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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....
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]...
PMC9986654
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 representativ...
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 C...
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...
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 ...
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 secon...
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 intentio...
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...
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 intervent...
PMC9986654
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...
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 techni...
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; prep...
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 ...
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 Interac...
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 mon...
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 diagno...
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...
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. The...
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 increa...
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 suitabl...
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 co...
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...
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 wi...
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)....
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 iBASI...
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 c...
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 in...
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 saving...
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 sub...
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...
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 thiazolidine...
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...
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.M...
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 d...
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), triglyceride...
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 ...
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...
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 o...
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 ...
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 approximat...
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 ...
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 ...
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 rest...
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-eq...
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...
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...
PMC10257092