Charles River Associates

Background Declining fertility rates are a globally documented problem, affecting even regions that have historically high fertility rates. In the Asia Pacific (APAC) region, most countries and territories are seeing birth rates drop far below the replacement rate of 2.1 children per woman. Policymakers in these countries have switched from a historic focus on population control policies to investing in pronatalist policies that aim to boost the national fertility rate by tackling the socioeconomic drivers of falling fertility. In this paper, we examine policies affecting the often-overlooked medical aspect of this challenge: infertility. Objective To review challenges in fertility policy and propose solutions to improve equitable access to assisted reproductive technologies (ART) and associated services. Methods A review of literature was conducted on fertility policy challenges and developments in the APAC region, covering fertility recognition and awareness; egg freezing; and access to ART treatment, psychosocial care, and supplementary care. Experts from nine different countries and territories were invited to validate secondary research findings and provide their perspectives on policy implications. The experts participated in individual 60-minute interviews, then a half-day Policy Forum discussion was held at the Asia-Pacific Assisted Conception Congress 2024, held in Kuala Lumpur, Malaysia. Results Whilst several countries in the region have long recognised falling total fertility rates (TFR) as a cause for concern, many have been slow to recognise infertility as a disease, resulting in limited policy development to support patients experiencing infertility. Commonly this presents as lack of funding allocated towards fertility services, limited or no reimbursement of fertility treatment or egg freezing, and poor societal awareness of infertility and hence delays in seeking care. Various policy changes can be adopted to improve care for patients across the APAC region. Conclusion Our review identified multiple gaps in policy development for supporting individuals experiencing infertility. Looking to countries in which the TFR dropped below replacement level many years ago, the importance of timely policy intervention before negative demographic consequences occur is critical.

Purpose: Cardiovascular disease (CVD) is the leading cause of death among patients with prostate cancer (PC). Androgen deprivation therapy (ADT) remains the standard of care for advanced PC. Since 2010, the U.S. FDA has required warning labels for gonadotropin-releasing hormone agonists about increased risk for diabetes and some CVDs. This observational, retrospective, real-world study evaluated the risks of a first cardiovascular event within 3 years after initiation of ADT in patients with PC, with or without the presence of ≥ 1 of 3 cardiometabolic comorbidities: diabetes mellitus (DM), hypertension, and hyperlipidemia. Materials and Methods: Retrospective data (2010-2019) from a large administrative U.S. claims data set were analyzed to examine risk of first cardiovascular event based on the presence/absence of target comorbidities, alone or combined, using Cox regression modeling. Results: Of 10,530 patients with PC receiving ADT, 934 (8.9%) experienced a postindex cardiovascular event. Compared with patients without any of the 3 comorbidities, risk of cardiovascular events was greatest for patients with all 3 comorbidities (hazard ratio [HR], 95% confidence interval [CI], 2.15 [1.73-2.68]; P < .0001), followed by those with DM alone (HR [95% CI], 1.72 [1.28-2.31]; P = .0003). Having DM + hypertension or hypertension + hyperlipidemia also increased risk of a cardiovascular event. Conclusions: Patients with PC and comorbid DM, hypertension, and hyperlipidemia treated with ADT are at increased risk of a cardiovascular event after ADT initiation compared with patients without these comorbidities. This study provides a straightforward method to evaluate men with PC before starting ADT to identify patients at greatest risk for experiencing a cardiovascular event.

BackgroundLong-acting cabotegravir and rilpivirine (LA CAB/RPV) was approved in 2021 for treatment of HIV-1 to replace current antiretroviral therapy (ART) in those who are virologically suppressed with a viral load (VL) < 50 copies/mL. Challenges with patient access led to development of a standardized office-based LA CAB/RPV program in a network of Infectious Disease offices in the US. We reported initial success and patient adherence in 2024, and this study evaluates the long-term effectiveness of the LA CAB/RPV program.Table 1.Baseline Demographics and Treatment CharacteristicsFigure 1.Virologic Outcomes at Baseline and Follow-UpMethodsThe LA CAB/RPV program was initiated in July 2023 and the first 100 patients were followed through April 2025. Data collection included demographics, prior therapy, baseline and follow-up VL, adherence to schedule, adverse events, and reasons for discontinuation. Adherence was defined as LA CAB/RPV received within 7 days of target date.Table 2.Reasons for discontinuationResults100 pts from 20 sites were included. Patient and treatment characteristics are in Table 1. Median age was 49 years (IQR 39-59) with 81% male. Median BMI was 29.2 kg/m2 (IQR 27.1-31.9), with 38% ≥30 kg/m2. The majority (98%) received 2-month injections. The duration of therapy with LA CAB/RPV was 13 months (median, IQR 11-15), with 753 injections administered to date. Injections were administered on schedule in 94.8% of all doses. Virologic outcomes are noted in Figure 1. The baseline VL was 29 c/mL (median, IQR 20-54) and 94% were virologically suppressed at initiation of LA CAB/RPV. After a median of 8 doses (IQR 7-9) and for those with follow-up VL, 91 remained suppressed with a VL non-detectable (IQR 0-0). One had a VL of 84 copies/mL. Overall, 21 discontinued therapy, with reasons noted in Table 1. One third discontinued due to financial or payor issues. Non-serious adverse events occurred in 6%, with 4 resulting in discontinuation.ConclusionAn ID physician office based LA CAB/RPV program demonstrated durability in maintenance of virologic suppression with high injection adherence. These results suggest that LA CAB/RPV administered through a standardized ID office-based program is effective in managing HIV-1.DisclosuresNikhil K. Bhayani, MD, FIDSA, Cumberland Pharmaceuticals: Advisor/Consultant|Melinta: Advisor/Consultant|Paratek Pharmaceuticals: Advisor/Consultant Brian S. Metzger, MD, MPH, Abbvie: Advisor/Consultant|Cumberland Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant Richard L. Hengel, MD, FIDSA, Gilead: Grant/Research Support Lucinda J. Van Anglen, PharmD, FIDSA, Cumberland Pharmaceuticals: Grant/Research Support|Ferring Pharmaceuticals: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Novartis: Grant/Research Support|Takeda Pharmaceuticals: Grant/Research Support

Background Oral mucositis/stomatitis is a common adverse event during cancer treatment that can disrupt oral functioning and adherence to treatment. Datopotamab deruxtecan (Dato‐DXd), a TROP2‐directed antibody‐drug conjugate, has shown promise in treating solid tumors. It has been associated with oral mucositis/stomatitis in clinical trials for breast and lung cancer (TROPION program). Currently, there is a lack of formalized guidelines for managing Dato‐DXd‐associated oral mucositis/stomatitis. The present study employed a modified Delphi approach to establish expert consensus on preventing, diagnosing, monitoring, and treating oral mucositis/stomatitis secondary to Dato‐DXd and to improve patient care and clinical outcomes. Materials and Methods A four‐stage modified Delphi study engaging 15 oncology experts from Europe and Canada was used to establish consensus on managing Dato‐DXd‐induced oral mucositis/stomatitis in lung and breast cancer patients. Experts were selected based on their roles as investigators in Dato‐DXd clinical trials, including but not limited to TROPION‐PanTumor01, TROPION‐Lung01, TROPION‐Lung05, and TROPION‐Breast01, and their experience managing cancer treatment–associated oral mucositis/stomatitis. The Delphi process included an initial meeting, two anonymized surveys, an in‐person consensus meeting, and virtual one‐to‐one sessions for absentees. Results Expert consensus was reached on recommendations for managing Dato‐DXd‐associated oral mucositis/stomatitis, and experts highlighted the importance of establishing guidance to improve patient quality of life and clinical outcomes. Key recommendations included prophylactic dexamethasone mouthwash, patient education, and behavioral changes. Early detection through self‐checks and monitoring was emphasized, and recommended treatment strategies were tailored to oral mucositis/stomatitis severity. Treatment recommendations included dose modifications and discontinuation for severe cases. Conclusions This study offers expert guidance on managing Dato‐DXd‐associated oral mucositis/stomatitis, filling a crucial gap in patient care. Ongoing efforts to generate Dato‐DXd‐specific data will facilitate the creation of standardized, evidence‐based protocols to improve patient safety and treatment outcomes.

BackgroundInfertility is an underrecognized disease which affects over 17% of the reproductive age population worldwide. However, availability of, and access to, assisted reproductive technology (ART) is variable across countries. There are significant challenges relating to awareness, financial and other barriers to care, cultural considerations, and the level of support provided to people undergoing care. Previous studies have explored these challenges, but less attention has been given to the policy implications. As the need for fertility care rises, we investigate the evidence that policy changes can be implemented to improve access to ART treatment.MethodsA review of literature was conducted on fertility policy challenges and developments, covering fertility recognition and awareness; cultural and religious considerations; and access to ART treatment, psycho-social care, and supplementary care. Nine medical and academic experts were invited to validate secondary research findings and provide their perspectives on policy implications. The experts covered different specialties and geographic expertise. Experts participated in individual 60-minute interviews, then a half-day Policy Forum discussion was held virtually in May 2023.ResultsLack of recognition of infertility as a disease, low financial coverage of fertility services, limited psychosocial support, and cultural considerations are substantial barriers to fertility services access. Some countries have limited reimbursement of services or offer only private care, significantly limiting treatment access. Others restrict reimbursement based on age, gender and family status, which creates access inequities. Policy action is needed to mitigate these challenges and to ensure timely and equitable access to fertility care. Decision-makers need to collectively recognize infertility as a disease, rather than just a social issue. Equity of access to infertility services should be ensured by expanding the availability of public funding, along with review and rationalisation of criteria for treatment reimbursement. To improve engagement in treatment and support through the fertility journey, access to psychosocial care should be expanded and included as a core service.ConclusionMajor obstacles to accessing ART treatment have been identified across regions globally, highlighting the urgent need for national policy action to enhance care quality by reviewing current legislation, improving patient and physician education, refining reimbursement procedures, and expanding psychosocial support services.

Does obscenity law affect moral values and does it matter? Using random judge assignment and all U.S. obscenity precedents since 1958, we report four key findings. Democratic judges, more than Republicans, tended to vote progressively in obscenity cases. Such progressive rulings liberalized sexual attitudes and behaviors, increased asymptomatic STDs, but reduced child abuse. The media played a role in transferring legal precedents onto societal values. These results support a model positing laws not only sanction activities but also shape societal norms, especially when these activities become prevalent.

This floor pen study explored the effects of feeding mineral methionine hydroxyl analogue chelates (MMHACs) zinc (Zn), copper (Cu), and manganese (Mn) on growth performance, carcass processing weight and quality, nutrient digestibility, gizzard erosion score, and bone parameters of broilers. One-day-old Ross 308 male chicks (n = 384) were randomly allocated to four dietary treatments with eight replicate pens per treatment and 12 birds per pen. The treatments were as follows: (1) inorganic trace mineral ZnSO4 110 ppm, CuSO4 16 ppm, MnO 120 ppm (ITM); (2) MMHAC Zn 40 ppm, Cu 10 ppm, Mn 40 ppm (M10); (3) Inorganic trace mineral ZnSO4 110 ppm, tribasic copper chloride 125 ppm, MnO 120 ppm (T125); (4) MMHAC Zn 40 ppm, Cu 30 ppm, Mn 40 ppm (M30). The birds were fed nutritionally complete wheat sorghum soybean meal-based diets from days 0 to 42 with three feeding phases including starter (days 0-10), grower (days 10-21), and finisher (days 21-42). The findings revealed that birds on the T125, M10, and M30 groups possibly had higher feed intake (p = 0.052) and higher weight gain (p < 0.063) than birds on the ITM group from days 0 to 42. Furthermore, birds fed the M30 diet had higher thigh and drumstick weights compared to those fed the ITM diet at day 42 (p = 0.05). Additionally, birds offered the M30 diet had increased ileal Cu digestibility compared to birds offered the M10 and ITM diets at day 21 (p = 0.006). Gizzard erosion scores and bone parameters were similar between the dietary treatments. Hence, the supplementation of MMHACs to broiler diets at 30 ppm may be a more suitable strategy to increase weight gain and the thigh and drumstick processing weight while maintaining the bone health of broiler chickens.