Advancing implementation science through measure development and evaluation: a study protocol.

BACKGROUND: Significant gaps related to measurement issues are among the most critical barriers to advancing implementation science. Three issues motivated the study aims: (a) the lack of stakeholder involvement in defining pragmatic measure qualities; (b) the dearth of measures, particularly for implementation outcomes; and (c) unknown psychometric and pragmatic strength of existing measures. Aim 1: Establish a stakeholder-driven operationalization of pragmatic measures and develop reliable, valid rating criteria for assessing the construct. Aim 2: Develop reliable, valid, and pragmatic measures of three critical implementation outcomes, acceptability, appropriateness, and feasibility. Aim 3: Identify Consolidated Framework for Implementation Research and Implementation Outcome Framework-linked measures that demonstrate both psychometric and pragmatic strength. METHODS/DESIGN: For Aim 1, we will conduct (a) interviews with stakeholder panelists (N = 7) and complete a literature review to populate pragmatic measure construct criteria, (b) Q-sort activities (N = 20) to clarify the internal structure of the definition, (c) Delphi activities (N = 20) to achieve consensus on the dimension priorities, (d) test-retest and inter-rater reliability assessments of the emergent rating system, and (e) known-groups validity testing of the top three prioritized pragmatic criteria. For Aim 2, our systematic development process involves domain delineation, item generation, substantive validity assessment, structural validity assessment, reliability assessment, and predictive validity assessment. We will also assess discriminant validity, known-groups validity, structural invariance, sensitivity to change, and other pragmatic features. For Aim 3, we will refine our established evidence-based assessment (EBA) criteria, extract the relevant data from the literature, rate each measure using the EBA criteria, and summarize the data. DISCUSSION: The study outputs of each aim are expected to have a positive impact as they will establish and guide a comprehensive measurement-focused research agenda for implementation science and provide empirically supported measures, tools, and methods for accomplishing this work.

In vitro models to evaluate the permeability of poorly soluble drug entities: challenges and perspectives.

The application of in vitro models in drug permeability studies represents a useful screening tool for assessing the biopharmaceutical appropriateness of new chemical entities (NCEs). Of note, there remains an ever-increasing number of NCEs which exhibit poor aqueous solubility. However, in their classical configuration, both cellular and non-cellular in vitro models show numerous deficiencies in their ability to accurately model the absorption of such compounds. As a consequence, investigators continue to explore the possibility of modifying different experimental parameters in an attempt to yield a more bio-relevant model system which offers good compatibility with poorly soluble compounds. Moreover, in many instances poorly soluble drugs necessitate the inclusion of excipients to facilitate efficient delivery and to enhance their bioavailability. Thus, there exists an increasing demand for in vitro models which can effectively appraise the effects of excipients on a drug's permeability. Herein, we provide an overview of those models currently in use and discuss their associated benefits and drawbacks. Furthermore, we review the challenges encountered in assaying the permeability of poorly soluble drugs and critically assess those experimental modifications and solutions employed thus far in terms of their capacity to generate results with improved accuracy and precision.

Response of feral cats to vaccination at the time of neutering.

OBJECTIVE: To determine whether administration of inactivated virus or modified-live virus (MLV) vaccines to feral cats at the time of neutering induces protective serum antiviral antibody titers. DESIGN: Prospective study. ANIMALS: 61 feral cats included in a trap-neuter-return program in Florida. PROCEDURES: Each cat received vaccines against feline panleukopenia virus (FPV), feline herpes virus (FHV), feline calicivirus (FCV), FeLV, and rabies virus (RV). Immediately on completion of surgery, vaccines that contained inactivated RV and FeLV antigens and either MLV or inactivated FPV, FHV, and FCV antigens were administered. Titers of antiviral antibodies (except those against FeLV) were assessed in serum samples obtained immediately prior to surgery and approximately 10 weeks later. RESULTS: Prior to vaccination, some of the cats had protective serum antibody titers against FPV (33%), FHV (21%), FCV (64%), and RV (3%). Following vaccination, the overall proportion of cats with protective serum antiviral antibody titers increased (FPV [90%], FHV [56%], FCV [93%], and RV [98%]). With the exception of the FHV vaccine, there were no differences in the proportions of cats protected with inactivated virus versus MLV vaccines. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that exposure to FPV, FHV, and FCV is common among feral cats and that a high proportion of cats are susceptible to RV infection. Feral cats appeared to have an excellent immune response following vaccination at the time of neutering. Incorporation of vaccination into trap-neuter-return programs is likely to protect the health of individual cats and possibly reduce the disease burden in the community.