2023 White Paper on Recent Issues in Bioanalysis: ISR for ADA Assays, the Rise of dPCR vs qPCR, International Reference Standards for Vaccine Assays, Anti-AAV TAb Post-Dose Assessment, NanoString Validation, ELISpot as Gold Standard (Part 3 - Recommendations on Gene Therapy, Cell Therapy, Vaccines Immunogenicity & Technologies; Biotherapeutics Immunogenicity & Risk Assessment; ADA/NAb Assay/Reporting Harmonization).

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) are published in volume 16 of Bioanalysis, issues 8 and 9 (2024), respectively.

Risk-based approach of bioanalytical methods for clinical immunogenicity assessment of multidomain biotherapeutics.

Tweetable abstract Risk-based bioanalytical method development for clinical antidrug antibody detection and characterization of multidomain biotherapeutics.

2022 White Paper on Recent Issues in Bioanalysis: FDA Draft Guidance on Immunogenicity Information in Prescription Drug Labeling, LNP & Viral Vectors Therapeutics/Vaccines Immunogenicity, Prolongation Effect, ADA Affinity, Risk-based Approaches, NGS, qPCR, ddPCR Assays (Part 3 - Recommendations on Gene Therapy, Cell Therapy, Vaccines Immunogenicity & Technologies; Immunogenicity & Risk Assessment of Biotherapeutics and Novel Modalities; NAb Assays Integrated Approach).

The 2022 16th Workshop on Recent Issues in Bioanalysis (WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1 (Mass Spectrometry and ICH M10) and Part 2 (LBA, Biomarkers/CDx and Cytometry) are published in volume 15 of Bioanalysis, issues 16 and 15 (2023), respectively.

When Adverse Childhood Experiences Present to a Statewide Child Psychiatry Access Program.

Many children experience adversity, yet few receive needed psychiatric services. Pediatric primary care providers (PCPs) are uniquely positioned to intervene but often lack training and resources to provide patients with adverse childhood experiences (ACEs) the psychiatric support they need. The current study examines characteristics of youth with and without ACEs who were the focus of PCP contacts with a statewide child psychiatry access program (CPAP). Compared to those without ACEs, patients with ACEs were more often receiving medication treatment at time of CPAP contact, prescribed two or more psychotropic medications, and diagnosed with two or more mental health disorders. Study findings indicate that patients with ACEs for whom PCPs sought CPAP support were experiencing more clinically severe and complex mental health concerns. These findings underscore the important role of CPAPs in supporting PCPs with pediatric patients who have ACEs and will inform training provided by CPAPs to PCPs.

Characteristics of Patients Served by a Statewide Child Psychiatry Access Program.

OBJECTIVE: Maryland's Behavioral Health Integration in Pediatric Primary Care (BHIPP) is a child psychiatry access program offering child-adolescent psychiatry consultation, resource and referral networking, and direct-to-patient mental health intervention. This study investigated characteristics of patients for whom primary care providers sought BHIPP services. METHODS: Data from 6,939 unique patient contacts between October 2012 and March 2020 were collected on service type, demographic characteristics, presenting concerns, clinical severity, clinicians' diagnostic impressions, current treatments, and BHIPP recommendations. Descriptive statistics and latent class analysis were used. RESULTS: Of the 6,939 patient contacts, 38.6% were for direct-to-patient mental health intervention, 27.3% for child-adolescent psychiatry consultation, and 34.2% for resource and referral networking. In total, 50.3% of patients were female, 58.7% were White, and 32.7% were already receiving mental health services. Latent class analysis identified four classes of presenting concerns: anxiety only (44.2%); behavior problems only (30.7%); mood and anxiety (17.1%); and attention, behavior, and learning problems (8.0%). Compared with patients in the anxiety-only class, those in the attention, behavior, and learning problems class were more likely to receive direct-to-patient mental health intervention (OR=3.59), and BHIPP clinicians were more likely to recommend in-office behavioral interventions for those in the mood and anxiety class (OR=1.62) and behavior problems-only class (OR=1.55). CONCLUSIONS: Patients supported through BHIPP varied in presenting concerns, condition severity and complexity, current receipt of services, and BHIPP utilization. Latent class analysis yielded more clinically useful information about the nature and complexity of patients' concerns than did consideration of individual presenting concerns.

Anti-drug Antibody Sample Testing and Reporting Harmonization.

A clear scientific and operational need exists for harmonized bioanalytical immunogenicity study reporting to facilitate communication of immunogenicity findings and expedient review by industry and health authorities. To address these key bioanalytical reporting gaps and provide a report structure for documenting immunogenicity results, this cross-industry group was formed to establish harmonized recommendations and a develop a submission template to facilitate agency filings. Provided here are recommendations for reporting clinical anti-drug antibody (ADA) assay results using ligand-binding assay technologies. This publication describes the essential bioanalytical report (BAR) elements such as the method, critical reagents and equipment, study samples, results, and data analysis, and provides a template for a suggested structure for the ADA BAR. This publication focuses on the content and presentation of the bioanalytical ADA sample analysis report. The interpretation of immunogenicity data, including the evaluation of the impact of ADA on safety, exposure, and efficacy, is out of scope of this publication.

Characteristics of Primary Care Providers' Consultations With a Statewide Child Psychiatry Access Program Regarding Autism Spectrum Disorder.

BACKGROUND: Child Psychiatry Access Programs (CPAPs) provide consultative support for pediatric primary care providers (PCPs) to treat co-morbid mental health (MH) symptoms among patients with Autism Spectrum Disorder (ASD). OBJECTIVES: We examined differences in illness severity, comorbidity, and psychotropic medication use between patients with and without ASD for whom primary care providers sought consultation from Maryland's CPAP. METHODS: We examined N = 3641 Maryland's CPAP consultations from 2012 to 2019; n = 311 were consultations for ASD. Demographics, treatment recommendations, diagnoses, and Clinical Global Impression-Severity scores were collected. Patients who received psychotropic medication or psychotherapy by any mental health provider were defined as comanaged. Descriptive statistics and logistic regression were conducted. Sample size for regression was N = 1854. RESULTS: Compared with non-ASD, patients with consults for ASD were more often male (P < 0.001), aged 0-5 years (P < 0.001), severely ill (Clinical Global Impression-Severity > 4) (P < 0.001), and prescribed stimulants, nonstimulant attention-deficit hyperactivity disorder medications, and antipsychotic medications (P < 0.001). Controlling for key covariates, consultations for youth displaying aggression were 3.02 times (P < 0.001) more likely, with Clinical Global Impression-Severity > 4 were 2.36 times (P < 0.001) more likely, and prescribed antipsychotics were 4.30 times more likely to concern an ASD patient (P < 0.001). A larger proportion of ASD patients (vs. non-ASD) had comorbid psychiatric diagnoses of attention-deficit hyperactivity disorder, a learning disability, and disruptive behavior disorder vs. a smaller proportion with major depressive disorder. CONCLUSIONS: ASD patients for whom primary care providers sought Maryland's CPAP consultation were more severe and complex than non-ASD patients in terms of comorbid diagnoses and medication regimen.

Trends in Mental Health Concerns Reported to Two Pediatric Mental Health Care Access Programs During the COVID-19 Pandemic.

OBJECTIVE: Pediatric Mental Health Care Access (PMHCA) programs increase access to mental health care by providing training, consultation, and resource-referral support to primary care providers (PCPs). The authors compared trends in services provided by two PMHCA programs during the COVID-19 pandemic. METHODS: Maryland and Mississippi PMHCA programs had 2,840 contacts with PCPs from January 2019 to March 2021. Descriptive trends on PMHCA program utilization, service type, clinical severity, diagnostic complexity, and PCP contact reasons were reported. RESULTS: Both programs observed significant increases in call volume during the COVID-19 pandemic compared with before COVID-19. Increases were observed in calls regarding patients with multiple diagnoses (Maryland, 20% to 37%; Mississippi, 0% to 11%) as well as patients with mood and anxiety symptoms. CONCLUSIONS: Changes in PMHCA program usage suggest that PCPs identified more complex mental health concerns, particularly regarding mood and anxiety, during the pandemic than before COVID-19. Trends underscore the importance of PMHCA programs in supporting PCPs with managing pediatric mental health concerns.

Buprenorphine Induction in a Rural Maryland Detention Center During COVID-19: Implementation and Preliminary Outcomes of a Novel Telemedicine Treatment Program for Incarcerated Individuals With Opioid Use Disorder.

Over 10 million individuals pass through U.S. detention centers on an annual basis, with nearly two-thirds meeting criteria for drug dependence/abuse. Despite proven efficacy, treatment with medications for opioid use disorder (MOUD) is underutilized in jail settings-a gap that could be addressed using telemedicine. Here we describe a new program of telemedicine-based clinical provision of new/continuing buprenorphine treatment for individuals detained in a rural jail. Implementation objectives were completed between January and August 2020, and patient encounters were conducted between August 2020 and February 2021. We established (i) telemedicine hardware/software capability; (ii) a screening process; (iii) buprenorphine administration methods; (iv) necessary medical release procedures; (v) telemedicine encounter coordination and medication prescription procedures; and (vi) a research platform. Seven incarcerated patients have been treated, two of whom were referred from community treatment. Patients were mostly male (71%), non-Hispanic White (86%), and averaged 33 years old. All patients tested positive for an opioid upon intake and began/continued buprenorphine treatment in the jail. Average time to first MOUD appointment was 9 days and patients were maintained in treatment an average 21 days. Referrals for continuing community treatment were offered to all patients prior to discharge. We report successful implementation of telemedicine MOUD in a rural detention center, with treatment engagement and initiation occurring prior to the high-risk period of discharge. The fact that this program was launched during the height of the pandemic highlights the flexibility of telemedicine-based buprenorphine treatment. Challenges and obstacles to implementation of buprenorphine treatment in a correctional system are discussed.

Mobile Telemedicine for Buprenorphine Treatment in Rural Populations With Opioid Use Disorder.

Importance: The demand for medications for opioid use disorder (MOUD) in rural US counties far outweighs their availability. Novel approaches to extend treatment capacity include telemedicine (TM) and mobile treatment on demand; however, their combined use has not been reported or evaluated. Objective: To evaluate the use of a TM mobile treatment unit (TM-MTU) to improve access to MOUD for individuals living in an underserved rural area. Design, Setting, and Participants: This quality improvement study evaluated data collected from adult outpatients with a diagnosis of OUD enrolled in the TM-MTU initiative from February 2019 (program inception) to June 2020. Program staff traveled to rural areas in a modified recreational vehicle equipped with medical, videoconferencing, and data collection devices. Patients were virtually connected with physicians based more than 70 miles (112 km) away. Data analysis was performed from June to October 2020. Intervention: Patients received buprenorphine prescriptions after initial teleconsultation and follow-up visits from a study physician specialized in addiction psychiatry and medicine. Main Outcomes and Measures: The primary outcome was 3-month treatment retention, and the secondary outcome was opioid-positive urine screens. Exploratory outcomes included use of other drugs and patients' travel distance to treatment. Results: A total of 118 patients were enrolled in treatment, of whom 94 were seen for follow-up treatment predominantly (at least 2 of 3 visits [>50%]) on the TM-MTU; only those 94 patients' data are considered in all analyses. The mean (SD) age of patients was 36.53 (9.78) years, 59 (62.77%) were men, 71 (75.53%) identified as White, and 90 (95.74%) were of non-Hispanic ethnicity. Fifty-five patients (58.51%) were retained in treatment by 3 months (90 days) after baseline. Opioid use was reduced by 32.84% at 3 months, compared with baseline, and was negatively associated with treatment duration (F = 12.69; P = .001). In addition, compared with the nearest brick-and-mortar treatment location, TM-MTU treatment was a mean of 6.52 miles (range, 0.10-58.70 miles) (10.43 km; range, 0.16-93.92 km) and a mean of 10 minutes (range, 1-49 minutes) closer for patients. Conclusions and Relevance: These data demonstrate the feasibility of combining TM with mobile treatment, with outcomes (retention and opioid use) similar to those obtained from office-based TM MOUD programs. By implementing a traveling virtual platform, this clinical paradigm not only helps fill the void of rural MOUD practitioners but also facilitates access to underserved populations who are less likely to reach traditional medical settings, with critical relevance in the context of the COVID-19 pandemic.

Using multiple platforms for critical reagents selection process to support pharmacokinetic ligand-binding assay development.

We have evaluated the utility of epitope binning on biolayer interferometry (BLI) as a strategy to funnel the selection of candidate pairs suitable for pharmacokinetic assay development. Totally, 8 anti-Idiotypic monoclonal antibodies in 64 possible combinations were tested by BLI, ELISA and Gyrolab®. Two epitope binning approaches were utilized, in-tandem and classic sandwich. Both formats identified four mutually exclusive bins providing 31 and 25 possible antibody pair combinations, respectively. In contrast, the ELISA and Gyrolab yielded 18 and 9 positive pairs, respectively, with only a partial correlation to the BLI results. Several positive pairs by ELISA and Gyrolab, screened negative by BLI. Just over half of the pairs predicted by BLI were positive on ELISA and less than a quarter were positive on Gyrolab. This evaluation showed, in our case, that BLI was limited in its ability to predict candidate pairs that would be successful in pharmacokinetic method development.

Pediatric Primary Care Provider Comfort with Mental Health Practices: A Needs Assessment of Regions with Shortages of Treatment Access.

OBJECTIVES: Nearly 50% of children with a mental health concern do not receive treatment. Child Psychiatry Access Programs like Behavioral Health Integration in Pediatric Primary Care (BHIPP) address regional shortages of mental health treatment access by providing training and consultation to primary care providers (PCPs) in managing mental health concerns. This study assessed PCPs' comfort with mental health practices to inform expansion of BHIPP services. METHODS: Pediatric PCPs in 114 practices in three rural regions of Maryland were recruited to participate in a survey about their comfort with mental health practices and access to mental health providers for referral. Descriptives, Friedman's test, and post hoc pairwise comparisons were used to examine survey responses. RESULTS: Participants were 107 PCPs. Most respondents were physicians (53.3%) or nurse practitioners/physician's assistants (39.3%). Friedman's test, χ2(7)= 210.15, p<.001, revealed significant within and between-group differences in PCP comfort with mental health practices. Post hoc pairwise comparisons indicated greater comfort providing mental health screening and referrals compared to prescribing psychiatric medications, providing psychoeducation or in-office mental health interventions. A Wilcoxon-signed rank test showed significantly more respondents agreed they could find a therapist than a psychiatrist in a timely manner, Z= -5.93, p<.001. CONCLUSIONS: Pediatric PCPs were more comfortable with providing mental health assessment and referrals than treatment. However, PCPs reported difficulty finding therapists and psychiatrists for their patients. Findings underscore the need for longitudinal training to increase PCP comfort with mental health treatment. Additionally, strategies such as telepsychiatry are needed to address the disproportionate need for child psychiatrists.

Program development and implementation outcomes of a statewide addiction consultation service: Maryland Addiction Consultation Service (MACS).

Background: As the opioid epidemic continues, there is a mounting sense of urgency to improve access to high-quality early identification and treatment services. However, the need is outpacing capacity in many states and effective solutions to support primary care and specialty prescribers to identify and treat more patients with opioid use disorders are still emerging. This paper describes one state's approach to increase access to medication for opioid use disorders (MOUD) through development and implementation of a statewide addiction consultation service: Maryland Addiction Consultation Service (MACS). Methods: Program components include a warmline, outreach and training, and resource and referral linkages for prescribers based on related consultation service models and documented barriers to prescribing MOUDs. Results: Initial implementation outcomes indicate service components are being adopted as intended and by the target audience; many prescribers who engaged with the service have their buprenorphine waiver (44%) but do not have any additional formal addiction training (57%). Also, statewide penetration is promising with prescriber engagement in 100% of counites, however only 33% of counties in engaged in all four types of MACS services. Most calls (61%) originated from urban counties. Conclusions: The MACS program increases access to specialty addiction medicine consultation and training through use of technology. MACS can serve as a model for other states looking to bridge the gap in access to addiction treatment.

Pharmacokinetics of idarucizumab and its target dabigatran in patients requiring urgent reversal of the anticoagulant effect of dabigatran.

BACKGROUND: Idarucizumab is a monoclonal antibody fragment that reverses dabigatran anticoagulation. Pharmacokinetics (PK) of idarucizumab have been described in healthy, elderly, or renally impaired (RI) volunteers, but PK data in patients are lacking. OBJECTIVES: This analysis describes the PK of idarucizumab and its target dabigatran in bleeding/surgical patients. PATIENTS AND METHODS: Results from the Reversal Effects of Idarucizumab on Active Dabigatran study, a prospective, multicenter, single-arm study demonstrated the reversal of dabigatran anticoagulation by idarucizumab in patients with uncontrollable bleeding (group A) or who needed urgent surgery (group B). Idarucizumab and unbound dabigatran concentrations, immunogenicity, and pharmacodynamics were assessed. RESULTS: Total and unbound dabigatran levels at baseline were 165 ng/mL vs 110 ng/mL and 103 ng/mL vs 69.5 ng/mL in group A and B patients, respectively. Maximum plasma concentrations and area under the curves (AUC0-24 ) of idarucizumab in group A vs B, respectively, were 24 900 nmol/L vs 25 000 nmol/L and 76 600 nmol/h/L vs 68 000 nmol/h/L. Idarucizumab AUC0-24 increased by 38% in mild, 90% in moderate, and 146% in severe RI patients vs normal renal function. Hepatic impairment or geographical region had no relevant effect on idarucizumab PK. Idarucizumab immediately decreased unbound dabigatran concentration (<20 ng/mL). A linear correlation was observed between unbound dabigatran and diluted thrombin time and ecarin clotting time. Antidrug antibody titers were low (1-64 at day 30; 0-16 at day 90) and had no impact on idarucizumab PK and pharmacodynamics. CONCLUSION: Idarucizumab PK in target patients was consistent with phase I data. Patient characteristics had no impact on PK, whereas RI increased the exposure of idarucizumab and dabigatran. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02104947.

Retrospective analysis of model-based predictivity of human pharmacokinetics for anti-IL-36R monoclonal antibody MAB92 using a rat anti-mouse IL-36R monoclonal antibody and RNA expression data (FANTOM5).

Accurate prediction of the human pharmacokinetics (PK) of a candidate monoclonal antibody from nonclinical data is critical to maximize the success of clinical trials. However, for monoclonal antibodies exhibiting nonlinear clearance due to target-mediated drug disposition, PK predictions are particularly challenging. That challenge is further compounded for molecules lacking cross-reactivity in a nonhuman primate, in which case a surrogate antibody selective for the target in rodent may be required. For these cases, prediction of human PK must account for any interspecies differences in binding kinetics, target expression, target turnover, and potentially epitope. We present here a model-based method for predicting the human PK of MAB92 (also known as BI 655130), a humanized IgG1 κ monoclonal antibody directed against human IL-36R. Preclinical PK was generated in the mouse with a chimeric rat anti-mouse IgG2a surrogate antibody cross-reactive against mouse IL-36R. Target-specific parameters such as antibody binding affinity (KD), internalization rate of the drug target complex (kint), target degradation rate (kdeg), and target abundance (R0) were integrated into the model. Two different methods of assigning human R0 were evaluated: the first assumed comparable expression between human and mouse and the second used high-resolution mRNA transcriptome data (FANTOM5) as a surrogate for expression. Utilizing the mouse R0 to predict human PK, AUC0-∞ was substantially underpredicted for nonsaturating doses; however, after correcting for differences in RNA transcriptome between species, AUC0-∞ was predicted largely within 1.5-fold of observations in first-in-human studies, demonstrating the validity of the modeling approach. Our results suggest that semi-mechanistic models incorporating RNA transcriptome data and target-specific parameters may improve the predictivity of first-in-human PK.

When Behavioral Health Concerns Present in Pediatric Primary Care: Factors Influencing Provider Decision-Making.

Primary care providers (PCPs) frequently encounter behavioral health (BH) needs among their pediatric patients. However, PCPs report variable training in and comfort with BH, and questions remain about how and when PCPs address pediatric BH needs. Existing literature on PCP decisions to address pediatric BH in-office versus referring to subspecialty BH is limited and findings are mixed. Accordingly, this study sought to examine parameters and contextual factors influencing PCP decisions and practices related to BH care. Qualitative interview results with 21 PCPs in Maryland indicated that decisions about how and when to address pediatric BH concerns are influenced by the type BH service needed, patient characteristics, the availability of BH services in the community, and possibly PCPs' perceptions of BH care as a distinct subspecialty. Findings suggest that efforts to support individual PCPs' capacity to address BH within primary care must be balanced by efforts to expand the subspecialty BH workforce.

Pediatric Primary Care Providers' Use of Behavioral Health Consultation.

This column describes a qualitative study in which 32 primary care providers (PCPs) reported barriers to and facilitators of using a behavioral health (BH) consultation program. Barriers included program incompatibility with organizational culture, limited exposure to the program, existing access to referral sources, and negative beliefs about BH consultation. Reported facilitators included having personal relationships with BH program staff, exposure to program information, and positive beliefs about BH consultation. PCPs recommended outreach activities and optimal program features to increase use of BH consultation.

Dissemination and implementation science in program evaluation: A telemental health clinical consultation case example.

Increased attention has been placed on evaluating the extent to which clinical programs that support the behavioral health needs of youth have effective processes and result in improved patient outcomes. Several theoretical frameworks from dissemination and implementation (D&I) science have been put forth to guide the evaluation of behavioral health program implemented in the context of real-world settings. Although a strong rationale for the integration of D&I science in program evaluation exists, few examples exist available to guide the evaluator in integrating D&I science in the planning and execution of evaluation activities. This paper seeks to inform program evaluation efforts by outlining two D&I frameworks and describing their integration in program evaluation design. Specifically, this paper seeks to support evaluation efforts by illustrating the use of these frameworks via a case example of a telemental health consultation program in pediatric primary care designed to improve access to behavioral health care for children and adolescents in rural settings. Lessons learned from this effort, as well as recommendations regarding the future evaluation of programs using D&I science to support behavioral health care in community-based settings are discussed.

The Five S's: A Communication Tool for Child Psychiatric Access Projects.

Given the gap in child psychiatric services available to meet existing pediatric behavioral health needs, children and families are increasingly seeking behavioral health services from their primary care clinicians (PCCs). However, many pediatricians report not feeling adequately trained to meet these needs. As a result, child psychiatric access projects (CPAPs) are being developed around the country to support the integration of care for children. Despite the promise and success of these programs, there are barriers, including the challenge of effective communication between PCCs and child psychiatrists. Consultants from the Maryland CPAP, the Behavioral Health Integration in Pediatric Primary Care (BHIPP) project, have developed a framework called the Five S's. The Five S's are Safety, Specific Behaviors, Setting, Scary Things, and Screening/Services. It is a tool that can be used to help PCCs and child psychiatrists communicate and collaborate to formulate pediatric behavioral health cases for consultation or referral requests. Each of these components and its importance to the case consultation are described. Two case studies are presented that illustrate how the Five S's tool can be used in clinical consultation between PCC and child psychiatrist. We also describe the utility of the tool beyond its use in behavioral health consultation.