Participation of Older Adults in Clinical Trials for New Drug Applications and Biologics License Applications From 2010 Through 2019.

Importance: Older age may be accompanied by changes in the pharmacokinetics or pharmacodynamics or both of medications that can result in altered safety and efficacy profiles. Objective: To assess representation of older adults in clinical trials of new drug applications (NDAs) and biologics license applications (BLAs). Design, Setting, and Participants: This cross-sectional study analyzed US Food and Drug Administration (FDA) data for NDAs and BLAs approved from 2010 through 2019. Age distribution of clinical trial participants was compared with age distribution of the US population with the disease or disorder (prevalent population). Data were from adults enrolled in registration trials for depression, heart failure, insomnia, non-small cell lung cancer (NSCLC), nonvalvular atrial fibrillation (NVAF) stroke prevention, osteoporosis, and type 2 diabetes or adults sampled from US prevalent population in community-dwelling health data. Data were analyzed from November 2020 to February 2021. Exposures: Trial enrollment. Main Outcomes and Measures: Representativeness of trial populations was assessed by the participation to prevalence ratio (PPR) defined as the percentage of patients by age group among clinical trial participants to the percentage of patients by age group among US prevalent population. Results: Data from 166 clinical trials (229 558 participants) for 44 NDAs and BLAs were analyzed. The most consistent finding was the limited enrollment of the oldest age groups, namely those 75 years and above for type 2 diabetes and NSCLC, and 80 years and above for NVAF stroke prevention, insomnia, heart failure, and osteoporosis. Adults aged 60 to 74 years were enrolled in equal or greater proportion than the US prevalent population. Conclusions and Relevance: In this cross-sectional study, underrepresentation of the oldest adults existed during evaluation of new drugs and biologics, yet the older adults may represent significant proportions of the treatment population. Closing the representation gap between clinical trial enrollment and potential treatment populations is essential for safe and effective use of new drugs and biologics.

Clinical pharmacology information in regulatory submissions and labeling: A comparative analysis of orphan and non-orphan drugs approved by the FDA.

Clinical pharmacology is an integral discipline supporting the development, regulatory evaluation, and clinical use of drugs for the treatment of both common and rare diseases. Here, we evaluated the recommendations and information available from select clinical pharmacology studies in the therapeutic product labeling of new molecular entities (NMEs) approved from 2017 to 2019 for both common and rare diseases. A total of 151 NMEs, including 72 orphan and 79 non-orphan drugs, were analyzed for recommendations and information available related to food-drug interaction, drug-drug interaction, renal impairment, hepatic impairment, QT assessment, and human radiolabeled mass balance studies using data collected from the original labeling and other regulatory documents. The analysis showed no statistically significant difference in the recommendations between orphan and non-orphan drugs except for renal impairment related recommendations in section 8 of the labeling. Although not significant, fewer hepatic impairment labeling recommendations were available for orphan drugs when compared with non-orphan drugs. At the time of initial approval, 79 postmarketing requirements (PMRs) and postmarketing commitments (PMCs) for 33 orphan drugs and 39 PMRs and PMCs for 19 non-orphan drugs were established; with most difference observed for drug-drug interaction, hepatic impairment, and QT assessment. Overall, although there was a trend for more labeling recommendations and fewer postmarketing studies and clinical trials for non-orphan drugs, there appeared to be no substantial differences in how these select clinical pharmacology studies are leveraged during the development and approval of orphan and non-orphan drugs.

Using Social Media to Enhance Provider Network for HIV and Harm Reduction Service Integration in Vietnam.

Social media can potentially serve as a platform to coordinate medical care among fragmented health sectors. This paper describes procedures of using social media to enhance antiretroviral therapy (ART) and methadone maintenance treatment (MMT) providers' virtual network for integrated service for HIV-positive people who inject drugs (PWID) in Vietnam. A total of 88 ART and MMT treatment providers participated in person group sessions followed by online virtual support to improve service integration. In-person reunions were held to reinforce Facebook participation and network activities. Content analysis was used to identify keywords and topic categories of the online information exchange. Both MMT and ART providers were actively engaged in online communications. Referral and treatment adherence were the two most frequently discussed topic areas by both the MMT and ART providers. Frequent cross-agency connections were observed. Online provider networks and communities could be built and useful to support treatment providers to improve service integration.

An intervention trial targeting methadone maintenance treatment providers to improve clients' treatment retention in China.

BACKGROUND: Service providers including doctors, nurses, and other healthcare professionals play an essential role in methadone maintenance treatment (MMT). This study evaluated the impact of an intervention targeting MMT providers on their clients' treatment retention. METHODS: This study was conducted in 68 MMT clinics in five provinces of China with 36 clients randomly selected from each clinic. The clinics were randomized to intervention or control condition. The MMT CARE intervention started with group sessions to enhance providers' communication skills. The trained providers were encouraged to conduct individual sessions with clients to promote treatment engagement. The outcomes, which include client retention (main outcome) and their reception of provider-delivered individual sessions (process outcome), were measured over a 24-month period. RESULTS: Significantly fewer intervention clients dropped out from MMT than control clients during the study period (31% vs. 41%; p < 0.0001). Dropout hazard was significantly lower in the intervention condition compared to the control condition (HR = 0.71, 95% CI: 0.57, 0.89). More intervention clients had individual sessions than control clients (93% vs. 70%; p < 0.0001). Having individual sessions was associated with a significantly lower dropout hazard (HR = 0.30, 95% CI: 0.23, 0.40). The intervention clients had a significantly lower dropout hazard than the control clients if they started the individual sessions during the first six months (HR = 0.68, 95% CI: 0.51, 0.90). CONCLUSIONS: The MMT CARE intervention focusing on provider capacity building has demonstrated efficacy in reducing clients' treatment dropout. This study sheds light on MMT service improvement in China and other global community-based harm reduction programs.

Family Related Factors and Concurrent Heroin Use in Methadone Maintenance Treatment in China.

BACKGROUND: The use of heroin during Methadone Maintenance Treatment (MMT) is a challenging problem that contributes to poor treatment outcomes. Families may play an important role in addressing concurrent heroin use during MMT, especially in collectivist societies such as China. OBJECTIVES: In this study, we explored the relationship between family-related factors and concurrent heroin use during MMT in China. METHODS: This study was conducted at 68 MMT clinics in five provinces of China. There were 2,446 MMT clients in the analysis. Demographic information, MMT dosage, family members' heroin use status, family support of MMT, family problem, and self-reported heroin use were collected in a cross-sectional survey. The most recent urinalysis of opiate use was obtained from clinical records. RESULTS: Of the 2,446 participants, 533 (21.79%) self-reported heroin use in the previous seven days or had a positive urine morphine test result in the clinic record. Participants whose family member[s] used heroin were 1.59 times (95% CI: 1.17, 2.15) more likely to use concurrently during treatment. Those with family members who totally support them on the MMT were less likely to use (AOR: 0.75, 95% CI: 0.60, 0.94). Having more family problems was positively associated with concurrent heroin use (AOR: 2.01, 95% CI: 1.03, 3.93). CONCLUSIONS: The results highlight the importance of the family's role in concurrent heroin use during MMT programs. The study's findings may have implications for family-based interventions that address concurrent heroin use.

Efficacy of a multilevel intervention on the mental health of people living with HIV and their family members in rural China.

OBJECTIVE: HIV has a profound impact on infected individuals and their families. This study evaluated the efficacy of an intervention aimed at improving the mental health of people living with HIV (PLH) and their family members. METHOD: A randomized controlled trial of 475 PLH and 522 family members was conducted in Anhui, China. The intervention comprised activities at individual, family, and community levels. The study outcomes, which included depressive symptoms and coping with illness for the PLH and depressive symptoms and caregiver burden for the family members, were assessed at baseline and at 6-, 12-, 18-, and 24-month follow-up. We used a mixed-effects regression model with village- and participant-level random effects to assess the intervention effect on the improvement of outcome measures. RESULTS: Relative to the control condition, the PLH and family members of the intervention group reported a significant reduction in depressive symptoms. The largest difference in depressive symptoms was observed at 6 months for the PLH and at 12 months for family members. Decreases in perceived caregiver burden over time were observed for family members in both conditions; however, the group difference did not reach statistical significance. Significant intervention effect on the coping with illness was reported by the PLH. CONCLUSIONS: The study highlights the importance of empowering families affected by HIV to confront the challenges together rather than individually. It may be optimal for future programs to include both PLH and their family members to maximize intervention effects through strengthening interactions and support within a family. (PsycINFO Database Record

Spousal role and caregiver burden in HIV affected families in Anhui Province, China.

This study examined the burden experienced by various roles of family caregivers of people living with HIV (PLH), in particular spouses vs. non-spouses. A total of 475 family members of PLH were recruited from Anhui Province, China. Participants responded to a survey using the Computer Assisted Personal Interview method. The assessment collected data on demographic characteristics and their perceived caregiver burden, which was compared between spouses and non-spouses. Multiple regression models were built to identify factors associated with caregiver burden. About 64.4% of our study participants were female and the mean age was 42.1 years. Among various relationships to PLH, almost half reported being a spouse. Spouses reported significantly higher caregiver burden than non-spouses. In addition, older age and lower family income were significantly associated with higher level of caregiver burden. Among the subsample of spouses, significantly higher level of caregiver burden was identified among wives. Future studies should give special consideration to address the needs of female spouses in order to reduce their caregiver burden.

Factors related to client satisfaction with methadone maintenance treatment in China.

BACKGROUND: This study examined clients' treatment satisfaction with the services provided by methadone maintenance treatment (MMT) in China and explored relevant factors that are directly or indirectly associated with treatment satisfaction. METHODS: The study used baseline data from a randomized controlled trial conducted among 2,448 clients from 68 MMT clinics in five provinces of China. The participants reported their demographic characteristics, treatment-related factors, depressive symptoms, treatment progression, counseling rapport, and treatment satisfaction. Structural equation modeling (SEM) was used to test the direct and indirect relationships among various factors and treatment satisfaction. RESULTS: Clients' demographic characteristics, such as older age, had both a direct effect on treatment satisfaction and an indirect effect mediated by counseling rapport. Depressive symptoms and a lack of social support had a direct negative impact on treatment satisfaction and an indirect effect mediated by treatment progression and counseling rapport. Both mediators: treatment progression (estimate=0.227, p<0.01) and counseling rapport (estimate=0.229, p<0.01), showed positive associations with treatment satisfaction. CONCLUSION: The findings reiterate the complex nature of MMT clients' treatment satisfaction and its interrelationship with multidimensional factors. The study has implications for evaluating the quality of care provided by MMT programs and suggests several strategies that can potentially improve MMT clients' level of treatment satisfaction.

Self-reported sexually transmitted disease symptoms and treatment-seeking behaviors in China.

In recent decades, sexually transmitted diseases (STDs) have reemerged and spread as a major public health problem in China. However, little effort has been made on promoting appropriate health-seeking behaviors among people living with STDs. A randomly selected sample of market vendors in Fuzhou (N = 4510) was recruited and assessed from 2003 to 2004 to examine their choice of pharmacy versus hospital, and folk remedy versus Western medicine when having STD symptoms. Approximately 11.3% of the sample (4.0% of men and 17.8% of women) reported having had abnormal genital discharge or genital ulcer during the past 6 months. More (over 60%) people chose Chinese folk remedy to treat symptoms or prevent transmission when they had genital discharge and/or genital ulcer. Approximately 30% of study participants with reported STD symptoms visited pharmacies only to seek treatment, and 17% visited neither hospital nor pharmacies. Visiting a pharmacy only for STD treatment was marginally significantly associated with being female (prevalence ratio [PR] = 1.665, confidence interval [CI] = 0.980, 2.831) and never married (PR = 1.984, CI = 1.098, 3.594) after controlling for other potential confounders. Education about appropriate health-seeking behaviors to obtain effective treatment of STD must be a top priority to control the rapid spread of STDs in China.

Sexually transmitted diseases and risk behaviors among market vendors in China.

OBJECTIVES: The rate of sexually transmitted diseases (STDs) in China has soared over the past 20 years. There is a need to study STD prevalence in the general population of the country. GOAL: To report the prevalence and patterns of STDs and the relationships between STD status and demographic and behavioral factors. STUDY DESIGN: A total of 4,510 market vendors in a city in eastern China were interviewed and tested for STDs. RESULTS: The prevalence of any STD among participants was 16.55% (women, 21.04%; men, 11.54%). Among those who tested positive for an STD, chlamydia was most common (8.89%), followed by herpes (6.50%). Participants who had no schooling and participants who had college or higher level of schooling had a similarly high STD prevalence (26.19% vs. 24.00%, respectively). Prevalence of all STDs was significantly higher among women, those with more discretionary income, and those with multiple partners. CONCLUSIONS: Special considerations are needed for low versus high education groups as well as men versus women to maximize the effects of STD prevention programs and messages in China.