Direct Healthcare Professional Communications Research Articles

Changes in the Use of Hydrochlorothiazide and Other Antihypertensive Drugs in Switzerland in Association With the Swissmedic Safety Alert Regarding Non-melanoma Skin Cancer: An Interrupted Time-Series Analysis Using Swiss Claims Data.

Long-term use of hydrochlorothiazide increases the risk of non-melanoma skin cancer. We aimed to evaluate potential changes in the use of hydrochlorothiazide in Switzerland after a direct healthcare professional communication (DHPC) in November 2018 by Swissmedic. We performed interrupted time-series analyses using a large Swiss healthcare claims database (2015-2021). Within monthly intervals, we quantified the total number of claims and the total dispensed 'defined daily doses' (DDD) for preparations containing (1) hydrochlorothiazide, (2) angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II-receptor blockers (ARB), (3) calcium-channel blockers (CCB) and (4) thiazide-like diuretics per 10 000 persons. Using segmented linear regression, we quantified the pre-DHPC trend, the immediate change and the post-DHPC change in trend for total claims and DDD for the four drug classes weighted for the demographic distribution of the Swiss population. ACE inhibitors and ARB were the most frequently claimed antihypertensive drugs with 300-400 claims per 10 000 persons, which increased by 5.4% during the study period. The average number of hydrochlorothiazide claims (157/10 000 persons in 2015) declined by 35% between 2015 and 2021. The decrease started prior to the DHPC, but the DHPC was associated with an immediate 6.1% decline and an accelerated decline in claims over time after the DHPC (similar results for DDD). This coincided with a 23% increase in claims of CCB (dihydropyridine type) over 7 years, whereas use of other antihypertensives increased less. Our results suggest that the DHPC by Swissmedic in 2018 accelerated a pre-existing decline in the use of hydrochlorothiazide in Switzerland.

Physician Awareness of the Safe Use of Cyproterone Acetate in Europe: A Survey on the Effectiveness of Additional Risk Minimization Measures.

Cyproterone acetate (CPA) is a synthetic progesterone derivative introduced in the 1970s and prescribed as antiandrogenic therapy for inoperable prostate cancer, sexual deviations in men, and signs of androgenization in women. In 2020, the CPA summary of product characteristics (SmPC)was revised to include an updated special warning and precaution about (1) the risk of meningioma with increasing cumulative dose and (2) contraindication in patients with meningioma or history of meningioma. A Direct Healthcare Professional Communication(DHPC) was distributed. The European Medicine Agency's Pharmacovigilance Risk Assessment Committee requested that marketing authorization holders in Europe conduct a survey to assess physicians' knowledge of the updated key safety information. The primary objective of this study was to measure physicians' awareness (i.e., did they receive and review the revised SmPC and DHPC) and level of knowledge and understanding of the key safety information pertaining to the restricted use of CPA monotherapy because of the risk of meningioma. This cross-sectional web-based survey was administered to dermatologists, endocrinologists, gynecologists, urologists, oncologists, psychiatrists, and general practitioners in France, Germany, Poland, Spain, and the Netherlands who had prescribed CPA monotherapy in the previous 12 months to assess awareness of the risk of meningioma associated with CPA monotherapy. Of the 613 physicians who participated, 85% correctly indicated that CPA monotherapy should be prescribed with the lowest effective dose, 75% correctly indicated that the risk of meningioma increases with increasing cumulative CPA monotherapy doses, and 73% correctly indicated that treatment with CPA-containing products must be stopped permanently if a patient is diagnosed with meningioma. Overall, 40% of physicians reported having received the DHPC, and 42% reported having received the revised SmPC. Despite low recall of receipt of the updated SmPC and DHPC, most physicians surveyed are aware of the meningioma risk and actions to mitigate the risk.

What Factors Make EU Regulators Want to Communicate Drug Safety Issues Related to SGLT2 Inhibitors? An Online Survey Study.

Previous studies have found differences in the communication of safety issues among medicines regulatory agencies. To explore (1) to what extent regulators' opinions regarding the need to communicate safety issues related to sodium-glucose cotransporter-2 (SGLT2) inhibitors might be influenced by their concern about the safety issue, and (2) whether regulators' concerns might be influenced by certain characteristics of the safety issue or by the demographic and professional characteristics and attitudes of the regulators. An online cross-sectional survey study with a rating-based conjoint analysis among clinical and pharmacovigilance assessors from the EU regulatory network was performed between April and June 2021. Regulators were invited by email, and participants were asked about their level of concern and their opinion regarding the need to communicate about 12 scenarios defined by four characteristics: adverse drug reaction, source of information, causality, and frequency. The outcomes for the first objective were to update the summary of product characteristics (SmPC; yes/no) and to send direct healthcare professional communications (DHPC; yes/no). The determinant was regulators' level of concern (range 0-100%). The outcome of the second objective was regulators' level of concern, and the determinants were the characteristics of the safety issue, demographic and professional characteristics, and attitudesof the regulators (beliefs about medicines and risk perception). A total of 222 regulators completed the survey (64% women; mean age 46 ± 10 years). Depending on the scenario, 54-94% and 25-74% of the participants would update the SmPC or send a DHPC, respectively. The participants' level of concern influenced their opinions regarding the need to update the SmPC and send a DHPC (odds ratio (OR) 13.0; 95% confidence interval (CI) 7.8-21.7 and OR 13.6; 95% CI 9.5-19.2, respectively, for every 10% increase in the level of concern). All characteristics of the safety issue influenced the level of concern. Younger participants, women, and those working for Eastern European agencies had a higher level of concern than older participants, men, and those working in other regions. Beliefs about medicines and general risk perception also influenced their concern. The opinion regarding the need to communicate safety issues was influenced by the concern of regulators. Regulators' concern was influenced bythe characteristics of the safety issue, demographic characteristics, and attitudes. Diverse groups of experts regarding such factors would ensure that various views are incorporated in risk communication decisions.

The Awareness and Adherence of the Valproate Pregnancy Prevention Program: A Questionnaire Survey among Healthcare Professionals, Pharmacists, and Patients in Denmark.

The European Medicine Agency (EMA) provided additional recommendations regarding the use of valproate during pregnancy in 2018 by introducing a pregnancy prevention program (PPP). This study aimed to investigate the adherence and the impact of the PPP and the awareness of valproate teratogenicity among Danish healthcare professionals (HCPs) and patients. As part of the EMA initiated multi-country survey, web-based questionnaires were distributed among Danish general practitioners (GPs), medical specialists, pharmacists, and patients. A total of 90 prescribers, 98 pharmacists, and 103 patients were included in the study. Some 95.0% of the prescribers, 78.6% of the pharmacists, and 81.6% of the patients were aware of the teratogenic risks of valproate. The patient guide (27.8%), the HCP guide (23.3%), direct healthcare professional communication (23.3%), and the warning sign on the outer medication package (23.5%) were the most applied measures from the PPP. A total of 54.4% of the prescribers and 32.7% of the pharmacists informed patients about the importance of effective contraception during the use of valproate. The study showed that in Denmark HCPs and patients are highly aware of the teratogenic effects of valproate. However, adherence to and the impact of the measures included in the PPP were low.

Effect of the direct healthcare professional communication on citalopram and escitalopram drug utilization for inpatient treatment of anxiety disorders

In 2011, direct healthcare professional communication (DHPC) letters on citalopram and escitalopram were sent out to address the risk of QTc prolongation in the ECG. Healthcare professionals were informed about areduction of the maximum recommended daily dose. Furthermore, acontraindication for QTc-prolonging co-medication was given. Previous studies noted that these instructions were implemented incompletely. For the first time, this study analyzed how the DHPC affected the prescription of citalopram and escitalopram in patients with anxiety disorders. Drug utilization data from the project "Arzneimittelsicherheit in der Psychiatrie e. V." (AMSP) was used to examine whether the proportion of patients treated with ahigher-than-recommended daily dose ("high dose") and the proportion of patients with QTc-prolonging co-medication would decrease post-DHPC (combined category of citalopram/escitalopram). Drug utilization data of n = 364patients pre- and n = 262patients post-DHPC were compared. The proportion of patients with high dose declined from 10.7% to 5.4% (p = 0.019). The proportion of patients with QTc-prolonging co-medication did not change significantly from pre- (54.7%) to post-DHPC (51.5%, p = 0.437). In accordance with previous studies, the proportion of high-dose patients decreased after DHPC publication while the proportion of patients with QTc-prolonging co-medication remained widely unchanged. The specific recommendation on daily dosage seems to have been better implemented than the broadly formulated contraindication of QTc-prolonging co-medication. Hence, DHPCs should be written precisely and give advice for specific clinical situations.

Factors Influencing Preferences and Responses Towards Drug Safety Communications: A Conjoint Experiment Among Hospital-Based Healthcare Professionals in the Netherlands.

IntroductionHealthcare professionals (HCPs) are informed about new drug safety issues through Direct Healthcare Professional Communications (DHPCs). The influence of DHPC content on the impact of the communication is unclear.ObjectivesThe aim of this study was to assess the effect of content elements ‘frequency of the safety issue’, ‘seriousness of the safety issue’, ‘need to take action’, ‘life span of drug involved’ and ‘type of evidence supporting the safety issue’ on hospital-based HCPs’ preferences and responses towards DHPCs.MethodsA survey study including a conjoint experiment was performed among hospital-based HCPs in the Netherlands. Hypothetical DHPCs varying on the five content elements were constructed. Each respondent received eight out of 16 hypothetical DHPCs and was asked about (1) importance to be informed (fixed-point scale), (2) preferred communication timing (multiple options) and (3) their stated actions (multiple options). Associations were tested using generalized linear mixed models.ResultsIn total, 178 HCPs participated. DHPCs concerning more frequent or serious safety issues, or requiring action, were associated with a higher perceived importance to be informed and a preference for immediate communication. Periodic communication was preferred for DPHCs concerning less frequent or serious safety issues. The most commonly stated action was to discuss the DHPC with colleagues. Monitoring was common when this was recommended. High frequency and seriousness were associated with more prescribing-related actions.ConclusionFrequency and seriousness of the safety issue and the recommended action are likely to influence the impact of DHPCs. The timing of communication could be tailored depending on the content, where less urgent safety issues might be communicated periodically.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-022-01230-y.

Liver Transplantation for Metamizole induced Acute Liver Failure

Metamizole, or dipyrone, is a frequently prescribed analgetic drug that can cause drug-induced liver injury (DILI). Still, there are only a few metamizole-associated DILI cases (n=61, including our study) described in the literature. So far liver transplantation has been reported in 6 patients with metamizole-induced acute liver failure. In 2020, a German group described a bigger cohort (n=23) of metamizole-related DILI. Shortly thereafter, this issue gained wider attention as the German Federal Institute for Drugs and Medical Devices published a Direct Healthcare Professional Communication, emphasizing DILI as a potential adverse event caused by metamizole. We herein report 2 patients that were admitted to our liver transplant center due to acute liver failure (ALF) in April and May 2021. Both patients reported intake of metamizole as pain medication over a few weeks. After ruling out alternative reasons for ALF and fulfilling the King's College criteria both patients received emergency liver transplantations in our center. Pathology assessment of both explants were consistent with metamizole-associated DILI. As illustrated by our 2 cases of metamizole-induced liver failure with subsequent liver transplantation, this rare but presumably often overlooked adverse drug effect of metamizole should be considered as differential diagnosis in cases of cryptogenic liver failure.

Enhancing medication risk communication in developing countries: a cross-sectional survey among doctors and pharmacists in Malaysia

BackgroundMedication risk communication is essential to ensure the safe use of medicines. However, very few nations worldwide have established effective risk communication systems. To date, the effectiveness of risk communication among healthcare professionals in Malaysia has never been evaluated. Our study aimed to (i) evaluate doctors’ and pharmacists’ awareness of regulatory risk communication methods; (ii) identify factors predicting the usefulness of these methods; and (iii) compare respondents’ preferences for risk communication to outline suggestions for enhancement.MethodsWe conducted a nationwide cross-sectional survey covering four commonly used risk communications, namely a national drug bulletin, safety alerts, Direct Healthcare Professional Communication letters (DHPCs), and educational materials. Multiple logistic regression analysis was used to determine the association between independent variables and the usefulness of risk communication. We performed qualitative analysis of free-text responses to gain insights on respondents’ perspectives on risk communication.ResultsOf the 1146 responses received, 650 were from pharmacists (56.7%). Among the four methods surveyed, 71.5% of respondents were aware of educational materials, while awareness of the other three methods ranged from 20.7 to 53.9%. Pharmacists had higher awareness of all four methods compared to doctors. Private sector respondents were more aware of DHPCs compared to those from the public sector. The strongest predictors for finding risk communication useful were being a pharmacist [odds ratio (OR) = 18.2; 95% CI: 10.98–30.07; p < 0.001], having ≥30 years’ work experience [OR = 4.9; 95% CI: 1.98–12.08; p < 0.001], and working in the pharmaceutical industry [OR = 4.6; 95% CI: 1.08–19.72; p = 0.039]. Both doctors and pharmacists preferred risk communication in the English-language and electronic format. However, other preferences differed between the professions and sectors. Analysis of free-text comments revealed five core themes to guide risk communication enhancement strategies.ConclusionsRisk communication awareness differed between public and private sector doctors and pharmacists depending on communication source. Integrating our findings with the theory of effective communication, we provide suggestions for developing strategic plans on enhancing risk communication. Public-private sector collaboration is key in ensuring risk communication effectiveness.

Handling of New Drug Safety Information in the Dutch Hospital Setting: A Mixed Methods Approach.

IntroductionThe implementation of new drug safety information and Direct Healthcare Professional Communications (DHPCs) in hospitals is important for patient safety.ObjectivesThe aim of this study was to gain insight into which procedures and practices are in place to handle new drug safety information and particularly DHPCs in the Dutch hospital setting.MethodsWe first conducted focus groups including medical specialists and hospital pharmacists, focusing on handling of drug safety information at the individual and organisational level. A survey was then developed and distributed among hospital pharmacists in all Dutch hospitals to quantify the existence of specific procedures and committees to handle drug safety information and DHPCs.ResultsEleven specialists and 14 pharmacists from six hospitals participated in focus groups. Drug safety information was usually considered before drugs were included in formularies or treatment protocols. Furthermore, drug safety information was consulted in response to patients experiencing adverse events. DHPCs were mostly dealt with by individual professionals. DHPCs could lead to actions but this was very uncommon. Completed surveys were received from 40 (53%) of the hospitals. In 32 (80%), the hospital pharmacy had procedures to deal with new drug safety information, whereas in 11 (28%) a hospital-wide procedure was in place. Drug safety was considered in committees concerning drug formulary decisions (69%) and antibiotic policies (63%). DHPCs were assessed by a hospital pharmacist in 50% of the hospitals.ConclusionsDrug safety information was used for evaluation of new treatments and in response to adverse events. Assessment of whether a DHPC requires action was primarily an individual task.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-022-01149-4.

Dear Doctor Letters regarding citalopram and escitalopram: guidelines vs real-world data

Dear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs’ effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14–5% and 47–31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs’ recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.

Survery of healthcare professionals to assess the awareness, knowledge and self-reported behavior regarding recent fluoroquinolones safety issues.

The impact of fluoroquinolone (FQ)-induced long-lasting, disabling, and potentially irreversible serious adverse drug reactions (ADRs) on the overall benefit-risk balance and the need for adequate risk minimization measures has been recently assessed. The present study aims to evaluate physicians and pharmacists' awareness and knowledge of the recent safety issues communicated through a direct healthcare professional communication (DHPC), regarding FQs, at a national level, in Romania, as well as healthcare professionals (HPs) self-reported behavior regarding the management of the risk. Cross-sectional, online survey study, conducted in Romania. A total of 127 participants responded to the survey. Six (4.7%) were physicians and 121 (95.3%) were pharmacists. The predominant age was 31-40 years (N=52, 40.9%), and most respondents were females (N=117, 92.1%). A majority of 101 (79.5%) were reportedly aware of the existence of the new safety issues associated with FQs, and slightly less were aware of the DHPC (N=86, 67.7%) issued in 2019. In terms of knowledge, slightly more than half of the respondents had correctly selected the responses regarding key safety messages on most important ADRs and restrictions / cautions for use. The impact of the communication on HPs self-reported behavior was high or very high in almost half of the participants (N=63, 49.6%). A high percentage of participants were aware of the FQ-associated safety concerns. Knowledge was relatively good for the key safety concerns among HPs. A notable impact on behavior was observed, mostly in terms of counselling of the patient and disseminating the information to colleagues.

Near-death of Australia's Medicines Safety Update.

The Therapeutic Goods Administration has since 2013 neglected its long tradition of publishing regular bulletins and updates about medicine safety issues directed to Australian healthcare professionals. Recent publication policy is confused with information about clinically important safety issues published only in the alternative Safety Information Alerts and, unlike other comparable regulators, a failure to publish direct healthcare professional communications.

Direct healthcare professional communications: A quantitative assessment study.

A retrospective observational study evaluated the direct healthcare professional communication (DHPC) letters disseminated by the Saudi Food and Drug Authority (SFDA) and their compliance with the pharmacovigilance guidelines. The study was utilized all DHPC letters available on the SFDA website, which is intended to communicate drug safety information to healthcare professionals (HCPs). Then, the letters were evaluated based on DHPC letter requirements approved in the European Medicines Agency (EMA) pharmacovigilance guidelines. Statistical analyses were conducted utilizing statistical analysis software (SAS® version 9.4). In June 2020, 169 letters were retrieved from the SFDA website. Most of the letters had the marketing authorization holder's logo (97%) and mentioned the date of letter issuance (98.8%). The most frequently discussed safety issues were hyperkalemia risk associated with combining renin–angiotensin–aldosterone system (RAAS) medications (10.6%) and cardiac risks (9%). Antineoplastic and immunosuppressant classes were associated with a majority of DHPC letters (15% for each category). A significant percentage of DHPC letters (10%) did not mention an agreement statement with SFDA, and 42 letters did not include marketing authorization holders (MAHs) contact information. The qualified persons responsible for pharmacovigilance and medical directors had signed most of the DHPC letters (51% and 46%, respectively). Many letters mentioned the details of reporting information to both SFDA and an MAH (82%). Moreover, 66% of the DHPC letters presented safety information within the 2‐page limit. In conclusion, the DHPC letters disseminated by MAHs in Saudi Arabia have an acceptable level of compliance with the guidelines.

The European coalition for vaccination calls on healthcare professionals to get vaccinated against COVID-19

In February 2021, the Coalition for Vaccination has published a manifesto to encourage healthcare professionals to get vaccinated against COVID-19. The manifesto highlights three key reasons why all healthcare professionals...

Dissemination of Direct Healthcare Professional Communications on Medication Errors for Medicinal Products in the EU: An Explorative Study on Relevant Factors.

IntroductionWhen serious medication errors (ME) are identified, communication to the field may be necessary. In the EU, communication of serious safety issues, such as medication errors associated with adverse drug reactions, is done through direct healthcare professional communications (DHPCs). We aimed to identify how often DHPCs about medication errors are distributed, and we explored factors associated with these ME DHPCs.MethodsWe performed a descriptive study of all centrally authorised products (CAPs) approved before 1 May 2019 in the EU. All DHPCs issued between 1 January 2001 and 1 May 2019 were reviewed for ME content. Characteristics of CAPs were collected from the website of the European Medicines Agency. A Kaplan–Meier survival analysis was performed to estimate the 5- and 10-year probability of the occurrence of a first ME DHPC. A logistic regression was performed to explore risk factors for ME DHPCs.ResultsA total of 678 CAPs were included, of which 35 required an ME DHPC during the study period. The 5-year probability for a CAP to have a first ME DHPC was 2.5% (95% CI 1.1–3.9) and the 10-year probability was 4.4% (95% CI 2.2–6.5). Among products with an ME DHPC, the 5-year probability of a second ME DHPC was 21.3% (95% CI 0.2–38.0). The risk of ME DHPCs was increased for products with multiple pharmaceutical formulations, enteral liquid or parenteral injection preparations, and products classified as nervous system agents or antineoplastic and immunomodulating agents.ConclusionsThe absolute number of ME DHPCs for CAPs is low and does not give rise to immediate concern. We identified potential risk factors for ME DHPCs that should be taken into account during approval procedures or line extensions.Electronic supplementary materialThe online version of this article (10.1007/s40264-020-00995-4) contains supplementary material, which is available to authorized users.

Introduction or Discontinuation of Additional Risk Minimisation Measures During the Life Cycle of Medicines in Europe.

IntroductionAdditional risk minimisation measures (aRMMs) may be required to minimise important risks of medicines. aRMMs may be required at the time of authorisation, but may also be introduced or discontinued during the product life cycle as new safety information arises. The aim of this study is to describe post-authorisation introductions of new aRMMs and discontinuations of existing aRMMs for medicines authorised in the European Union (EU).MethodsWe performed a retrospective cohort study that included all new active substances authorised through the EU centralised procedure between January 1st 2006 and December 31st 2017. Data was extracted from European Public Assessment Reports available on the website of the European Medicines Agency (ema.europa.eu). Medicines were followed up from the date of marketing authorisation (MA) until first introduction or discontinuation of aRMMs, excluding Direct Healthcare Professional Communications (DHPCs), withdrawal/suspension/revocation of the MA, or July 1st 2018, when data extraction took place. Descriptive statistics were used to analyse frequency data, and survival analysis was used to calculate 5- and 10-year probability of introduction or discontinuation of aRMMs.ResultsA total of 476 medicines were authorised during the study period. The probability of getting aRMMs after authorisation for products authorised without aRMMs was 3.5% [95% confidence interval (CI) 1.2–5.7] within 5 years after authorisation and 6.9% (95% CI 2.6–11) within 10 years after authorisation. For products authorised with aRMMs, the probability of discontinuation of aRMMs was 0.9% (95% CI 0–2.6) within 5 years and 8.3% (95% CI 0–16.1) within 10 years after authorisation.ConclusionsWe found low probabilities of introduction and discontinuation of aRMMs (excluding DHPCs) during the product life cycle for medicines authorised between 2006 and 2017. The low rate of discontinuation may potentially be due to a lack of robust data on effectiveness of aRMMs. Further research is needed to get more insight into the dynamics of aRMMs during the medicine life cycle.

Are monitoring instructions provided in direct healthcare professional communications (DHPCs) of sufficient quality? A retrospective analysis of DHPCs sent out between 2007 and 2018

ObjectiveTo assess whether direct to healthcare professional communications (DHPCs) are of sufficient quality to be applicable in clinical practice and study how the quality differs according to safety concerns and...

Evaluating the Effectiveness of an Additional Risk Minimization Measure to Reduce the Risk of Prescribing Mirabegron to Patients with Severe Uncontrolled Hypertension in Four European Countries.

BackgroundMirabegron, indicated for the treatment of overactive bladder, is contraindicated in patients with severe uncontrolled hypertension (systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg). In September 2015, a Direct Healthcare Professional Communication (DHPC) letter was disseminated as an additional risk minimisation measure.PurposeTo assess the effectiveness of the DHPC in reducing the proportions of patients with severe or non-severe uncontrolled hypertension at mirabegron initiation.MethodsAn observational multi-database cohort study was undertaken using routinely collected healthcare data (December 2012–December 2016) from the PHARMO Database Network (Netherlands), SIDIAP database (Spain), CPRD (United Kingdom, UK) and national healthcare registers and electronic medical records from Finland. DHPC effectiveness was evaluated using interrupted time series analyses comparing trends and changes in monthly proportions of severe or non-severe uncontrolled hypertensive mirabegron initiations relative to the timing of the DHPC dissemination.ResultsThe study population comprised 52,078 patients. Prior to DHPC dissemination, across the four databases, 0.3–1.3% had severe uncontrolled hypertension. Estimated absolute changes (EAC) in proportions of severe uncontrolled hypertension post-DHPC indicated a tendency towards a lower proportion in the Netherlands (EAC −0.36%, p=0.053), unchanged proportions in Spain and the UK and a higher proportion in Finland (EAC +0.73%, p=0.016). For non-severe uncontrolled hypertension (13–16% pre-DHPC), post-DHPC proportions tended to be lower in the Netherlands (EAC −2.02%, p=0.038) and Spain (EAC −1.04%, p=0.071), and unchanged in the UK and Finland.ConclusionSevere uncontrolled hypertension prior to mirabegron initiation was uncommon in these four European countries even before DHPC dissemination. This suggests that other risk minimisation communications (prior to the DHPC dissemination) had worked adequately with respect to minimising mirabegron use among patients with severe uncontrolled hypertension. No strong and consistent evidence of further risk minimisation after the DHPC dissemination was observed in this study.

A description of medicines-related safety issues evaluated through a referral procedure at the EU level after 2012

ABSTRACT Introduction Important drug safety issues are evaluated through a referral procedure in the EU by the Pharmacovigilance Risk Assessment Committee (PRAC) within the European Medicines Agency. We aim to describe all safety-related referrals assessed by the PRAC by June 2019. Methods Publicly available data on safety issues assessed through referral procedures that reached a final decision during July 2012–June 2019 were identified, analyzed and classified according to predefined criteria. Results Fifty-one safety issues were assessed by PRAC for 45 medicines/combinations/therapeutic classes during this timeframe. Referrals were initiated mostly by the European Commission (16) and France (8). Nine medicines were authorized in the last five years, the rest being well-established drugs. In four cases (flupirtine, hydroxyethyl-starch, valproate, codeine) PRAC re-assessed the same risks as previous recommendations have not been effective. Post-referral recommendations consisted of updates of the summary of product characteristics and package leaflet (42), Direct Healthcare Professional Communication (32), and other additional risk minimization measures (RMMs). Withdrawal was recommended for seven active substances. Conclusions PRAC recommended routine or additional RMMs for most referrals. Complete withdrawal of a drug or withdrawal of certain pharmaceutical forms or concentrations was advised only when the risk could not be managed by RMMs.

Drug Safety Issues Covered by Lay Media: A Cohort Study of Direct Healthcare Provider Communications Sent between 2001 and 2015 in The Netherlands.

BackgroundSome drug safety issues communicated through direct healthcare professional communications (DHPCs) receive substantial media coverage, while others do not.ObjectivesThe objective of this study was to assess the extent of coverage of drug safety issues that have been communicated through DHPCs in newspapers and social media. A secondary aim was to explore which determinants may be associated with media coverage.MethodsNewspaper articles covering drug safety issues communicated through 387 DHPCs published between 2001 and 2015 were retrieved from LexisNexis Academic™. Social media postings were retrieved from Coosto™ for drugs included in 220 DHPCs published between 2010 and 2015. Coverage of DHPCs by newspapers and social media was assessed during the 2-month and 14-day time periods following issuance of the DHPC, respectively. Multivariate logistic regression was used to assess potential DHPC- and drug-related determinants of media coverage.Results41 (10.6%) DHPC safety issues were covered in newspaper articles. Newspaper coverage was associated with drugs without a specialist indication [adjusted odds ratio 5.32; 95% confidence interval (2.64–10.73)]. Negative associations were seen for time since market approval [3–5 years 0.30; (0.11–0.82), 6–11 years 0.18; (0.06–0.58)] and year of the DHPC [0.88; (0.81–0.96)]. In the social media, 180 (81.8%) drugs mentioned in 220 DHPCs were covered. Social media coverage was associated with drugs without a specialist indication [6.92; (1.56–30.64)], and for DHPCs communicating clinical safety issues [5.46; (2.03–14.66)].ConclusionsNewspapers covered a small proportion of DHPC safety issues only. Most drugs mentioned in DHPCs were covered in social media. Coverage in both media were higher for drugs without a specialist indication.Electronic supplementary materialThe online version of this article (10.1007/s40264-020-00922-7) contains supplementary material, which is available to authorized users.