the possible correlation between edoxaban plasma concentrations and values for ROTEM ExTEM, and FibTEM. We also studied the correlation of edoxaban plasma concentrations with the results of standard coagulation tests. We saw the effect of a single dose of edoxaban most clearly in clotting time (CT) of ROTEM ExTEM and FibTEM. Changes in these parameters correlated significantly with edoxaban plasma concentrations up to 6 hours from the ingestion of the drug. Activated partial thromboplastin time, prothrombin time, and anti-factor Xa were also affected. Peak changes were observed 2 and 4 hours after administration of edoxaban. The changes were mostly reversed after 8 hours. In conclusion, ROTEM CT correlates significantly with edoxaban plasma concentrations and can be used to estimate the effect of edoxaban. ROTEM should be considered as part of the assessment of coagulation, with the big advantage of being readily available on site

S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: A randomized, double-blind, placebo-controlled clinical trial

Background Spinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative opioid consumption is still unknown.Methods We randomized 107 patients at two tertiary hospitals in a double-blinded, placebo-controlled clinical trial of adults undergoing major lumbar spinal fusion surgery. Patients were randomly allocated to four groups in order to compare the effects of three different doses of adjunct S-ketamine (0.25, 0.5, and 0.75 mg ml-1) or placebo on postoperative analgesia in oxycodone PCA. Study drugs were administered for 24 hours postoperative after which oxycodone-PCA was continued for further 48 hours. Our primary outcome was cumulative oxycodone consumption at 24 hours after surgery.Results Of the 100 patients analyzed, patients receiving 0.75 mg ml(-1) S-ketamine in oxycodone PCA needed 25% less oxycodone at 24 h postoperatively (61.2 mg) compared with patients receiving 0.5 mg ml(-1) (74.7 mg) or 0.25 mg ml(-1) (74.1 mg) S-ketamine in oxycodone or oxycodone alone (81.9 mg) (mean difference: -20.6 mg; 95% confidence interval [CI]: -41 to -0.20; P = 0.048). A beneficial effect in mean change of pain intensity at rest was seen in the group receiving 0.75 mg ml(-1) S-ketamine in oxycodone PCA compared with patients receiving lower ketamine doses or oxycodone alone (standardized effect size: 0.17, 95% CI: 0.013-0.32, P = 0.033). The occurrence of adverse events was similar among the groups.Conclusions Oxycodone PCA containing S-ketamine as an adjunct at a ratio of 1: 0.75 decreased cumulative oxycodone consumption at 24 h after major lumbar spinal fusion surgery without additional adverse effects