Impact of Incorporating Future Mandatory Price Reductions with Generic Drug Entry on the Cost-Effectiveness of New Drugs: A Policy Simulation Study of Dupilumab in Atopic Dermatitis Treatment.

The introduction of high-cost medications often poses challenges in achieving cost-effectiveness for drug insurance coverage. Incorporating future price reductions for these medications may enhance their cost-effectiveness. We examined the influence of future cost reductions mandated by the national insurer's equal pricing for equivalent drugs (EPED) policy on the cost-effectiveness of dupilumab, a biologic drug for moderate to severe atopic dermatitis in the Korean healthcare system. We conducted a policy simulation study using semi-Markovian cost utility analysis of dupilumab in combination with supportive care (SC) versus SC alone, with and without the EPED policy adjustment. The EPED would lower dupilumab's price to 70% following the entry of a biosimilar drug in 10.3 years. Scenario analyses quantified the impact of changing time to the EPED, chemical versus biological designation, response criteria, discount rates, and time horizons on the Incremental Cost-Effectiveness Ratio (ICER) and acceptability with and without EPED adjustment. The EPED adjustment of dupilumab's future price significantly improved its cost-effectiveness, with a 9.7% decrease in ICER and a substantial 14.6% increase in acceptability. Assuming EPED in 5 years, the ICER fell below the predefined willingness-to-pay threshold. If dupilumab were a chemical drug, EPED adjustment demonstrated a 19.1% increase in acceptability. Incorporating future cost reductions via the EPED system in economic evaluations is crucial, especially for drugs facing imminent generic entry. This study underscores the importance of EPED adjustment in the cost-effectiveness analysis of innovative medications, especially for those nearing willingness-to-pay thresholds.

Identification of Emotional Spectrums of Patients Taking an Erectile Dysfunction Medication: Ontology-Based Emotion Analysis of Patient Medication Reviews on Social Media.

BACKGROUND: Patient medication reviews on social networking sites provide valuable insights into the experiences and sentiments of individuals taking specific medications. Understanding the emotional spectrum expressed by patients can shed light on their overall satisfaction with medication treatment. This study aims to explore the emotions expressed by patients taking phosphodiesterase type 5 (PDE5) inhibitors and their impact on sentiment. OBJECTIVE: This study aimed to (1) identify the distribution of 6 Parrot emotions in patient medication reviews across different patient characteristics and PDE5 inhibitors, (2) determine the relative impact of each emotion on the overall sentiment derived from the language expressed in each patient medication review while controlling for different patient characteristics and PDE5 inhibitors, and (3) assess the predictive power of the overall sentiment in explaining patient satisfaction with medication treatment. METHODS: A data set of patient medication reviews for sildenafil, vardenafil, and tadalafil was collected from 3 popular social networking sites such as WebMD, Ask-a-Patient, and Drugs.com. The Parrot emotion model, which categorizes emotions into 6 primary classes (surprise, anger, love, joy, sadness, and fear), was used to analyze the emotional content of the reviews. Logistic regression and sentiment analysis techniques were used to examine the distribution of emotions across different patient characteristics and PDE5 inhibitors and to quantify their contribution to sentiment. RESULTS: The analysis included 3070 patient medication reviews. The most prevalent emotions expressed were joy and sadness, with joy being the most prevalent among positive emotions and sadness being the most prevalent among negative emotions. Emotion distributions varied across patient characteristics and PDE5 inhibitors. Regression analysis revealed that joy had the strongest positive impact on sentiment, while sadness had the most negative impact. The sentiment score derived from patient reviews significantly predicted patient satisfaction with medication treatment, explaining 19% of the variance (increase in R2) when controlling for patient characteristics and PDE5 inhibitors. CONCLUSIONS: This study provides valuable insights into the emotional experiences of patients taking PDE5 inhibitors. The findings highlight the importance of emotions in shaping patient sentiment and satisfaction with medication treatment. Understanding these emotional dynamics can aid health care providers in better addressing patient needs and improving overall patient care.

Enhancing antidepressant safety surveillance: comparative analysis of adverse drug reaction signals in spontaneous reporting and healthcare claims databases.

Background/Objective: Spontaneous reporting systems (SRS) such as the Korea Adverse Event Reporting System (KAERS) are limited in their ability to detect adverse drug reaction (ADR) signals due to their limited data on drug use. Conversely, the national health insurance claim (NHIC) data include drug use information for all qualifying residents. This study aimed to compare ADR signal profiles for antidepressants between KAERS and NHIC, evaluating the extent to which detected signals belong to common ADRs and labeling information. Materials and Methods: ADR signal detection in KAERS and NHIC databases, spanning January to December 2017, employed disproportionality analysis. Signal classes were determined based on System Organ Class (SOC) of the Medical Dictionary for Regulatory Activities (MedDRA). Also, Common ADR Coverage (CAC), the proportion of detected signals deemed common ADRs, and labeling information coverage (LIC) represented by mean average precision (mAP) were calculated. Additionally, protopathic bias and relative risk (RR) evaluation were performed to check for signal robustness. Results: Signal detection revealed 51 and 62 signals in KAERS and NHIC databases, respectively. Both systems predominantly captured signals related to nervous system disorders, comprising 33.3% (N = 17) in KAERS and 50.8% (N = 31) in NHIC. Regarding the type of antidepressants, KAERS predominantly reported signals associated with tricyclic antidepressants (TCAs) (N = 21, 41.2%), while NHIC produced most signals linked to selective serotonin reuptake inhibitors (SSRIs) (N = 22, 35.5%). KAERS exhibited higher CAC (68.63% vs. 29.03%) than NHIC. LIC was also higher in KAERS than in NHIC (mAP for EB05: 1.00 vs. 0.983); i.e., NHIC identified 5 signals not documented in drug labeling information, while KAERS found none. Among the unlabeled signals, one (Duloxetine-Myelopathy) was from protopathic bias, and two (duloxetine-myelopathy and tianeptine-osteomalacia) were statistically significant in RR. Conclusion: NHIC exhibited greater capability in detecting ADR signals associated with antidepressant use, encompassing unlabeled ADR signals, compared to KAERS. NHIC also demonstrated greater potential for identifying less common ADRs. Further investigation is needed for signals detected exclusively in NHIC but not covered by labeling information. This study underscores the value of integrating different sources of data, offering substantial regulatory insights and enriching the scope of pharmacovigilance.

Comparison of the Erectile Dysfunction Drugs Sildenafil and Tadalafil Using Patient Medication Reviews: Topic Modeling Study.

BACKGROUND: Topic modeling of patient medication reviews of erectile dysfunction (ED) drugs can help identify patient preferences regarding ED treatment options. The identification of a set of topics important to the patient from social network service drug reviews would inform the design of patient-centered medication counseling. OBJECTIVE: This study aimed to (1) identify the distinctive topics from patient medication reviews unique to tadalafil versus sildenafil; (2) determine if the primary topics are distributed differently for each drug and for each patient characteristic (age and time on ED drug therapy); and (3) test if the primary topics affect satisfaction with ED drug therapy controlling for patient characteristics. METHODS: Data were collected from the patient medication reviews of sildenafil and tadalafil posted on WebMD and Ask a Patient. The latent Dirichlet allocation method of natural language processing was used to identify 5 distinctive topics from the patient medication reviews on each drug. Analysis of variance and a 2-sample t test were conducted to compare the topic distribution and assess whether patient satisfaction varies with the primary topics, age, and time on medication for each ED drug. Statistical significance was tested at an alpha of .05. RESULTS: The patient medication reviews of sildenafil (N=463) had 2 topics on treatment benefit and 1 each on medication safety, marketing claim, and treatment comparison, while the patient medication reviews of tadalafil (N=919) had 2 topics on medication safety and 1 each on the remaining subjects. Sildenafil's reviewers quite frequently (94/463, 20.4%) mentioned erection sustainability as their primary topic, whereas tadalafil's reviewers were more concerned about severe medication safety. Those who mentioned erection sustainability as their primary topic were quite satisfied with their treatment as opposed to those who mentioned severe medication safety as their primary topic (score 3.85 vs 2.44). The discovered topics reflected the marketing claims of blue magic and amber romance for sildenafil and tadalafil, respectively. The topic of blue magic was preferred among younger patients, while the topic of amber romance was preferred among older patients. The topic alternative choices, which appeared for both the ED drugs, reflected patient interest in the comparative effectiveness and price outside the drug labeling information. CONCLUSIONS: The patient medication reviews of ED drugs reflect patient preferences regarding drug labeling information, marketing claims, and alternative treatment choices. The patient preferences concerning ED treatment attributes inform the design of patient-centered communication for improved ED drug therapy.

The mediatory role of medication adherence in improving patients' medication experience through patient-physician communication among older hypertensive patients.

BACKGROUND: Understanding how patient-physician communication affects patients' medication experience would help hypertensive patients maintain their regular long-term medication therapy. This study aimed to examine whether patient-physician communication (information and interpersonal treatment) affects patients' medication experience directly or indirectly through changing medication adherence for each of the two communication domains. METHODS: A self-administered cross-sectional survey was conducted for older patients who had visited a community senior center as a member. Two communication domains were assessed using two subscales of the Primary Care Assessment Survey. Medication adherence and experience were measured using the Morisky Medication Adherence Scale and a five-point Likert scale, respectively. Mediatory effects were assessed via Baron and Kenny's procedure and a Sobel test. RESULTS: Patient-physician communication had a positive prediction on patients' medication experience (ß=0.25, P=0.03), and this was fully mediated by medication adherence (z=3.62, P<0.001). Of the two components of patient-physician communication, only informative communication showed a mediatory effect (z=2.21, P=0.03). CONCLUSION: Patient-physician communication, specifically informative communication, had the potential to improve patients' medication experience via changes in medication adherence. This finding can inform health care stakeholders of the mediatory role of medication adherence in ensuring favorable medication experience for older hypertensive patients by fostering informative patient-physician communication.

Natural killer T cell sensitization during neonatal respiratory syncytial virus infection induces eosinophilic lung disease in re-infected adult mice.

Respiratory syncytial virus (RSV) is a major viral pathogen that causes severe lower respiratory tract infections in infants and the elderly worldwide. Infants with severe RSV bronchiolitis tend to experience more wheezing and asthma in later childhood. Because invariant natural killer T (iNKT) cells are associated with the asthma pathology, we investigated whether neonatal iNKT cells are involved in the aggravation of pulmonary diseases following RSV infection in mice. Intranasal exposure to the iNKT cell ligand α-galactosylceramide (α-GC) with RSV primary infection in neonatal mice elicited neither cytokine production (except for a slight increase of IL-5) nor pulmonary eosinophilia, despite the presence of both CD1d+ cells and NKT cells. Interestingly, in adult mice re-infected with RSV, neonatal iNKT cell sensitization by α-GC during RSV primary infection resulted in much higher levels of pulmonary Th2 cytokines and elevated eosinophilia with airway hyperresponsiveness, whereas this was not observed in cd1d knockout mice. In contrast, α-GC priming of adults during RSV re-infection did not induce more severe airway symptoms than RSV re-infection in the absence of α-GC. α-GC co-administration during RSV primary infection facilitated RSV clearance regardless of age, but viral clearance following re-infection was not iNKT cell-dependent. This study clearly demonstrates that RSV-induced immune responses can be altered by iNKT cells, suggesting that neonatal iNKT cell sensitization during RSV primary infection is associated with exacerbation of pulmonary diseases following RSV re-infection in adulthood.

Neonatal immunization with respiratory syncytial virus glycoprotein fragment induces protective immunity in the presence of maternal antibodies in mice.

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly worldwide. The significant morbidity and mortality associated with this infection underscores the urgent need for development of RSV vaccine. In this study, we first show that intranasal administration of RSV glycoprotein core fragment (Gcf) to neonatal mice can induce systemic humoral immune responses and protective immunity against RSV without causing lung eosinophilia, although antibody response was shifted to a Th2 response. Next, we examined whether the presence of maternal anti-RSV antibodies would affect the responsiveness and protection efficacy of Gcf in newborn mice, since infants can possess RSV-specific maternal antibodies due to frequent RSV re-infections to adults. Intranasal administration of Gcf induced antibody response and increased IFNγ secretion and protected mice against RSV challenge without severe lung eosinophilia, even in the presence of high levels of RSV-specific maternal antibodies. Thus, our findings suggest that Gcf may be an effective and safe RSV vaccine during the neonatal period.