Clinical guidelines carry medical evidence to the point of practice. As evidence is not always available, many guidelines do not provide recommendations for all clinical situations encountered in ...practice. We propose an approach for identifying knowledge gaps in guidelines and for exploring physicians' therapeutic decisions with data mining techniques to fill these knowledge gaps. We demonstrate our method by an example in the domain of type 2 diabetes.
We analyzed the French national guidelines for the management of type 2 diabetes to identify clinical conditions that are not covered or those for which the guidelines do not provide recommendations. We extracted patient records corresponding to each clinical condition from a database of type 2 diabetic patients treated at Avicenne University Hospital of Bobigny, France. We explored physicians' prescriptions for each of these profiles using C5.0 decision-tree learning algorithm. We developed decision-trees for different levels of detail of the therapeutic decision, namely the type of treatment, the pharmaco-therapeutic class, the international non proprietary name, and the dose of each medication. We compared the rules generated with those added to the guidelines in a newer version, to examine their similarity.
We extracted 27 rules from the analysis of a database of 463 patient records. Eleven rules were about the choice of the type of treatment and thirteen rules about the choice of the pharmaco-therapeutic class of each drug. For the choice of the international non proprietary name and the dose, we could extract only a few rules because the number of patient records was too low for these factors. The extracted rules showed similarities with those added to the newer version of the guidelines.
Our method showed its usefulness for completing guidelines recommendations with rules learnt automatically from physicians' prescriptions. It could be used during the development of guidelines as a complementary source from practice-based knowledge. It can also be used as an evaluation tool for comparing a physician's therapeutic decisions with those recommended by a given set of clinical guidelines. The example we described showed that physician practice was in some ways ahead of the guideline.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
To determine the effectiveness of risk minimisation measures (RMM) to avoid inadvertent daily instead of weekly methotrexate (MTX) use, introduced by the European Medicines Agency (EMA) from ...2019 onwards.
Methods
Using a cross‐sectional online survey in France, Greece, Germany, Poland, and Sweden in 2022, we assessed awareness, knowledge, and self‐declared behaviour for respondents who prescribed, dispensed, or used once‐weekly MTX in the last 3 months. Respondents' answers were considered as ‘successful’ with regards to RMM effectiveness (vs. unsuccessful) if they provided correct (‘desirable’) responses to 100% of questions regarding awareness and self‐declared behaviour and correct responses to ≥80% of questions about knowledge. Per target population, an outcome was considered successful if achieved by ≥80% of respondents. Effectiveness of RMM was defined by ≥80% being successful on all outcomes.
Results
One‐hundred‐fifty‐one prescribers, 150 pharmacists, and 150 patients completed the survey. Success rates were 56% (95% CI 48.0%–64.3%) for awareness, 42% (95% CI 34.4%–50.7%) for knowledge, and 31% (95% CI 23.8%–39.2%) for self‐declared behaviour among prescribers, 18% (95% CI 12.8%–25.8%) for awareness, 7% (95% CI 3.7%–12.7%) for knowledge, and 50% (95% CI 41.7%–58.3%) for self‐declared behaviour among pharmacists, and 29% (95% CI 21.6%–36.6%) for awareness, and 3% (95% CI 1.1%–7.6%) for knowledge among patients. Overall success was not attained by any target population.
Conclusions
RMM were evaluated as not effective across outcomes of awareness, knowledge, and self‐declared behaviour in prescribers, pharmacists, and patients. Findings suggested we need continued efforts for RMM across all target populations and across all outcomes.
Introduction
Hypersensitivity reactions (HSRs) are among the known adverse events of intravenous (i.v.) iron products. Of these, particularly severe HSRs such as anaphylaxis are of great clinical ...concern due to their life-threatening potential.
Methods
This was a retrospective pharmacoepidemiological study with a case-population design evaluating the number of reported severe HSRs following administration of the two i.v. iron products—ferric carboxymaltose and iron (III) isomaltoside 1000—in relation to exposure in European countries from January 2014 to December 2017. Exposure to both products was estimated using IQVIA MIDAS sales data in European countries. Information on spontaneously reported severe HSRs was obtained from and analysed separately for the two established safety surveillance databases EudraVigilance and VigiBase™ using the MedDRA
®
Preferred Terms
anaphylactic reaction
,
anaphylactic shock
,
anaphylactoid reaction
and
anaphylactoid shock
associated with administration of either product.
Results
Between 2014 and 2017, the reporting rate of severe HSRs per 100,000 defined daily doses (100 mg dose equivalents of iron) varied from 0.3 to 0.5 for ferric carboxymaltose and from 2.4 to 5.0 for iron (III) isomaltoside 1000. The reporting rate ratio for iron (III) isomaltoside 1000 versus ferric carboxymaltose was between 5.6 (95% CI 3.5–9.0) and 16.2 (95% CI 9.4–27.8).
Conclusions
Findings suggest that iron (III) isomaltoside 1000 is associated with a higher reporting rate of severe HSRs related to estimated exposure than ferric carboxymaltose in European countries. Future research investigating the occurrence of severe HSRs associated with i.v. ferric carboxymaltose and iron (III) isomaltoside 1000 is needed to broaden the evidence for benefit-risk assessment.
Purpose
The purpose of this study was to evaluate the effectiveness of the risk minimisation measures (RMMs) implemented in Europe in 2014 for valproate‐containing products to mitigate their risk ...during pregnancy and to characterise valproate prescribing patterns in women of childbearing potential (WCBP) before and after implementation of RMMs.
Methods
A multinational cohort study based on existing data sources using a pre‐/post‐ design was performed in five European countries (France, Germany, Spain, Sweden, UK) in an outpatient setting. Effectiveness of RMMs was assessed by comparing the proportion of valproate initiations as second (or subsequent) line therapy before and after implementation of RMMs (primary outcome) with an increase in this proportion indicating success of RMMs. Overall use of valproate and incidence of pregnancies in WCBP were also examined.
Results
The proportion of valproate initiations as second line therapy increased after implementation of RMMs in incident female users in Sweden (from 81.1%, 95% CI 79.9%‐82.3% to 84.5%, 95% CI 83.5%‐85.5%) and the UK (from 66.4%, 95% CI 64.5%‐68.3% to 72.4%, 95% CI 70.0%‐74.9%), it remained the same in Germany and Spain and decreased in France from 48.7% (95% CI 45.6%‐51.9%) to 40.6% (95% CI 37.6%‐43.7%). In Sweden and the UK, the incidence of pregnancies exposed to valproate decreased in the post‐implementation period: 8.0 vs 9.5 and 10.9 vs 16.9 per 1000 person‐years, respectively.
Conclusion
The results on primary outcome of this study suggest limited effectiveness of the RMMs. Additional RMMs were implemented in 2018.
Since 2014, valproate has not been recommended for use in girls and women of childbearing potential unless other treatments are ineffective or not tolerated. Risk minimization measures (RMMs) of ...valproate were implemented to reduce the potential risks of developmental disorders among pregnant women. A drug utilization study was carried out to assess the effectiveness of RMMs.
This was a multinational, non-interventional cohort study. For the UK, existing data from the Clinical Practice Research Datalink database were used. The primary study endpoint was a change in the proportion of valproate initiations preceded by other medications relevant for valproate indications before and after implementation of RMMs.
The proportion of valproate initiations preceded by medications related to valproate indications increased after RMM implementation in incident female users in the UK from 66.4% to 72.4%. The proportion of incident prescriptions for epilepsy and bipolar disorder with prior medication related to valproate indications increased, from 36.2% to 44.1% and 72.9% to 77.8%, respectively. The incidence rate of valproate-exposed pregnancies decreased from 16.9 to 10.9 per 1000 person-years in the pre- and post-implementation periods, respectively.
Results from this study indicated some improvement in physician prescribing and a potential reduction in valproate-exposed pregnancies in the UK. Given only modest improvement has been achieved, additional RMMs were implemented in 2018.
Purpose
We evaluated the effectiveness of additional risk minimisation measures (aRMMs; i.e., educational materials) distributed to prescribers to ensure that only individuals with evidence of prior ...dengue infection (PDI, i.e., dengue seropositive) would be vaccinated with the tetravalent dengue vaccine (CYD‐TDV; Dengvaxia®).
Methods
A survey was conducted in 2020 among 300 CYD‐TDV prescribers in Brazil and Thailand to ascertain three success criteria: prescribers' awareness of the materials (receiving and reading them); knowledge of the key messages; and whether their self‐reported behaviour regarding practice‐related scenarios was aligned with the updated guidance.
Results
The aRMMs were not generally effective as <80% of prescribers in both countries met two of the three predefined success criteria. In Brazil, 98.7% were aware of the aRMMs whereas in Thailand this criterion was fulfilled by 74.0%. Almost all prescribers knew that CYD‐TDV was recommended only in individuals with PDI (98.7% and 96.7% in Brazil and Thailand, respectively). In Brazil, where vaccination was restricted to those with a documented history of PDI, 11.3% considered that confirmation should be done through a blood test. More than 75% in both countries considered additional signs of dengue, as early warning signs, and not only those regarded as such by the 2009 WHO guidelines.
Conclusions
These results do not support that the aRMMs were effective as the predefined success criteria were not met. The use of reliable rapid diagnosis tests together with the revised prescribing information and educational materials will facilitate the implementation and compliance with pre‐vaccination screening for CYD‐TDV eligibility.
As part of the risk management plan in Europe, this study was conducted to characterize drug utilization patterns of Seasonique, a 91 day extended levonorgestrel-containing combined oral ...contraceptive (COC
LNG
).
A retrospective observational study was conducted in France, Italy and Belgium using electronic medical record databases obtained from general practitioners (GPs) in all participating countries and gynecologists in France from 2015 to 2018. The study population included women receiving ≥1 prescription of 91 day COC
LNG
during the study period. Prescribing patterns of 91 day COC
LNG
were examined including: (1) treatment duration; (2) indication; (3) use of combined oral contraceptive (COC) before 91 day COC
LNG
initiation; and (4) switch from and to combined hormonal contraceptives (CHCs) or other contraceptives.
Totals of 235, 220, 207 and 659 women using 91 day COC
LNG
were identified in French, Italian and Belgian GP, and French gynecologist databases, respectively. Across databases, 46-76% of women were prescribed a single 91 day COC
LNG
prescription and median treatment duration ranged from 3 to 6 months. The most common indication was contraception (42-81%), followed by menstrual migraines (2-14%). Use of COC during the 6 months prior to 91 day COC
LNG
initiation was 14% across GP databases, but was lower (8%) in the French gynecologist database. The frequency of switching from 91 day COC
LNG
to CHCs or other contraceptives was generally low (5-12%), with the highest proportion being among patients of French gynecologists.
Findings indicate that 91 day COC
LNG
was prescribed for relatively short durations and predominantly as indicated for contraception. Most results were comparable across all participating countries.
KEY POINTS
Findings from this drug utilization study in European databases across general practitioners and French gynecologists confirmed that 91 day extended levonorgestrel-containing combined oral contraceptive (COC
LNG
) was prescribed for relatively short durations (median 3-6 months); predominantly for the intended indication of contraception.
Combined oral contraceptive use during the 6 months prior to 91 day COC
LNG
initiation, and switching from 91 day COC
LNG
to combined hormonal contraceptives or other contraceptives, were generally low (14% or less).
These findings were mostly consistent across participating countries.
Diabetic type 1 patients are often advised to use dose adjustment guidelines to calculate their doses of insulin. Conventional methods of measuring patients' adherence are not applicable to these ...cases, because insulin doses are not determined in advance. We propose a method and a number of indicators to measure patients' conformance to these insulin dosing guidelines.
We used a database of logbooks of type 1 diabetic patients who participated in a summer camp. Patients used a guideline to calculate the doses of insulin lispro and glargine four times a day, and registered their injected doses in the database. We implemented the guideline in a computer system to calculate recommended doses. We then compared injected and recommended doses by using five indicators that we designed for this purpose: absolute agreement (AA): the two doses are the same; relative agreement (RA): there is a slight difference between them; extreme disagreement (ED): the administered and recommended doses are merely opposite; Under-treatment (UT) and over-treatment (OT): the injected dose is not enough or too high, respectively. We used weighted linear regression model to study the evolution of these indicators over time.
We analyzed 1656 insulin doses injected by 28 patients during a three weeks camp. Overall indicator rates were AA = 45%, RA = 30%, ED = 2%, UT = 26% and OT = 30%. The highest rate of absolute agreement is obtained for insulin glargine (AA = 70%). One patient with alarming behavior (AA = 29%, RA = 24% and ED = 8%) was detected. The monitoring of these indicators over time revealed a crescendo curve of adherence rate which fitted well in a weighted linear model (slope = 0.85, significance = 0.002). This shows an improvement in the quality of therapeutic decision-making of patients during the camp.
Our method allowed the measurement of patients' adherence to their insulin adjustment guidelines. The indicators that we introduced were capable of providing quantitative data on the quality of patients' decision-making for the studied population as a whole, for each individual patient, for all injections, and for each time of injection separately. They can be implemented in monitoring systems to detect non-adherent patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Daratumumab, a monoclonal antibody targeting CD38, is approved to treat multiple myeloma. Red blood cells express low levels of CD38, which can result in a false-positive antibody screen ...in daratumumab-treated patients. Educational materials were developed to inform healthcare professionals (HCPs) and blood transfusion management department personnel (BTMDP) about this risk and recommended measures to mitigate that risk. Materials were distributed in European countries where daratumumab was commercially available. This post-authorization safety study was designed to evaluate whether HCPs and BTMDP understood the materials.
Methods
An anonymous, cross-sectional, non-interventional, web-based survey was distributed in 12 European countries. Four key questions were identified, for which a correct answer from at least 80% of respondents was considered indicative of satisfactory effectiveness.
Results
A total of 408 participants completed the questionnaires (62.3% (
n
= 254) HCPs and 37.7% (
n
= 154) BTMDP). Responses were consistent between groups. All respondents were aware of the educational materials (the first key question) and at least 80% correctly answered three of the four key questions. A key question regarding which blood typing test(s) daratumumab interferes with did not achieve satisfactory effectiveness (60% correct responses). In a weighted analysis, 79% of respondents correctly identified the recommended measures for daratumumab-treated patients requiring transfusion. This was attributed to an error in the survey’s German translation; in a sensitivity analysis, 90% of participants correctly responded to this question.
Conclusions
Results suggest that participants were aware of the educational materials, the risk of daratumumab interference with blood testing, and recommended measures to mitigate that risk.
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