Drug Benefit Research Articles

What constitutes meaningful benefit of cancer drugs in the context of LMICs? A mixed-methods study of oncologists’ perceptions on endpoints, benefit, price, and value of cancer drugs

What constitutes meaningful benefit of cancer drugs in the context of LMICs? A mixed-methods study of oncologists’ perceptions on endpoints, benefit, price, and value of cancer drugs

Prescription rebate guarantees: employerinsights.

To describe (1) rebate arrangements for specialty drugs, (2) the use and influence of benefits brokers and consultants, and (3) the importance of rebate-related factors when selecting a pharmacy benefits manager (PBM) among a sample of employers with self-funded pharmacybenefits. A national survey of employer drug benefit decision makers (N = 110) for organizations with self-insured pharmacy benefits. We summarized respondents' current rebate agreements for specialty drugs and their perspectives on the importance of rebates and rebate guarantees overall as well as by type of rebate agreement and by the person or entity identified as most influential in rebate strategy. Nearly two-thirds of employers reported having rebate agreements with a rebate guarantee for specialty drugs (n = 69; 62.7%). The person or entity most influential to rebate strategy decisions was often a benefits consultant (37.3%), a human resources/benefits leader (29.1%), or a benefits broker (21.8%). Employers with rebate guarantees ascribed a higher level of importance to guarantees when selecting a PBM (median [IQR], 9 [7-10]) than employers receiving rebates without a guarantee (7 [6-8]) and those who do not receive rebates (7.5 [4-9]) (P = .001). These findings shed light on the importance of rebate guarantees and the role of employer benefits consultants and brokers in PBM selection. Asthe public discourse on PBMs and drug rebates continues, it is important to recognize the role employer benefits consultants may play in perpetuating employer reliance on guaranteed rebate arrangements.

BRCA Mutation in Ovarian Cancer: Implications for Screening, Diagnosis, and Preventive Measures

Ovarian cancer is the most common gynaecological malignancy and the seventh most common malignancy in women. Inherited ovarian cancer is caused by mutations in certain genes, such as BRCA1 and BRCA2, as well as many minor genes. The pathology of ovarian cancer involves damage to the cell cycle mechanism secondary to mutations in BRCA1/2 protective genes. These mutations provide a meaningful marker for screening and diagnosing hereditary ovarian cancer. Classification of ovarian cancer is based on histology, depending on which layers of the ovary are affected. The authors conducted an electronic search using keywords and selected the included studies based on pre-established inclusion criteria. To avoid bias in the data extraction process, three reviewers extracted information independently. Risk assessment models provided by the National Comprehensive Cancer Network (NCCN) and American College of Obstetricians and Gynecologists (ACOG) are mostly used in clinical practice. The combination of serial serum cancer antigen-125 (CA-125) levels and transvaginal ultrasound is the only evidence-based screening approach available to patients at increased risk for ovarian cancer. Strong evidence has made salpingo-oophorectomy the gold standard for risk-reducing surgery. Bilateral salpingectomy, in contrast, is restricted to clinical trials currently. The protective effects of oral contraceptives have made them suitable agents for chemoprevention. Whilst the potential benefits of aspirin and certain other drugs have been investigated, further research is required to address the gap in data for them to be used in clinical practice for the purpose of ovarian cancer prevention.

Clinical Benefit, Price, and Regulatory Approval of Cancer Drugs Granted Breakthrough Therapy Designation in China, 2020-2024

The China National Drug Administration (NMPA) established the breakthrough therapy designation (BTD) in 2020 to encourage the accelerated development of drugs for the prevention and treatment of diseases that are life-threatening. However, the differences between BTD and non-BTD cancer drugs regarding clinical benefit, regulatory approval, and price are unclear. To compare BTD and non-BTD cancer drugs in clinical benefit (defined as efficacy and safety), novelty, time to approval, and average monthly treatment price. This cross-sectional study analyzes the original indication of BTD and non-BTD novel cancer drugs approved by the NMPA between July 8, 2020, and July 8, 2024. Data on efficacy, safety, regulatory approval, and price of cancer drugs were extracted from pivotal clinical trials based on review reports published by the NMPA, peer-reviewed articles or meeting reports, and winning bid prices for cancer drugs in the Chinese provincial-level centralized procurement process. The main outcome was the efficacy and safety associated with BTD vs non-BTD cancer drugs, including progression-free survival (PFS), response rate (RR), duration of response, serious adverse events, grade 3 or higher adverse events, and treatment-related deaths. In addition, the time to approval, novelty, and initial and latest average monthly treatment prices were evaluated, as well as the average annual reduction rate (AARR; the sum of the reduction rates divided by the number of years for the monthly treatment price) for these cancer drugs. Between July 2020 and July 2024, 18 BTD (36%) and 32 non-BTD (64%) cancer drugs were approved by the NMPA. The median (IQR) clinical development time for BTD drugs was significantly shorter than for non-BTD drugs (5.6 [95% CI, 4.3-7.3] vs 6.6 [95% CI, 6.0-8.5] years; P = .02). No significant differences were observed in PFS (HR, 0.44 [95% CI, 0.38-0.52] vs HR, 0.51 [95% CI, 0.40-0.65]; P = .20), PFS gained (median [IQR], 5.4 [3.9-7.0] vs 2.7 [2.6-5.9] months; P = .77), RR (58% [95% CI, 45%-74%] vs 59% [95% CI, 51%-69%]; P = .85), and duration of response (median [IQR], 18.0 [15.0-21.6] vs 11.1 [7.4-17.4] months; P = .09) between BTD and non-BTD drugs. The rates of serious adverse events (37% [95% CI, 26%-52%] vs 32% [95% CI, 27%-36%]; P = .45), adverse events grade 3 or higher (64% [95% CI, 53%-77%] vs 55% [95% CI, 45%-68%]; P = .31), and treatment-related deaths (2% [95% CI, 1%-4%] vs 1% [95% CI, 1%-2%]; P = .10) were similar between BTD and non-BTD drugs. BTD drugs are more likely to be first-in-class drugs (5 of 18 [28%] vs 1 of 32 [3%]; P = .02). Differences in the median (IQR) initial ($5665 [$3542-$9321] vs $3361 [$2604-$5474]; P = .06) and latest ($5665 [$1553-$9321] vs $2145 [$1318-$4276]; P = .18) average monthly treatment prices for BTD drugs and non-BTD drugs were not significant. The median (IQR) AARRs for BTD drugs and non-BTD drugs were 15.2% (0%-46.9%) and 19.8% (1.0%-42.9%), respectively. The findings of this cross-sectional study suggest that BTD has facilitated faster time to market for cancer drugs and improved novelty, but the price of treatment is relatively higher. There was no significant difference on comparative efficacy and safety.

Cosmeceuticals are the product of cosmetics that are biologically active ingredient that impersonates to medical or drug benefits. But the daily use of synthetic results in many side effects and need of organic lip balms is roaring in the society. In the

Cosmeceuticals are the product of cosmetics that are biologically active ingredient that impersonates to medical or drug benefits. But the daily use of synthetic results in many side effects and need of organic lip balms is roaring in the society. In the present study we, aimed to formulate organic lip balm using natural ingredients. Lip balm has been formulated using Golden shower flower, red cabbage, honey, ghee, beeswax, vitamin E and coconut oil. Various parameters such as stability, melting point, spreadability, pH, were evaluated for the evaluation of lip balm. pH was found to be 6 and melting point was 60°C 65°C for cassia lip balm and red cabbage lip balm respectively. On preforming skin irritation test the formulation was found to be not irritant, and formulation was observed to be stable. Lip balm from above ingredients could be a better option for daily use to a small extend for minor lip issues.

Early pirfenidone treatment enhances lung function in idiopathic pulmonary fibrosis patients.

This editorial comments on the study by Lei et al investigating the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis (IPF) published. This study evaluates the efficacy of early treatment with pirfenidone on lung function in patients with IPF. The early and advanced stages of IPF are defined, highlighting the drug's benefits. While prior research indicates pirfenidone's effectiveness in advanced IPF, this study focuses on its advantages in early stages. The study emphasizes the importance of computed tomography imaging alongside biochemical data and lung function tests for a comprehensive analysis of symptom relief. Results show that early intervention with pirfenidone significantly reduces disease progression and preserves lung function, underscoring its potential as a critical treatment strategy in early IPF.

The effects of sodium-glucose cotransporter 2 inhibitors on the 'forgotten' right ventricle.

With the progress in diagnosis, treatment and imaging techniques, there is a growing recognition that impaired right ventricular (RV) function profoundly affects the prognosis of patients with heart failure (HF), irrespective of their left ventricular ejection fraction (LVEF). In addition, right HF (RHF) is a common complication associated with various diseases, including congenital heart disease, myocardial infarction (MI), pulmonary arterial hypertension (PAH) and dilated cardiomyopathy (DCM), and it can manifest at any time after left ventricular assist devices (LVADs). The sodium-glucose cotransporter 2 (SGLT2) inhibition by gliflozins has emerged as a cornerstone medicine for managing type 2 diabetes mellitus (T2DM) and HF, with an increasing focus on its potential to enhance RV function. In this review, we aim to present an updated perspective on the pleiotropic effects of gliflozins on the right ventricle and offer insights into the underlying mechanisms. We can ascertain their advantageous impact on the right ventricle by discussing the evidence obtained in animal models and monumental clinical trials. In light of the pathophysiological changes in RHF, we attempt to elucidate crucial mechanisms regarding their beneficial effects, including alleviation of RV overload, reduction of hyperinsulinaemia and inflammatory responses, regulation of nutrient signalling pathways and cellular energy metabolism, inhibition of oxidative stress and myocardial fibrosis, and maintenance of ion balance. Finally, this drug class's potential application and benefits in various clinical settings are described, along with a prospective outlook on future clinical practice and research directions.

Digoxin Discontinuation in Patients with HFrEF on Beta-Blockers: Implication for Future “Knock-Out Trials” in Heart Failure

Background: National heart failure guidelines recommend quadruple therapy with renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors for patients with heart failure with reduced ejection fraction (HFrEF), most of whom also receive loop diuretics. However, the guidelines are less clear about the safe approaches to discontinuing older drugs whose decreasing or residual benefit is less well understood. The objective of this study was to examine whether digoxin can be safely discontinued in patients with HFrEF receiving beta-blockers. Methods: In OPTIMIZE-HF, of 2,477 patients with HFrEF (EF ≤45%) receiving beta-blockers and digoxin, digoxin was discontinued in 450 patients. We assembled a propensity score-matched cohort of 433 pairs of patients in which digoxin continuation vs. discontinuation groups were balanced on 51 baseline characteristics. Using the same approach, from 992 patients not on beta-blockers, we assembled a matched cohort of 198 pairs of patients also balanced on 51 baseline characteristics. Hazard ratios (HRs) and 95% CIs for one-year outcomes were estimated. Results: Among patients receiving beta-blockers, digoxin discontinuation had no association with the combined endpoint of heart failure readmission or death (HR, 1.01; 95% CI, 0.85–1.19), heart failure readmission (HR, 1.03; 95% CI, 0.85–1.25) or death (HR, 0.91; 95% CI, 0.72–1.14). Respective HRs (95% CIs) among patients not receiving beta-blockers were 1.60 (1.25–2.04), 1.62 (1.18–2.22) and 1.43 (1.08–1.89). Conclusions: Digoxin can be discontinued without increasing the risk of adverse outcomes in patients with HFrEF receiving beta-blockers. Future studies need to examine the residual benefit of older heart failure drugs to ensure their safe discontinuation in patients with HFrEF receiving newer guideline-directed medical therapy.

Protocolo terapéutico de la diabetes mellitus tipo 2 con obesidad y riesgo cardiovascular

The management of type 2 diabetes mellitus (DM2) with obesity and cardiovascular risk is a growing challenge due to the high prevalence of both conditions. This protocol describes therapeutic recommendations based on glycemic control and the cardiovascular benefits of certain drugs. Two classes of drugs with weight and cardiometabolic efficacy stand out: glucagon-like peptide-1 agonists (GLP-1a) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). This document suggests the joint use of both to reduce cardiovascular risk and promote weight loss. It also describes the role of metabolic surgery as an effective option for the management of DM2 and obesity, as it significantly improves glycemic outcomes and reduces cardiovascular risk. Continuous follow-up is recommended to adjust treatment according to the patient's clinical response and to avoid therapeutic inertia.

Disparities in the utilization of supportive care medications among older adults with metastatic pancreatic ductal adenocarcinoma.

51 Background: Inequities in cancer care delivery can profoundly affect access to high-quality treatments and patient outcomes. Supportive care medication use is important for preserving quality of life in older adults with metastatic pancreatic ductal adenocarcinoma (PDAC). Whether there are differences in supportive care medication use by race and sex is unknown. Our objectives were to assess the racial/ethnic and biological sex inequities in use of treatments for pain, depression, and pancreatic insufficiency-related treatments (PERT) among older adults with PDAC. Methods: We used the Surveillance, Epidemiology, and End Results-Medicare linked database, to identify Medicare beneficiaries aged 65 and older diagnosed with metastatic PDAC from January 2008 to December 2019. We included those continuously enrolled in Medicare prescription drug benefits in the 6 months before and month of diagnosis. Any use of opioid pain medications, antidepressants, and PERT was identified from diagnosis to the end of the study period (at death, disenrollment, or 12 months). Multivariable regression was used to compare supportive care medications use by racial/ethnic and biological sex groups. Results: There were 29,509 individuals in our sample, with12.9% Black patients, 3.9% Hispanic patients, and 83.2% White patients. The mean age was 76.5 (SD: 7.4) years. Mean follow-up time was 135.4 (SD:117.7) days overall, with the shortest follow-up among Black patients 124 (SD:111.1) days and longest for White patients 137.5 (SD: 118.8) days. Antidepressants were used by 23.8%, opioids by 60.3%, and PERT by 12.4% overall. Within race groups there were limited differences in medication use by sex. However, we observed differences in supportive care treatment use by race and ethnicity. Specifically, relative to White individuals, those who identified as Black were 20% less likely (adjusted risk ratio [aRR]: 0.8, 95% CI:0.74-0.85) to receive antidepressants, 14% less likely to receive opioids (aRR: 0.86, 95% CI:0.84-0.89), and 41% less likely to receive PERT (aRR: 0.59, 95% CI:0.53-0.65). Similar patterns were observed for patients of Hispanic ethnicity, with those individuals being 12% less likely (adjusted risk ratio[aRR]: 0.88, 95% CI:0.89-0.98) to receive antidepressants, 9% less likely to receive opioids (aRR: 0.91, 95% CI:0.87-0.96), and 42% less likely to receive PERT (aRR: 0.58, 95% CI:0.47-0.70). Conclusions: Our preliminary data showed differences in the uptake of supportive care drugs among Black and Hispanic patients relative to White patients. Specifically, these individuals were less likely to start opioid pain medications, antidepressants, and pancreatic enzyme replacement therapy compared to their White counterparts. These findings highlight potential gaps in treatment use that may better support patients facing life-limiting illnesses.

Experimental Study of the Promotional Implications of Proprietary Prescription Drug Names.

The meaning and characteristics embedded in proprietary drug names have the potential to affect name recall, perceptions of drug benefits and risks, and attitudes toward a drug. In this study, we examined: (1) whether names that reference the drug's medical indication affect consumers' and primary care physicians' (PCPs') perceptions of the drug and (2) whether names that overstate the drug's efficacy affect consumers' and PCPs' perceptions of the drug. We conducted an online experiment with 455 PCPs and 450 consumers to test the effects of fictitious proprietary prescription drug names. Participants were randomized to view one neutral drug name, one name that overstated the drug's efficacy, and five names that referenced the drug's medical indication. Names that referenced the drug's medical indication and names that overstated the drug's benefit both influenced perceptions of efficacy and risk compared to neutral names. For several outcomes, names evoking medical indications had similar effects to those designed to overstate the drug's efficacy. The patterns of effects were similar for PCPs and consumers. Findings suggest drug names alone can be sufficient to produce attitudes and risk and benefit perceptions about drugs, even in the absence of any information beyond the drug's medical indication.

Cyclic adenosine monophosphate critically modulates cardiac GLP-1 receptor's anti-inflammatory effects.

Glucagon-like peptide (GLP)-1 receptor (GLP1R) agonists exert a multitude of beneficial cardiovascular effects beyond control of blood glucose levels and obesity reduction. They also have anti-inflammatory actions through both central and peripheral mechanisms. GLP1R is a G protein-coupled receptor (GPCR), coupling to adenylyl cyclase (AC)-stimulatory Gs proteins to raise cyclic 3`-5`-adenosine monophosphate (cAMP) levels in cells. cAMP exerts various anti-apoptotic and anti-inflammatory effects via its effectors protein kinase A (PKA) and Exchange protein directly activated by cAMP (Epac). However, the precise role and importance of cAMP in mediating GLP1R`s anti-inflammatory actions, at least in the heart, remains to be determined. To this end, we tested the effects of the GLP1R agonist liraglutide on lipopolysaccharide (LPS)-induced acute inflammatory injury in H9c2 cardiac cells, either in the absence of cAMP production (AC inhibition) or upon enhancement of cAMP levels via phosphodiesterase (PDE)-4 inhibition with roflumilast. Liraglutide dose-dependently inhibited LPS-induced apoptosis and increased cAMP levels in H9c2 cells, with roflumilast but also PDE8 inhibition further enhancing cAMP production by liraglutide. GLP1R-stimulated cAMP markedly suppressed the LPS-dependent induction of pro-inflammatory tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6 cytokine expression, of inducible nitric oxide synthase (iNOS) expression and nuclear factor (NF)-kB activity, of matrix metalloproteinases (MMP)-2 and MMP-9 levels and activities, and of myocardial injury markers in H9c2 cardiac cells. The effects of liraglutide were mediated by the GLP1R since they were abolished by the GLP1R antagonist exendin(9-39). Importantly, AC inhibition completely abrogated liraglutide`s suppression of LPS-dependent inflammatory injury, whereas roflumilast significantly enhanced the protective effects of liraglutide against LPS-induced inflammation. Finally, PKA inhibition or Epac1/2 inhibition alone only partially blocked liraglutide`s suppression of LPS-induced inflammation in H9c2 cardiac cells, but, together, PKA and Epac1/2 inhibition fully prevented liraglutide from reducing LPS-dependent inflammation. cAMP, via activation of both PKA and Epac, is essential for GLP1R`s anti-inflammatory signaling in cardiac cells and that cAMP levels crucially regulate the anti-inflammatory efficacy of GLP1R agonists in the heart. Strategies that elevate cardiac cAMP levels, such as PDE4 inhibition, may potentiate the cardiovascular, including anti-inflammatory, benefits of GLP1R agonist drugs.

Summary of the 2023 European Society of Cardiology clinical guidelines on the management of cardiovascular disease in patients with diabetes mellitus

The prevalence of cardiovascular diseases (CVDs) is well known. According to the World Health Organization (WHO), almost 18 million people die from CVDs worldwide every year, accounting for 31% of all causes of death [1]. CVDs often develop concomitantly with diabetes mellitus (DM), with approximately 20% of cardiovascular deaths attributed to elevated blood glucose levels [2]. Notably, CVDs are the leading cause of death among patients with type 2 diabetes (T2DM). Based on data from the Federal Register of Diabetes 2022 in Russia, chronic heart failure was the direct cause of death in 24.2% of T2DM cases, followed by acute heart failure (13.1%), cerebrovascular events (10.0%), and myocardial infarction (3.7%) [3].The pathophysiological interplay between atherosclerotic cardiovascular disease and DM has led to a situation where cardiologists are increasingly involved in the treatment of patients with DM, while endocrinologists are encountering a growing number of patients with CVDs. This association has become so apparent that in a recent article published in the European Journal of Cardiology, Yu. Braunwald speculated about the emergence of a new subspecialty - diabetocardiology [4]. Unfortunately, experts predict that the global number of diabetic patients will reach 783 million [5].Recent data on the CV benefits of certain hypoglycemic drugs (primarily, certain SGLT2 inhibitors, several GLP-1 receptor agonists, and a novel non-steroidal mineralocorticoid receptor antagonist finerenone) prove the need for a unified interdisciplinary approach to managing CVDs and DM.Given the importance of integrated and coordinated efforts in managing patients with CVD and DM, the Task Force of the -European Society of Cardiology (ESC) updated, formulated, and published clinical guidelines on the treatment of CVD in diabetic patients in 2023 [6]. This article provides a concise overview of the key provisions outlined in the guidelines.

Evidence from an Applied Research Health Question (AHRQ): Physician-prescribed medications to children for oral health issues

ObjectivesTo understand changes in prescription patterns over time, and support dental and oral health program planning, Toronto Public Health issued an AHRQ request to collect information on physician-prescribed medications following an oral health-related incident. ApproachAn algorithm was created to identify oral health-related incidents among children and youth aged up to 17 years old in Ontario and Toronto during fiscal years 2013 to 2022. The algorithm used provincial data on physician visits, emergency department visits, inpatient hospitalizations, or day surgeries to define ‘dental-related incidents’. Physician-prescribed medications (e.g., chlorhexidine, opioids, benzodiazepines, antibiotics, NSAIDs and others) within seven days of a dental-related incident were recorded using Ontario Drug Benefit Claims and the Narcotics Monitoring System. ResultsOf 522,674 dental-related incidents in Ontario between 1 April 2013 and 31 March 2023, 9.2% had physician-prescribed medications (versus 8.6% of 90,810 dental-related incidents in Toronto). The proportion of incidents with prescriptions increased from 6.4% in 2013 to 10.7% in 2022 in Ontario, and from 5.9% to 10.3% in Toronto. The most prescribed medication was antibiotics, followed by immediate-release combination medications and non-long-acting medications. Conclusions/ImplicationsOver the 10-year period examined, an increasing proportion of dental-related incidents had physician-prescribed medications, which may be attributed to the implementation of Ontario’s pharmacare program (OHIP+) in 2018. Early access to routine and preventative dental care could become more accessible as part of Canada’s new federal dental program. Results from this AHRQ will inform better resource allocation in dental and oral health program planning, potentially reducing avoidable healthcare costs.

Treatment Effects in Randomized and Nonrandomized Studies of Pharmacological Interventions

Randomized clinical trials (RCTs) are widely regarded as the methodological benchmark for assessing clinical efficacy and safety of health interventions. There is growing interest in using nonrandomized studies to assess efficacy and safety of new drugs. To determine how treatment effects for the same drug compare when evaluated in nonrandomized vs randomized studies. Meta-analyses published between 2009 and 2018 were identified in MEDLINE via PubMed and the Cochrane Database of Systematic Reviews. Data analysis was conducted from October 2019 to July 2024. Meta-analyses of pharmacological interventions were eligible for inclusion if both randomized and nonrandomized studies contributed to a single meta-analytic estimate. For this meta-analysis using a meta-epidemiological framework, separate summary effect size estimates were calculated for nonrandomized and randomized studies within each meta-analysis using a random-effects model and then these estimates were compared. The reporting of this study followed the Guidelines for Reporting Meta-Epidemiological Methodology Research and relevant portions of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. The primary outcome was discrepancies in treatment effects obtained from nonrandomized and randomized studies, as measured by the proportion of meta-analyses where the 2 study types disagreed about the direction or magnitude of effect, disagreed beyond chance about the effect size estimate, and the summary ratio of odds ratios (ROR) obtained from nonrandomized vs randomized studies combined across all meta-analyses. A total of 346 meta-analyses with 2746 studies were included. Statistical conclusions about drug benefits and harms were different for 130 of 346 meta-analyses (37.6%) when focusing solely on either nonrandomized or randomized studies. Disagreements were beyond chance for 54 meta-analyses (15.6%). Across all meta-analyses, there was no strong evidence of consistent differences in treatment effects obtained from nonrandomized vs randomized studies (summary ROR, 0.95; 95% credible interval [CrI], 0.89-1.02). Compared with experimental nonrandomized studies, randomized studies produced on average a 19% smaller treatment effect (ROR, 0.81; 95% CrI, 0.68-0.97). There was increased heterogeneity in effect size estimates obtained from nonrandomized compared with randomized studies. In this meta-analysis of treatment effects of pharmacological interventions obtained from randomized and nonrandomized studies, there was no overall difference in effect size estimates between study types on average, but nonrandomized studies both overestimated and underestimated treatment effects observed in randomized studies and introduced additional uncertainty. These findings suggest that relying on nonrandomized studies as substitutes for RCTs may introduce additional uncertainty about the therapeutic effects of new drugs.

Physicians’ opinions on the utilization of generic medications in Gulf Cooperation Council countries: a narrative review

Abstract Objective This review paper explores strategies and recommendations for reducing healthcare expenses in the Gulf Cooperation Council (GCC) by understanding physicians’ attitudes regarding the utilization of generic medicines. Methods A comprehensive search of seven databases yielded 24 437 titles and abstracts. Using inclusion criteria focusing on physicians’ insights into generic prescribing and exclusion criteria, cutting out systematic reviews, case studies, and non-English articles, the review process led to an in-depth analysis of six studies. Results Findings revealed that while physicians generally comprehend terms like “generic”, “brand”, and “bioequivalence”, they face difficulty discussing bioequivalence with patients. Lack of emphasis on generic medicines in medical education and complex patient communication were potential impediments to generic medicine prescribing in the GCC countries. Strategies & Recommendations: Promoting the benefits of generic drugs could support their usage and help decrease healthcare costs. Improving medical education to include a larger focus on generic medications and their benefits, as well as training physicians in effectively communicating bioequivalence concepts to patients, could promote the use of more cost-effective, generic options. Conclusion The review calls for attention to the potential of generic medicine prescribing to reduce healthcare expenses in the GCC. Future research studies should consider broadening the geographical scope to provide global insights into these issues and their possible solutions.

Efficacy of β-Blockers in Decreasing Mortality in Sepsis and Septic Shock Patients: A Systematic Review.

Sepsis is a life-threatening condition leading to various organ dysfunction due to an underlying infection. Despite providing appropriate treatment, it is still one of the most common causes of death among patients who are admitted to the intensive care unit (ICU). So, multiple studies have been conducted to identify the potential benefits of various drugs in decreasing mortality in sepsis apart from its traditional treatment options. This study aims to identify whether β-blockers play a role in decreasing mortality in sepsis and septic shock patients because of their potential benefits on several organ systems. Medical databases such as Google Scholar, Summon, PubMed Medical Subject Headings (MeSH), PubMed, Science Direct, Cochrane Library, and Multidisciplinary Digital Publishing Institute (MDPI) were systematically searched for relevant publications. The identified articles were assessed based on the inclusion and exclusion criteria, and 11 research articles were finalized, for which quality appraisal was done using appropriate appraisal tools. β-blockers significantly lowered the in-hospital mortality in sepsis and septic shock patients, and they were also associated with better patient outcomes. As there are limited studies, further research needs to be done to explore the role of β-blockers in decreasing mortality in critically ill populations such as sepsis and septic shock patients.

The Association of Adverse Pregnancy Outcomes With Overactive Bladder Anticholinergics.

The pregnancy safety and teratogenicity of overactive bladder (OAB) anticholinergic medications in humans are unknown. The aim of this study was to determine if the use of OAB anticholinergics during pregnancy was associated with adverse pregnancy outcomes or congenital malformation. Using routinely collected health care data from Ontario, Canada, we conducted a retrospective cohort study and identified women aged 18-45 years who gave birth between 2004 and 2022 and were eligible for provincial drug benefits. We used gestational age and birth dates to approximate conception dates. The primary exposure was filling a prescription for an OAB anticholinergic during pregnancy (compared with nonusers). The coprimary outcomes were pregnancy complication (which included preterm birth or low birth weight) and congenital malformation. Poisson regression models with generalized estimating equations and inverse probability of treatment weighting were used to estimate risk ratios (RRs). We identified 138,271 births, of which 479 (0.3%) had exposure to an OAB anticholinergic, for a median of 60 (interquartile range, 30-120) days. The most common OAB anticholinergic was oxybutynin (84%). In the weighted cohort, the risk of a pregnancy complication was significantly elevated (RR, 1.65; 95% confidence interval [CI], 1.40-1.95; P < 0.01; absolute risk difference + 9.9% [95% CI, +5.9, +13.9]), with a dose-response relationship close to statistical significance (P = 0.07). The risk of congenital malformations with OAB anticholinergic use was not significant (RR, 1.24; 95% CI, 0.85-1.80; P = 0.26). Pregnant women who take OAB anticholinergic medications have a higher risk of pregnancy complications, but not congenital malformations, compared with non-OAB anticholinergic users. This information can be used when counseling women of child-bearing age about these medications.

Longitudinal cohort study highlights cancer-preventive benefits of lipid-lowering drugs

Cancer prevention is a serious global challenge. We aimed to investigate the relationship between lipid-lowering drugs and cancers. We included participants based on the UK Biobank. Lipid-lowering drug use was defined as new users before enrollment and the primary outcome was cancer incidence. The Cox proportional hazards regression model was used to evaluate the association between drug use and outcome. We also performed a meta-analysis. We found that lipid-lowering drugs were associated with decreased risk of 21 types of cancers, including melanoma, skin cancer, and reproductive, hematological, urinary, digestive, nervous, and endocrine system cancers (all p<0.0010). Our meta-analysis documented that lipid-lowering drugs reduced the risk of prostate, liver, and gastric cancers, especially (all p<0.050). Overall, lipid-lowering drugs had protective associations with cancer incidence, suggesting the possible cancer prevention effects even in the general population.

Clinical benefit, reimbursement outcomes, and prices of FDA-approved cancer drugs reviewed through Project Orbis in the USA, Canada, England, and Scotland: a retrospective, comparative analysis

Project Orbis is a global initiative that aims to streamline regulatory review processes across international regulators in the USA, Canada, Australia, UK, Israel, Brazil, Singapore, and Switzerland to bring promising cancer drugs to patients earlier. We explored the clinical benefit, time to regulatory approval and health technology assessment recommendations, reimbursement outcomes, and monthly treatment prices of cancer drugs reviewed through this initiative. For this retrospective, comparative analysis, we identified cancer drug approvals reviewed through Project Orbis in the USA, Canada, and the UK between May 1, 2019, and Nov 1, 2023. Approvals of cancer drugs reviewed Project Orbis were extracted from the Food and Drug Administration (FDA) Oncology Centre of Excellence and all other FDA approvals from the Drugs@FDA database. The co-primary outcomes were time of regulatory review, time from regulatory approval to health technology assessment recommendation (England, Scotland, and Canada), reimbursement outcomes, clinical benefit (defined as median gains in progression-free survival and overall survival) between cancer drug approvals reviewed by Project Orbis and other FDA approval processes, and monthly treatment prices. The Wilcoxon rank-sum and Fisher's Exact tests were used to examine statistical significance between approvals reviewed through Project Orbis and other FDA approvals during the same period. Between May 1, 2019 and Nov 1, 2023, 81 (33%) of 244 cancer drugs approved by the FDA were reviewed through Project Orbis. The median overall survival gains were 4·1 months (IQR 3·3-5·1) compared with 2·7 months (2·1-3·9) for other FDA approvals. Similarly, progression-free survival gains were 2·6 months (IQR 1·7-4·9) for Project Orbis compared with 2·6 months (0·6-5·1) for other FDA approvals. Neither overall survival (p=0·11) nor progression-free survival (p=0·44) gains were significantly different between the two cohorts of approvals. Of the 14 UK Medicines and Healthcare products Regulatory Agency (MHRA) approvals reviewed by the Scottish Medicines Consortium (SMC), the agency gave positive recommendations for all 14 (100%). Of the 15 MHRA approvals reviewed by the National Institute for Health and Care Excellence (NICE), the agency gave positive recommendations for six (40%). Of the 49 approvals reviewed by the Canadian Agency for Drugs and Technologies in Health (CADTH), the agency conditionally recommended 44 (90%). The time between regulatory approval to NICE recommendation increased from a median of 137 days (IQR 102-172) in 2021 to 302 days (184-483) in 2023, SMC recommendation increased from 185 days (in 2021 for one drug only) to 368 days (IQR 313-476) in 2023, and CADTH decision increased from 97 days (in 2020 for one drug only) to 202 days (IQR 153-304) in 2023. The median monthly price of approvals reviewed through Project Orbis was US$20 000 per month (IQR 13 000-37 000). Clinical outcomes of Project Orbis were no different than other FDA approvals during the same time, and access, after a successful health technology assessment, was considerably delayed or absent, raising questions about whether Project Orbis participation translates into faster patient access to medicines with high clinical benefit and sustainable costs. Although future challenges might benefit from regulatory harmonisation, the advantages are currently unclear. None.