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References | PMC9932095 | |||
Background | SUD | DISORDERS | Individuals with substance use disorders (SUD) have disproportionately high rates of unintended pregnancy. Reducing harm associated with this risk and its biopsychosocial consequences requires evidence-based, non-coercive interventions that ensure access to contraception for individuals who choose to prevent pregnancy. We examined feasibility and impact of SexHealth Mobile, a mobile unit-based intervention that aimed to increase access to patient-centered contraceptive care for individuals in SUD recovery programs. | PMC9986654 |
Methods | We conducted a quasi-experimental study (enhanced usual care [EUC] followed by intervention) at three recovery centers with participants ( | PMC9986654 | ||
Results | Participants (median age = 31, range 19–40) enrolled in the intervention period were almost 10 times more likely to be using contraception at one-month (51.5%) versus the those enrolled in the EUC period (5.4%) (unadjusted relative risk [URR] = 9.3 [95%CI: 2.3–37.1]; adjusted relative risk [ARR] = 9.8 [95%CI: 2.4–39.2]). Intervention participants were also more likely to be using contraception at 2-weeks (38.7% vs. 2.6%; URR = 14.3 [95%CI: 2.0–104.1]) and three-months (40.9% vs. 13.9%; URR = 2.9 [95% CI: 1.1–7.4]). EUC participants reported more barriers (cost, time) and less confidence in preventing unintended pregnancies. Mixed-methods feasibility data indicated high acceptability and feasible integration into recovery settings.
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Keywords | PMC9986654 | |||
Introduction | SUD | DISORDERS | Ensuring access to contraception is critical for populations at high risk for unintended pregnancies, particularly those in states with restricted abortion access. Women with a history of substance use disorders (SUD) have long suffered disproportionately high rates of unintended pregnancies. A nationally representative sample of women reported a 70% increased likelihood of unintended pregnancy among women with preconception illicit or recreational drug use, compared to those with no drug use [Women with history of SUD often desire contraception but face access barriers [Entry into recovery services is an opportune time to help individuals meet unmet contraception desires. While contraception access is important at all stages of SUD including recovery, women describe recovery initiation as a time of peak readiness to address broader health needs. Further, women initiating recovery generally state they prefer to plan pregnancies for a time when they have reached stable, long-term recovery [Although some studies have shown increased contraceptive use with SUD recovery-based interventions, they have had limitations [We designed an intervention, | PMC9986654 |
Methods | We conducted a quasi-experimental study with an interrupted time series design (i.e., enhanced usual care [EUC] followed by intervention). We compared contraception use one-month after enrollment among participants enrolled in the two different time periods. The study was approved by The Institutional Review Board at Children’s Mercy Kansas City. | PMC9986654 | ||
Procedures | Study staff worked with recovery centers to share information about the study and visited each site periodically for eligibility screening and enrollment. Interested clients were screened individually by study staff and those eligible provided written informed consent. Site visits continued until the sample size target for each time period (All participants completed a 15-min baseline questionnaire via REDCap that included demographic, substance use, and reproductive health history. For the EUC period (Aug–Nov. 2020), we created a printed information sheet that listed community locations where each recovery center would typically recommend clients contact to access contraception care. By formalizing this contact sheet and offering it to women after the baseline questionnaire on reproductive health needs, we “enhanced” recovery centers’ usual care procedures for reproductive health. In the | PMC9986654 | ||
Outcome measures | PMC9986654 | |||
Primary and secondary outcomes | The primary outcome was use of IUD or hormonal contraception (pills, patch, ring, contraception injection, subdermal implant) at one-month post-enrollment. Secondary outcomes were use at two-weeks and three-months. We also explored group differences in confidence in preventing unintended pregnancy at post-intervention and as a change from baseline to post-intervention (reported on a repeated 5-point scale ranging from “not at all confident” to “extremely confident”) as well as reasons for non-use at one-month (including reasons for not attending clinic visits, picking up prescriptions, and/or starting birth control). | PMC9986654 | ||
Data analysis | REGRESSION, SECONDARY | Descriptive analysis was carried out for all variables, with comparisons made between groups with Chi-Square or Fisher’s Exact tests for categorical variables as appropriate based on cell values, and two-sided independent t-test for continuous variables. We compared groups as intention-to-treat on the primary and secondary outcomes using Fisher’s Exact test and Poisson regression with robust standard errors (unadjusted and adjusted). The adjusted model included demographic factors known to influence contraception use or identified as having influence through a series of bivariate associations with contraception use, including recovery site (residential vs. outpatient), pregnancy intention (trying to avoid/wouldn’t mind avoiding vs. other), pregnancy history (ever been pregnant vs. not) and recency of substance use (defined as use within the three months prior to baseline vs. none). We analyzed the primary outcome again including participants who had missed the one-month assessment but reported a contraception injection (which protects for three months) at post-intervention or two weeks. Quantitative analyses were completed in SAS Version 9.4. (SAS Institute, Cary, NC). Field notes were analyzed with qualitative coding to identify facilitators and barriers according to Bowen’s feasibility constructs [ | PMC9986654 | |
Results | PMC9986654 | |||
Contraception use | For our primary outcome, 51.5% (17/33) of participants in the intervention period were using contraception at one-month post-baseline compared to 5.4% (2/37) in the EUC period (Fishers exact test Likelihood of contraception use at one-month remained high after adjusting for age, recovery center type, pregnancy intention, pregnancy history, and substance use at three-months (adjusted relative risk (ARR) = 9.8 [95%CI: 2.4–39.2]; | PMC9986654 | ||
Confidence and barriers | Self-reported confidence in one’s own ability to protect against unwanted pregnancy (dichotomized as “very/extremely confident” and “not confident/low confident/not sure”) was more prevalent in the intervention than the EUC group in the post-intervention survey (90% vs. 70%; The most frequently cited reason for non-use of contraception at one-month among both groups was “decided did not want/need birth control” (EUC = 27.1%; intervention = 16.0%; | PMC9986654 | ||
Limitations | In this quasi-experimental design, participants were not randomized to conditions. The similarities in both groups on demographic factors proximally associated with contraception use, and the fact that all were recruited from the same sites, however, minimizes the possibility that differences observed between intervention/EUC conditions could be attributed to baseline participant characteristics. The EUC and intervention periods also occurred at different time points, thus there may have been inherent benefits to the intervention period occurring later (e.g., more exposure at each site to sexual health information/activities related to the study). We do not believe that the trajectory of the COVID-19 pandemic had a significant impact on results, as we did not initiate enrollment in the EUC period until in-person activities at recovery centers and referral health centers had resumed. In reporting barriers to contraception, just one participant in the EUC period named a COVID-19 related factor. We also note limitations in diversity in our sample as the majority of our sample identified as white and non-Hispanic.
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Acknowledgements | The authors would like to thank all the implementing partners that made this project possible, especially Rachel Melson, Jennifer Frost, Lori Glenski, Angel Modersohn, DeAnte Hurd, Amanda Derington, Sarah Knopf-Amelung, Olivia Deeken, Mollee Flores, Renee Harris, Erin Hestand, Kelli Hubbard, Bobbi Jo Reed, Jesse Ibarra, Alex Irvin, Brenda Peters, and Alyssa Ibarra. We would also like to thank Beth Canipe and Evelyn Donis de Miranda for help with data collection and manuscript preparation, and all the participants who gave their time and opinions. | PMC9986654 | ||
Author contributions | EAH | Concept and design: EAH, KG, SFK and MKM. Acquisition, analysis, and/or interpretation of data: All authors. Drafting of the manuscript: EAH. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: JNM. Obtained funding: EAH, KG, MKM, SFK. Administrative and technical support: KPB, AA. Supervision: EAH, MKM. All authors read and approved the final manuscript. | PMC9986654 | |
Funding | Research reported in this work was supported by Organon & Co. The content is solely the responsibility of the authors and does not necessarily represent the views of Organon & Co. The funding source had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript. | PMC9986654 | ||
Availability of data and materials | The datasets used during the current study are available from the corresponding author on reasonable request. | PMC9986654 | ||
Declarations | PMC9986654 | |||
Ethics approval and consent to participate | All participants provided written, informed consent prior to enrollment. The study protocol was approved by the Institutional Review Board at Children’s Mercy Kansas City (#1099). | PMC9986654 | ||
Consent for publication | Not applicable. | PMC9986654 | ||
Competing interests | EAH | EAH and MKM received investigator-initiated grants from Organon & Co for studies on contraception access. All other authors declare no competing interests. | PMC9986654 | |
References | PMC9986654 | |||
Key Points | PMC10077097 | |||
Question | autism | POSITIVE, INTERACTION | Is iBASIS–Video Interaction to Promote Positive Parenting (iBASIS- VIPP) therapy, a preemptive intervention for infants displaying early behavioral signs of autism, a good societal investment from a third-party payer perspective? | PMC10077097 |
Findings | In this economic evaluation of 89 children with follow-up data from an iBASIS-VIPP randomized clinical trial in Australia, the intervention was estimated to cost A $5131 (US $3607) per child and deliver a cost savings of A $10 695 (US $7519) per child (modeled to age 12 years). In addition, for each dollar invested in treatment, the savings in third-party payer costs was estimated to be A $3.08 (US $3.08). | PMC10077097 | ||
Meaning | autism | POSITIVE, INTERACTION | These findings suggest that improvement in child developmental outcomes in the iBASIS-VIPP trial was achieved at an expected net cost savings to the Australian government and that iBASIS-VIPP is a likely good-value societal investment.This economic evaluation assesses the estimated net costs of the iBASIS–Video Interaction to Promote Positive Parenting intervention vs usual care among children with early behavioral signs of autism in Australia. | PMC10077097 |
Importance | autism spectrum disorder, ASD, autism | The growing global prevalence of autism spectrum disorder (ASD) is associated with increasing costs for support services. Ascertaining the effects of a successful preemptive intervention for infants showing early behavioral signs of autism on human services budgets is highly policy relevant. | PMC10077097 | |
Objective | POSITIVE, INTERACTION | To estimate the net cost impact of the iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP) intervention on the Australian government. | PMC10077097 | |
Design, Setting, and Participants | autism | Infants (aged 12 months) showing early behavioral indicators of autism were recruited through community settings into the multicenter Australian iBASIS-VIPP randomized clinical trial (RCT), a 5- to 6-month preemptive parent-mediated intervention, between June 9, 2016, and March 30, 2018, and were followed up for 18 months to age 3 years. This economic evaluation, including cost analysis (intervention and cost consequences) and cost-effectiveness analyses of iBASIS-VIPP compared with usual care (treatment as usual [TAU]), modeled outcomes observed at age 3 through to 12 years (13th birthday) and was conducted from April 1, 2021, to January 30, 2023. Data analysis was conducted from July 1, 2021, to January 29, 2023. | PMC10077097 | |
Exposures | iBASIS-VIPP intervention. | PMC10077097 | ||
Main Outcomes and Measures | autism traits | To project the diagnostic trajectory and associated disability support costs drawing on the Australian National Disability Insurance Scheme (NDIS), the main outcome was the differential treatment cost of iBASIS-VIPP plus TAU vs TAU and disability-related government costs modeled to age 12 years, using a clinical diagnosis of ASD and developmental delay (with autism traits) at 3 years. Costs were calculated in Australian dollars and converted to US dollars. Economic performance was measured through the following: (1) differential net present value (NPV) cost (iBASIS-VIPP less TAU), (2) investment return (dollars saved for each dollar invested, taking a third-party payer perspective), (3) break-even age when treatment cost was offset by downstream cost savings, and (4) cost-effectiveness in terms of the differential treatment cost per differential ASD diagnosis at age 3 years. Alternate values of key parameters were modeled in 1-way and probabilistic sensitivity analysis, the latter identifying the likelihood of an NPV cost savings. | PMC10077097 | |
Results | Of the 103 infants enrolled in the iBASIS-VIPP RCT, 70 (68.0%) were boys. Follow-up data at age 3 years were available for 89 children who received TAU (44 [49.4%]) or iBASIS-VIPP (45 [50.6%]) and were included in this analysis. The estimated mean differential treatment cost was A $5131 (US $3607) per child for iBASIS-VIPP less TAU. The best estimate of NPV cost savings was A $10 695 (US $7519) per child (discounted at 3% per annum). For each dollar invested in treatment, a savings of A $3.08 (US $3.08) was estimated; the break-even cost occurred at age 5.3 years (approximately 4 years after intervention delivery). The mean differential treatment cost per lower incident case of ASD was A $37 181 (US $26 138). We estimated that there was an 88.9% chance that iBASIS-VIPP would deliver a cost savings for the NDIS, the dominant third-party payer. | PMC10077097 | ||
Conclusions and Relevance | disability | The results of this study suggest that iBASIS-VIPP represents a likely good-value societal investment for supporting neurodivergent children. The estimated net cost savings were considered conservative, as they covered only third-party payer costs incurred by the NDIS and outcomes were modeled to just age 12 years. These findings further suggest that preemptive interventions may be a feasible, effective, and efficient new clinical pathway for ASD, reducing disability and the costs of support services. Long-term follow-up of children receiving preemptive intervention is needed to confirm the modeled results. | PMC10077097 | |
Introduction | ASD, autism, Autism, ’s social communication, Autism spectrum disorder, a disability, autistic, repetitive and sensory behaviors, disability, neurodevelopmental disability | POSITIVE, RECRUITMENT, INTERACTION | Autism spectrum disorder (ASD; autism) is the term for a neurodevelopmental disability characterized by qualitative and lifelong challenges in social interaction and communication as well as the presence of repetitive and sensory behaviors and interests.Many countries, including Australia, have reported a marked increase in ASD diagnoses over recent decades, with global prevalence estimates of 1.2% to 2%.The disability associated with ASD has cost implications for familiesA challenge for health and disability systems globally is how to apportion finite funding to best support persons with a disability, including autistic individuals, and their families. Optimization of resource allocation requires an understanding of both the efficacy and efficiency (benefits vs costs) of potential interventions, especially to inform when to intervene. The typical clinical pathway for autistic children is to commence the delivery of interventions at the time of diagnosis. Autism emerges in early development, but diagnosis mostly occurs in the late preschool years worldwide.The iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP) intervention is one such preemptive approach that seeks to support infant development by using video feedback techniques to increase caregiver awareness of their infant’s social communication and to guide caregiver responses to build infant social engagement and interaction.A second trial of iBASIS-VIPPPolicy recommendations rely on a combination of evidence for efficacy and cost-effectiveness—that is, whether observed outcomes represent good value for resources allocated. Consistent with the structured approach for evaluating the iBASIS-VIPP intervention and given evidence of its efficacy and effectiveness (noting a community-based recruitment strategy through maternal and child health nurses and a child development service),The aim of this study was to assess whether iBASIS-VIPP represents an efficient use of societal resources, taking a government (insurer) third-party payer perspective and incorporating several performance measures as follows: (1) cost analysis measured by net present value (NPV), (2) cost-effectiveness analysis (cost per outcome of ASD incident cases), (3) timing of break-even cost (child age when intervention cost was matched by downstream cost savings), and (4) dollars saved per dollar invested. | PMC10077097 |
Methods | PMC10077097 | |||
Overview | The iBASIS-VIPP RCTThis economic evaluation was conducted from April 1, 2021, to January 30, 2023, and drew on (1) the Australian RCT | PMC10077097 | ||
Differential Intervention Cost | The differential intervention cost (iBASIS-VIPP compared with TAU) incorporated all child development–related services delivered during the 6-month intervention period. Data inputs were derived from trial records.The iBASIS-VIPP intervention is a manualized program with a defined number of sessions delivered by suitably qualified and trained staff in participants’ homes. The intervention cost for delivering iBASIS-VIPP included the following: (1) therapy costs, (2) direct travel costs, (3) therapy-related administration costs, and (4) training and supervision costs. First, therapy costs were calculated as the product of the number of sessions delivered by the therapist (introductory, core, booster) and mean hours per session delivered in participants’ homes, plus other therapy-related activities (eg, time to review video material), administrative time (eg, appointment scheduling), and published clinician hourly rates | PMC10077097 | ||
Clinical Outcomes | SECONDARY | The incidence of ASD diagnostic classification at age 3 years (ASD classification vs none) was a secondary outcome of the trial by Whitehouse et al.The diagnostic trajectory of children not meeting the | PMC10077097 | |
Downstream Cost | a disability | Expected downstream support costs were estimated based on diagnostic classification (ASD and DD) combined with published NDIS cost data, noting that the NDIS was established to support persons with a disability to have, as far as possible, “the same things in life as other people,” | PMC10077097 | |
Mean Annual Support Costs Through the Australian National Disability Insurance Scheme by Primary Diagnosis and Age Group, 2021 | Abbreviations: A$, Australian dollars; NA, not applicable.Data are mean payments and utilization of plan budgets from the Australian National Disability Insurance Scheme as of March 2022. | PMC10077097 | ||
NPV Cost and Return on Investment | To estimate NPV costs (or cost savings), differential treatment costs for iBASIS-VIPP vs TAU across the 6-month intervention period were combined with modeled downstream cost savings to age 12 years and discounted at 3% per annum. We also estimated a return on investment, which comprised dollar savings in downstream costs per dollar invested in iBASIS-VIPP treatment. | PMC10077097 | ||
Cost-effectiveness Analysis | We estimated the cost per lower incident case of diagnosed ASD. This was calculated as the differential treatment cost per reduced case meeting the ASD diagnostic criteria at age 3 years.All costs were calculated in Australian dollars. Costs were then converted to US dollars according to the exchange rate on January 24, 2023 (A $1.00 = US $0.703). | PMC10077097 | ||
Sensitivity Analysis | A sensitivity analysis was conducted to explore the estimated NPV cost of plausible adjustments to key parameters ( | PMC10077097 | ||
Parameter Values Incorporated Into Probabilistic Sensitivity Analysis to Estimate Net Present Value Cost Savings of iBASIS–Video Interaction to Promote Positive Parenting vs Usual Care | autism spectrum disorder, Disability | POSITIVE, INTERACTION | Abbreviations: ASD, autism spectrum disorder; CL, confidence limit; DD, developmental delay; iBASIS-VIPP, iBASIS–Video Interaction to Promote Positive Parenting; NA, not applicable; NDIS, National Disability Insurance Scheme; RCT, randomized clinical trial; TAU, treatment as usual.Support costs for eligible children with DD occur up to their seventh birthday as per the Australian NDIS. Beyond that age, a child may be eligible under an alternate disability category, but such uncertainty modeling was not considered appropriate for this study.Noting NDIS costs from published annual payments of A $15 640 (US $10 995) per child at ages 7 to 14 years and A $28 800 (US $20 247) per child at ages 15 to 18 years (Table 1).Alternate values for iBASIS-VIPP and TAU costs were not modeled because an alternate (lower or higher) cost would mean a different clinical service and as such would potentially impact outcomes and costs and outcomes must be considered together.Assumed value (considered plausible based on expert opinion).Category of DD was not diagnostic, but rather included children with some features of ASD, not meeting a threshold for an ASD diagnosis. As such, not all of these children would be eligible for (or need) government supports through the NDIS. Therefore, 50% was taken as a reasonable best estimate drawing on expert opinion on knowledge of these children and NDIS eligibility. In sensitivity analysis, it was assumed that 100% of these children would receive supports.We conducted 1-way sensitivity analyses, reporting the individual effect of modifying each parameter in turn. We also conducted probabilistic sensitivity analysis, describing the combined impact of adjusting all model parameter values simultaneously on NPV cost. In the probabilistic analysis, results are expressed as the percent likelihood that iBASIS-VIPP would be cost saving or achieve any specified cost-savings threshold. Modeling of base-case estimates and 1-way sensitivity analysis was conducted in Excel, version 2302 (Microsoft). Probabilistic sensitivity analysis was performed in TreeAge Pro, version R1.0 (TreeAge Software). Data analysis was conducted from July 1, 2021, to January 29, 2023. The modeling was based on a 2-tailed, 5% | PMC10077097 |
Results | PMC10077097 | |||
Study Participants | Of the 103 infants enrolled in the 2019 iBASIS-VIPP RCT, | PMC10077097 | ||
Cost of Program Delivery | The total cost of iBASIS-VIPP delivery (including TAU services) was estimated at A $5477 (US $3850) per child. For the TAU group, the estimated cost was A $346 (US $243) per child. The cost difference was A $5131 (US $3607) per child. The costs of clinical services, including apportioned training costs, are detailed in | PMC10077097 | ||
Consultations and Health Care Costs Related to Child Development Services by Group Assignment During the 6-Month Trial Intervention Period, 2021 | Autism | POSITIVE, HOLIDAY, INTERACTION | Abbreviations: A$, Australian dollars; iBASIS-VIPP, Video Interaction to Promote Positive Parenting intervention within the British Autism Study of Infant Siblings; MBS, Medicare Benefits Schedule; NA, not applicable; TAU, treatment as usual.The mean iBASIS-VIPP consultation cost per session was A $600.75 (US $422.33). This was calculated using a mean 4.5 hours per session, 1.5 hours for program delivery, 1 hour of driving time, and 2 hours of clinical administration time (video review, arranging appointments, and so on) at A $133.50 (US $93.85) per hour. Hourly cost was based on a mean salary of A $92 000 (US $64 676) plus 20% wage on-costs and 30% overhead, 43 working weeks for the occupational therapist for 52 less 4 weeks of annual leave, 2 weeks of public holiday, 2 weeks of sick leave, and 1 week of other leave and assuming 5 hours of clinic-related time per day.Mean round-trip distance of 20 km/session and A $0.72 (US $0.51) per kilometer.The cost for a laptop computer, video camera plus accessories, and toys was A $750 (US $527) per clinician × 4.Accessed in December 2021. A clinician may charge more than the schedule fee; the group workshop session fee is for group therapy by a psychologist. Allied health is MBS item 82010 or item 82020 for an occupational therapist, speech pathologist, or physiotherapist.See eAppendix 2 in The mean cost for clinical services was A $5059 (US $3556) per child in the iBASIS-VIPP group and A $346 ($243) per child in the TAU group, delivering a mean number of 12.3 and 3.8 services per child, respectively. Costs of training and supervision for iBASIS-VIPP were estimated at A $83 544 (US $58 731) and A $418 (US $295) per child. | PMC10077097 |
Clinical Outcome | As reported previously by Whitehouse et al, | PMC10077097 | ||
Downstream Costs for Disability-Related Services | best-estimate | The best-estimate discounted downstream support costs were A $20 707 (US $14 557) for the iBASIS-VIPP group and A $36 533 (US $25 683) for the TAU group. This was a lower mean cost of A $15 826 (US $11 126) per child for iBASIS-VIPP. | PMC10077097 | |
Economic Performance | PMC10077097 | |||
Cost-effectiveness and NPV | In terms of cost-effectiveness, the estimated cost per reduction in an ASD diagnosis at age 3 years was A $37 181 (US $26 138). When modeled to age 12 years, NPV cost savings were estimated at A $10 695 (US $7519) per child enrolled in iBASIS-VIPP (A $15 826 less A $5131 treatment cost differential; | PMC10077097 | ||
Downstream Costs and Net Present Value Cost Savings of iBASIS–Video Interaction to Promote Positive Parenting, Best Estimate and 1-Way Sensitivity Analysis | autism spectrum disorder, Disability | Abbreviations: A$, Australian dollars; ASD, autism spectrum disorder; CL, confidence limit; DD, developmental delay; NDIS, National Disability Insurance Scheme; NPV, net present value. | PMC10077097 | |
Break-Even Cost and Return on Investment | We estimated that the cost of iBASIS-VIPP to the third-party payer (NDIS) would be offset by downstream savings at age 5.3 years, or 4 years after delivery of the preemptive intervention. By age 13 years, we estimated a savings to the third-party payer of A $3.08 (US $3.08) for each A $1.00 (US $1.00) invested in iBASIS-VIPP program delivery (A $15 826 divided by A $5131). | PMC10077097 | ||
Sensitivity Analysis | Results of the 1-way sensitivity analysis are reported in | PMC10077097 | ||
Probabilistic Sensitivity Analysis of Estimated Net Present Value Cost Savings per Child for the iBASIS–Video Interaction to Promote Positive Parenting Intervention vs Usual Care | On the x-axis, negative values indicate additional cost and positive values indicate cost savings. Dollars are expressed as Australian dollars. The vertical dashed line indicates the break-even point.From the probabilistic sensitivity analysis, we estimated an 89% likelihood that NPV is at least 0—that is, downstream cost savings at least equal to intervention cost. This means there was an 88.9% chance that iBASIS-VIPP would deliver costs savings (or no net cost impost) for the NDIS, the dominant third-party payer. The likelihood of generating at least any specified cost savings (read off the x-axis) is described by the y-axis ( | PMC10077097 | ||
Discussion | ’ disability, disability, autism | To our knowledge, this is the first economic evaluation of a preemptive intervention for infants showing early behavioral signs of autism. This study drew on data from a high-quality RCTA conservative approach to modeling downstream costs was adopted, including only third-party payer costs of the national disability insurer for disability supports and modeled to the 13th birthday. The analysis did not incorporate broader psychosocial and economic impacts (eg, labor force participation among parentsThere has been considerable discussion within the neurodevelopmental science community about the potential efficacy of preemptive interventions that focus on antecedent neurodevelopmental trajectories,There may be potential for improved efficiencies in iBASIS-VIPP delivery, such as in a clinical setting or a combination of clinic, home-based, and telehealth delivery.An assumption of our model concerned stability of ASD diagnosis—specifically, that 87% of children with an ASD diagnosis at age 3 would carry that diagnosis into middle childhood. This assumption was considered well supported because it was based on 2 high-quality studies.The current study has a number of design strengths. The study drew on high-quality clinical research data from an RCT that had 2 years of participant follow-up and replicated findings of a previous RCT. Downstream cost consequences relied on well-characterized published national data from a single-payer disability insurance system, in which the scope of services and supports must relate directly to participants’ disability. As such, payments made under the NDIS provide a reasonably comprehensive estimate of the cost to the human services sector of supporting disability associated with ASD—an approach to the estimation of cost consequences that is not available in other health systems. Estimated benefits are considered conservative in excluding some government, societal, and family costs and impact on quality of life. | PMC10077097 | |
Limitations | autistic, disability | This study had a number of limitations. The study population enrolled in the RCT was somewhat advantaged relative to the Australian population in terms of maternal education (60% of parents in the RCT had a bachelor’s degree or higher vs 43% of Australian women aged 25-34 yearsThis study estimated potential cost savings in a national setting (Australia), facilitated by the existence of a national disability insurer. The generalizability of these findings to other contexts will depend on service supports available to autistic children. Repeating this study in other jurisdictions would be informative. | PMC10077097 | |
Conclusions | The findings of this economic evaluation, combined with previous clinical trial evidence, | PMC10077097 | ||
Objective | obese, overweight, T2DM, Diabetes, weight loss | OBESE, DISEASE, TYPE 2 DIABETES MELLITUS, DIABETES | Edited by: Sen Li, Beijing University of Chinese Medicine, ChinaReviewed by: Ping Jin, Third Xiangya Hospital, Central South University, China; Wei Wu, Guangdong Provincial Center for Disease Control and Prevention, China†These authors have contributed equally to this work and share first authorshipThis article was submitted to Clinical Diabetes, a section of the journal Frontiers in EndocrinologyPolyethylene glycol loxenatide (PEG-Loxe) is a novel, once-weekly glucagon-like peptide 1 receptor agonist that is approved in doses of 0.1 mg and 0.2 mg for the treatment of type 2 diabetes mellitus (T2DM). However, no clinical trials have been designed to determine the effect of 0.3 mg PEG-Loxe on weight loss in overweight or obese patients with T2DM. This trial aimed to evaluate the short-term effect of 0.3 mg PEG-Loxe, injected subcutaneously once weekly, for weight management in overweight or obese patients with T2DM. | PMC9909427 |
Methods | overweight or obese, T2DM | This 16-week, open-label, parallel-arm, randomized, metformin-controlled trial was conducted at Shandong Provincial Hospital in Shandong, China. Patients with T2DM, who were overweight or obese (body mass index ≥ 25.0 kg/m | PMC9909427 | |
Results | Weight loss | Overall, 156 patients were randomized and exposed to treatment. Weight loss was 7.52 kg (8.37%) with PEG-Loxe and 2.96 kg (3.00%) with metformin, with a between-group difference of 4.55 kg (95% CI, 3.43 to 5.67) ( | PMC9909427 | |
Conclusion | obese, overweight, T2DM, weight loss | OBESE | In overweight or obese patients with T2DM, a once-weekly subcutaneous administration of PEG-Loxe for 16 weeks, in addition to lifestyle interventions or oral antidiabetic drug therapy, resulted in significantly greater weight loss compared to metformin. Additional trials are necessary to establish whether these effects can be maintained in the long term. | PMC9909427 |
Clinical trial registration | PMC9909427 | |||
Introduction | anti-PEG-Loxe, weight gain, overweight, weight loss, T2DM | TYPE 2 DIABETES MELLITUS, OBESE, SIDE EFFECT | Type 2 diabetes mellitus (T2DM) is commonly associated with being overweight or obese. In China, more than half of patients with T2DM are overweight or obese (Weight management is a vital aspect of treatment for patients with T2DM. However, weight gain is a side effect of some antidiabetic drugs, including thiazolidinedione, sulfonylurea, glinide, and insulin (GLP-1RAs are a relatively new class of drugs used to treat T2DM in the general population. The primary function of GLP-1RA is to improve glucose metabolism by increasing pancreatic β-cell insulin secretion and reducing α-cell glucagon secretion. Another well-known effect of GLP-1RA is weight loss through appetite suppression and reduced food intake (Polyethylene glycol loxenatide (PEG-Loxe) is a novel GLP-1RA derived from exendin-4, with 53% homology to human GLP-1 and an anti-PEG-Loxe antibody positive rate of < 2% ( | PMC9909427 |
Materials and methods | PMC9909427 | |||
Trial design and participants | T2DM | This 16-week, open-label, parallel-arm, randomized, metformin-controlled trial was conducted between March 2022 and October 2022 at the Department of Endocrinology, Shandong Provincial Hospital, Shandong, China. The Ethics Committee of Shandong Provincial Hospital approved the trial protocol (No. 2022-046/February 2022), which complied with the Declaration of Helsinki. Written informed consent was obtained from all the participants. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2200057800).Key inclusion criteria included T2DM diagnosis (according to the 1999 World Health Organization criteria) ( | PMC9909427 | |
Randomization and masking | Eligible patients were randomly assigned using an Interactive Web Response System in a 2:1 ratio to receive 0.3 mg PEG-Loxe (Hansoh Pharma) or 1500 mg metformin (Merck). Randomization was stratified according to the following two variables:BMI: 25.0–29.9 kg/mPre-trial treatment: lifestyle interventions or OAD therapy.Moreover, the clinical trial statistician was blinded to the two groups during data analysis. | PMC9909427 | ||
Procedures | ADVERSE EVENTS, INSULIN SENSITIVITY | PEG-Loxe or metformin was added to the current treatment regimen of each patient: OAD therapy or lifestyle interventions. PEG-Loxe was injected subcutaneously once weekly. This treatment followed a fixed-dose-escalation regimen: an initial dose of 0.1 mg for 4 weeks, followed by 0.2 mg for 4 weeks, then a maintenance dose of 0.3 mg for 8 weeks. Similarly, a metformin maintenance dose of 1500 mg was administered in 500 mg weekly increments from 500 mg to 1500 mg.In cases where the baseline HbA1c level was Patient visits were at 4, 8, and 16 weeks, and they included physical examination and data collection. The following information was obtained: demographic data, medical history, vital signs, visceral fat area (VFA), and laboratory test results. Laboratory tests included those for HbA1c, fasting plasma glucose (FPG), C-peptide, lipid profile, and liver function. Additionally, any adverse events (AEs) were recorded. For weight measurement, patients were instructed to remain in the fasting condition, wear light clothing, and take off their shoes. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate were measured using a blood pressure monitor (HEM-7312; OMRON, Kyoto, Japan). VFA was assessed using bioelectric impedance analysis (InBody 720, Seoul, South Korea). Fasting blood samples were collected in the morning and analyzed at the Clinical Laboratory of Shandong Provincial Hospital. β-cell function (HOMA-B) and insulin sensitivity (HOMA-S) were estimated using FPG and fasting C-peptide in an updated Homeostasis Model Assessment (HOMA2) obtained from the University of Oxford database ( | PMC9909427 | |
Endpoints | weight loss, hypoglycemic, TG | EVENTS, SECONDARY | Endpoints were collected at week 16, and the primary endpoint was a change in body weight. The secondary endpoints included the proportion of patients with ≥5% and ≥10% weight loss percentages; and changes in BMI, waist circumference (WC), VFA, HbA1c, FPG, C-peptide, HOMA-B, HOMA-S, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), SBP, and DBP. The safety endpoints included AEs, serious AEs (SAEs), hypoglycemic events, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and pulse rate. | PMC9909427 |
Statistical analysis | weight loss, TG | The planned sample size of 150 patients was randomized 2:1 to receive either PEG-Loxe or metformin. This sample size was expected to provide a power of 80% to detect a difference of ≥2 kg weight loss between the PEG-Loxe and metformin groups, with a standard deviation (SD) of 3.66 (The normal distribution of variables was evaluated using the Kolmogorov-Smirnov test and by assessment of residual distribution. Baseline variables were analyzed using independent t test, Mann-Whitney U test, and χ² test.The efficacy analyses were evaluated using the full analysis set, defined as patients exposed to ≥1 treatment dose and had a baseline assessment. Safety data were assessed using the safety analysis set, defined as patients exposed to ≥1 treatment dose. The primary endpoint (change in body weight) was analyzed using a mixed model for repeated measurements (MMRM), which included group, time, and the corresponding interactions as fixed effects, and baseline weight and sex as covariates. MMRM was used to analyze BMI, WC, VFA, HbA1c, FPG, C-peptide, HOMA-B, HOMA-S, TC, TG, LDL-C, HDL-C, SBP, DBP, ALT, AST, and pulse rate. Categorical variables were evaluated using the χ² test or Fisher exact test. Missing data were imputed using a multiple linear imputation analysis according to the rules of Rubin (Results are shown as adjusted mean and 95% CI, if not indicated otherwise. A | PMC9909427 | |
Results | INSULIN SENSITIVITY | Between March 2022 and June 2022, 212 patients were screened, of which 156 were enrolled and randomized to receive PEG-Loxe (n = 104) or metformin (n = 52). Twelve (11.5%) patients in the PEG-Loxe group and five (9.6%) patients in the metformin group withdrew from the study. The main reasons for withdrawal were AEs and failure to follow-up (Consort flow diagram.The baseline characteristics of the patients are presented in Baseline characteristics of patients.BMI, body mass index; WC, waist circumference; VFA, visceral fat area; HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; HOMA2-%B, updated homeostatic model assessment for beta cell function; HOMA2-%S, updated homeostatic model assessment for insulin sensitivity; TC, total cholesterol; TG, triglycerides; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; SBP, systolic blood pressure; DBP, diastolic blood pressure; AST, aspartate aminotransferase; ALT, alanine aminotransferase; bpm, beats per minute; OAD, oral antidiabetic drug; IQR, interquartile range. Data are expressed as mean (SD), unless otherwise indicated. | PMC9909427 | |
Body weight | weight loss | SECONDARY, INSULIN SENSITIVITY | PEG-Loxe treatment resulted in significant weight loss compared to metformin treatment during the trial period. After 16 weeks, the primary endpoints (least-square mean (LSM) weight loss) were 7.52 kg (8.37%) and 2.96 kg (3.00%) for the PEG-Loxe and metformin groups, respectively, with a between-group mean difference of 4.55 kg (95% CI: 3.43, 5.67; Efficacy endpoints during the 16-week treatment period: time course of absolute Primary and secondary endpoints at week 16.BMI, body mass index; WC, waist circumference; VFA, visceral fat area; HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; HOMA2-%B, updated homeostatic model assessment for b-cell function; HOMA2-%S, updated homeostatic model assessment for insulin sensitivity; TC, total cholesterol; TG, triglycerides; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; SBP, systolic blood pressure; DBP, diastolic blood pressure.After 16 weeks, the proportions of patients with a weight loss of ≥5% were 61.5% and 25.0% in the PEG-Loxe and metformin groups ( | PMC9909427 |
BMI, WC, and VFA | The LSM (95% CI) change in BMI from baseline to week 16 was greater in the PEG-Loxe group [-2.55 (-2.74, -2.37) kg/m | PMC9909427 | ||
Glucose control | The LSM changes in HbA1c after week 16 were similar between the two groups (PEG-Loxe, -1.22% [95% CI: -1.38 to -1.06]; metformin, -1.17% [95% CI: -1.39, -0.96]; | PMC9909427 | ||
Lipid profile and blood pressure | TG | TC, TG, and LDL-C levels were improved with PEG-Loxe treatment compared to metformin treatment ( | PMC9909427 | |
Safety evaluation | ADVERSE EVENT | After 16 weeks of treatment, the incidence of AEs was 46.2% (48/104) and 44.2% (23/52) in the PEG-Loxe and metformin groups, respectively (Summary of safety.AE, adverse event; SAE, serious adverse event; SOC, system organ class; PT, preferred term.At week 16, the change in ALT was -6.88 U/L (95% CI: -7.54, -6.22) with PEG-Loxe and -2.33 U/L (95% CI: -3.17, -1.48) with metformin ( | PMC9909427 | |
Discussion | obesity, obese, overweight, T2DM, weight loss | OBESITY, OBESE, CARDIOVASCULAR DISEASE, HYPERTENSION, DYSLIPIDEMIA | This is the first trial specifically designed to examine the efficacy of PEG-Loxe for weight management and the first trial to investigate PEG-Loxe at a higher dose of 0.3 mg with a fixed-dose-escalation regimen in patients with T2DM. A few studies have reported that a weight-maintenance phase occurred after approximately 12–16 weeks of GLP-1RA treatment (In previous phase 1–3 clinical trials, which enrolled patients with BMIs of 25–27 kg/mWhether directly or indirectly, obesity contributes to the development of several cardiovascular risk factors and comorbidities, including dyslipidemia, hypertension, and cardiovascular disease (The glycemic control effects of 0.1 mg and 0.2 mg PEG-Loxe have been well established in patients with T2DM, as shown by HbA1c reduction ranging from 1.02–1.36% following 12 or 24 weeks of treatment (The safety profile of PEG-Loxe in the present trial was consistent with that in previous trials (This study had several limitations. The open-label design of the present trial may have increased the risk of bias. Furthermore, the clinical trial duration was relatively short, and the full potential of 0.3 mg PEG-Loxe efficacy on weight loss may have been missed. Therefore, additional trials are warranted to assess whether these effects are maintained with long-term 0.3 mg PEG-Loxe treatment.In conclusion, once-weekly subcutaneous PEG-Loxe administration resulted in significantly greater weight loss at 16 weeks, when compared with metformin administration, in overweight or obese patients with T2DM, with lifestyle interventions or OAD therapy. The effects of PEG-Loxe on body weight may provide a treatment option for overweight or obese patients with T2DM. | PMC9909427 |
Data availability statement | The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. | PMC9909427 | ||
Ethics statement | The studies involving human participants were reviewed and approved by the Ethics Committee of Shandong Provincial Hospital. The patients/participants provided their written informed consent to participate in this study. | PMC9909427 | ||
Author contributions | YD and XZ designed the trial. HC, QC, and XZ conducted the trial. HC and QC collected the data. XZ interpreted the data. YZ performed data analysis. HC, QC, and YD drafted the manuscript. XZ reviewed the manuscript. All authors approved the final version of the manuscript. | PMC9909427 | ||
Acknowledgments | The authors gratefully acknowledge the patients who took part in this trial. | PMC9909427 | ||
Conflict of interest | Authors YD and YZ are employed in Hansoh Pharma.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC9909427 | ||
Publisher’s note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. | PMC9909427 | ||
Supplementary material | The Supplementary Material for this article can be found online at: Click here for additional data file. | PMC9909427 | ||
References | PMC9909427 | |||
Key Points | PMC10257092 | |||
Question | depression | What percentage of patients with severe depression experience improvement with antidepressant therapy and by how much? | PMC10257092 | |
Findings | depressive disorder, depression | SECONDARY | In this pooled secondary analysis of data from the US Food and Drug Administration that included 57 313 participants with severe depression from 232 randomized clinical trials of antidepressants for major depressive disorder, all quantiles of depression response were more favorable among drug-assigned participants, by 3% to 14%. These findings depend heavily on statistical assumptions. | PMC10257092 |
Meaning | depression | These findings suggest that antidepressants may improve depression severity for a broad range of patients with severe depression, but for many patients, the magnitude of the reduction may be small. | PMC10257092 | |
Importance | depressive disorder, MDD, disability, depressive symptoms | Major depressive disorder (MDD) is a leading cause of global distress and disability. Earlier studies have indicated that antidepressant therapy confers a modest reduction in depressive symptoms on average, but the distribution of this reduction requires more research. | PMC10257092 | |
Objective | depression | To estimate the distribution of antidepressant response by depression severity. | PMC10257092 | |
Design, Setting, and Participants | MDD, Depression, QTE | SECONDARY | In this secondary analysis of pooled trial data, quantile treatment effect (QTE) analysis was conducted from the US Food and Drug Administration (FDA) database of antidepressant monotherapy for patients with MDD, encompassing 232 positive and negative trials submitted to the FDA between 1979 and 2016. Analysis was restricted to participants with severe MDD (17-item Hamilton Rating Scale for Depression [HAMD-17] score ≥20). Data analysis was conducted from August 16, 2022, to April 16, 2023. | PMC10257092 |
Intervention | Antidepressant monotherapy compared with placebo. | PMC10257092 | ||
Main Outcomes and Measures | depression, Depression | The distribution of percentage depression response was compared between the pooled treatment arm and pooled placebo arm. Percentage depression response was defined as 1 minus the ratio of final depression severity to baseline depression severity, expressed as a percentage. Depression severity was reported in HAMD-17-equivalent units. | PMC10257092 | |
Results | depression | A total of 57 313 participants with severe depression were included in the analysis. There was no significant imbalance in baseline depression severity between the pooled treatment arm and pooled placebo arm, with a mean HAMD-17 difference of 0.037 points ( | PMC10257092 | |
Conclusions and Relevance | depressive disorder, depression, QTE | SECONDARY | In this QTE analysis of pooled clinical trial data from the FDA, antidepressants were found to confer a small reduction in depression severity that was broadly distributed across participants with severe depression. Alternatively, if the assumptions behind the QTE analysis are not met, then the data are also compatible with antidepressants eliciting more complete response in a smaller subset of participants than is suggested by this QTE analysis.This secondary analysis of pooled trial data evaluates the differences among randomized clinical trials in the outcomes of antidepressant monotherapy in patients with major depressive disorder. | PMC10257092 |
Introduction | QTE, depressive disorder, MDD, depression, disability | Major depressive disorder (MDD) is a leading cause of global distress and disability.This debate also depends on how antidepressant efficacy is distributed in populations and in individuals, which is less commonly studied. Both population-level distributions and individual-level distributions matter, and the conceptual differences between them are subtle but important as explained in the eAppendix in Stone et alWe model the distribution of antidepressant response using a quantile treatment effect (QTE) framework.Rank similarity is appropriate when the features that affect a participant’s rank within one treatment arm exert a similar effect in both arms. This is clinically plausible in the depression context because many of the same factors are highly clinically significant in determining the course of a patient’s depression in either arm of a trial. For instance, patients with worsening social circumstances tend to have worse depression responses compared with their same-arm peers in the trial whether assigned to drug or placebo. Similarly, patients whose depression before the trial had been long-standing tend to have worse depression responses compared with their same-arm peers whether assigned to drug or placebo. Rank similarity would be violated if factors that affect antidepressant responsiveness were more important for determining relative rank within an arm than features that affect the course of depression regardless of treatment assignment. A recent review stated that such factors have not been conclusively identified, | PMC10257092 |
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