Analytic Framework (Figure A): To the left of center in the figure, a box represents the populations that are the focus of the evidence gaps. These are children and young adults ages 24 years or younger with a diagnosis of any of the included disorders. Included disorders are: pervasive developmental disorder (PDD), attention deficit hyperactivity disorder (ADHD), disruptive behavior disorder (DBD), bipolar disorder (BPD), schizophrenia/schizophrenia-related psychosis (Sz), tic disorders (Tourette syndrome) (TS), obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), eating disorders (anorexia nervosa, bulimia nervosa, eating disorder not otherwise specified) (AN), or nondisorder-specific severe behavioral issues (e.g., aggression) (BS). Below this box, KQ 1 and KQ 4 are specifically noted in parentheses because they refer to targeted populations of either people with a single diagnosis or clinical or demographic subsets of patients with any of the disorders. Dashed lines with arrows pointing toward the box connect this box to two circles located to the right and above the box. The borders of the circles are dashed lines. The text within the circles describes population characteristics that might influence responses to treatment and methods needed to assess prevalence and treatment outcomes. In the first circle, the text reads “Patient selection criteria that matches typical practice.” In the second circle, the text is “Sociodemographic characteristics: sex, race/ethnicity, cotreatment, history of psychosis, duration of illness.” A thick solid line with an arrow leads to the right from the box representing the populations. This line represents the interventions of interest for the evidence gaps. The interventions are listed under the line. These are: first and second generation antipsychotics. Below the line, KQ 2, KQ 3, and KQ 4 are noted in parentheses to indicate the association between these key questions and the interventions and outcomes of interest. Below the list of interventions is a circle with a dashed line border enclosing the phrase “Dosage variations.” A dashed line with an arrow leads from the circle to the phrase “first and second generation antipsychotics.” A curved solid line with an arrow leads down and to the left from the interventions line. The curved line leads to a oval with a solid line border. The adverse effects that could result from some of the interventions are listed inside this oval. The adverse effects are categorized into major and general. The major adverse effects are mortality, cerebrovascular disease- related events, development of diabetes mellitus, diabetic ketoacidosis, neuroleptic malignant syndrome, seizures, extrapyramidal effects, cardiomyopathies, cardiac arrhythmias, agranulocytosis. The general adverse events are weight gain, agitation, constipation, sedation, elevated cholesterol, elevated transaminases, adverse events related to prolactin elevations, galactorrhea, exercise intolerance, precocious puberty. Outside the border and just above the circle, the term “KQ 2” is noted in parentheses to show the association between key question 2 and the potential adverse effects. To the right of the adverse effects circle are two circles each with dashed line borders and dashed lines with arrows leading from them to the adverse effects oval. The text within the first circle reads “Standardized pediatric side-effect scales.” The text in the second circle reads “Direct and indirect comparison of adverse effects.” The thick solid line leading from the population box on the left, ends at two large boxes on the right side of the figure. These boxes contain lists, respectively, of the intermediate and long-term health outcomes of interest. The intermediate outcomes are listed in the first box. These are core illness symptom response rates with corresponding dose and duration of response, acute school performance/attendance, and acute legal/justice system interaction (i.e., arrests, detention). The long-term outcomes are listed in the second box. These are: long-term symptom response rates with corresponding dose, duration of response, remission, relapse, speed of response, time of discontinuation of medication; growth and maturation; cognitive and emotional development; suicide-related behaviors, death by suicide; medication adherence and persistence; school performance/attendance; work-related functional capacity; patient insight into illness; patient/care provider-reporter outcomes (e.g., levels of physical activity/inactivity, diet, food preferences); health-related quality of life (HRQoL); legal/justice system interaction; health care system utilization; direct or indirect impacts from medication use (e.g., development of diabetes mellitus, weight gain, delayed sexual maturation/fertility, bone density, cardiovascular effects, life expectancy, metabolic effects). Located above these boxes are three circles with dashed line borders. Dashed lines with arrows lead from the circles to one or both boxes. The text within the first circle on the left reads “Consensus on clinically meaningful differences.” The dashed lines lead from this circle to both boxes listing the intermediate and long-term outcomes. The text in the middle circle with the dashed border reads “Adequate blinding of study participants, concealment of treatment allocation, handling of missing data.” One dashed line leads from this circle to the long-term outcomes box. The text in the third circle on the right reads “Standardized and comparable measurement for outcomes.” One dashed line leads from this circle to the long-term outcomes box.

Figure AAnalytic framework depicting relationships between key questions, populations, interventions, outcomes, and components of evidence gaps

From: Executive Summary

Cover of Future Research Needs for First- and Second-Generation Antipsychotics for Children and Young Adults
Future Research Needs for First- and Second-Generation Antipsychotics for Children and Young Adults [Internet].
Future Research Needs Papers, No. 13.
Christian R, Saavedra L, Gaynes BN, et al.

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