Research Foundations, Methods, and Issues in Developmental-Behavioral Pediatrics

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CHAPTER 3 Research Foundations, Methods, and Issues in Developmental-Behavioral Pediatrics

THE UNIQUE NATURE OF DEVELOPMENTAL-BEHAVIORAL PEDIATRIC RESEARCH

The scope of research in the field of developmental-behavioral pediatrics (DBP) is as diverse and rich as the clinical field itself. A wide range of research methods and analytical techniques accounts for both its depth and its complexity. The same characteristics of research in the field that render the potential for its findings to be of such practical significance and relevance often pose critical challenges to ensuring its scientific validity.

The research and the associated research teams are often multidisciplinary, permitting an application of various methodological approaches. The field of DBP permits integration of complementary theoretical perspectives and methods, such as the blending or juxtaposition of quantitative methods characteristic of medical science with qualitative approaches more typical of social science research. Research training in the field is therefore more eclectic and broader than in subspecialties that rely almost exclusively on basic science techniques. The field does not have one well-circumscribed set of research methods that can be mastered in a relatively short time. For quality research in DBP, multidisciplinary teams must consist of individuals who can each contribute their own perspective and skills, and each team member must be adequately informed of the basic principles inherent in the research approaches of the other disciplines.

DBP research often aims to study the full spectrum of child development and behavior: from normal variations to concerns or problems to clinical disorders. One of the driving forces for establishing the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders was to standardize the diagnostic criteria for disorders to foster consistency in research in mental illness.1 Research that incorporates the continuum of developmental and behavioral difficulties must establish reliable and valid outcome measures for subthreshold or problem conditions or criteria for identifying where on the bell-shape curve of behavior or development is the appropriate cutoff for defining a concern or a problem. Although achieving reliability in delineating the diagnostic criteria for a mental illness may be challenging, it is often even more elusive for a behavioral problem or personality trait. One common approach is to inquire whether the characteristic of interest (e.g., attention) is believed to occur significantly more often in one person than in typical peers of the same age or developmental level and to require an association with some perceived impairment (e.g., attention-deficit/hyperactivity disorder [ADHD]). This approach often introduces a reliance on subjective, self-reported measures of perceived impairment or relative deviation from perceived norms that can compromise validity and produce a reporting bias.

Research in DBP often addresses more abstract issues, such as community support or adjustment to illness. Because much of the research addresses such common topics, the researcher may assume that the methodology is therefore “simple.” But, in fact, operationalizing these variables and developing and validating relevant measures are difficult. Much of the research in DBP involves measuring constructs for which validated measures do not already exist and for which objective, concrete biological outcome measures are not feasible.

Because DBP often assumes an ecological perspective, researchers are more apt to look critically at sociocultural influences on child development and behavior. Such factors are difficult to measure, even harder to report accurately, and far more difficult to interpret or explain. The use of race and ethnicity as explanatory variables illustrate the complexity of this issue.2 Researchers who understand the complexity of social and cultural influences appreciate the futility of controlling for all relevant influences within an ecological model.

Despite these challenges, the complexity of research design issues in DBP fosters its richness. The multiple perspectives and theories and the diversity of available methodological approaches enable the construction of rich, multidimensional theoretical models. Researchers must necessarily explore not only outcome measures but also mediators and moderators (see Chapter 2). The complexity is increased by the factor of time and the challenges inherent in measuring one construct in the context of a child’s developmental trajectory. For example, in studies of the influences of early childhood experiences on later language outcomes, investigators need to consider not only the multiple environmental, familial, cultural, and community factors that may influence language development but also the reality that developmental processes are not static in the individual child. Parsing out how much of change in language development is attributable to the normative process of child development ot to inherent deficits in the child, social, environmental, family or community factors, or the unanticipated effect of uncontrolled historical events (such as changes in preschool policy or educational interventions) can be daunting.

CROSS-CUTTING METHODOLOGICAL AND THEORETICAL ISSUES

The nature of DBP research introduces a range of cross-cutting methodological and theoretical concerns that must be addressed to ensure the validity of the findings. This section highlights select examples that illustrate the complexity of the issues that are involved.

Incorporating Child Development within Child Development Research

Central to any research in the area of child development is an appreciation that children’s capabilities and behavior change over time as a result of developmental processes, independent of other factors or interventions. Measures of skills or capabilities therefore need to be adjusted and compared with norms for different ages/stages, introducing analytical concerns for cross-sectional studies involving children of different ages or developmental stages. Measurements of the effect of interventions provided over time may also be compromised by analytical concerns inherent in measuring the same domain at different developmental stages, which may necessitate the use of different age/stage-appropriate instruments or, at the very least, correction for age/stage. In addition, measurement of children’s abilities may be confounded by the child’s developmental capacity to understand instructions and communicate comprehension. For example, young children have been described as having difficulty appreciating the perspective of someone else. It is possible that such difficulty may result, at least in part, from limitations in their ability to comprehend the task requested, their language ability to communicate their understanding, or the researcher’s ability to communicate the task required. Research on young children’s understanding of the concepts of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) initially suggested that young children’s understanding of core concepts of illness was significantly limited developmentally, which seriously constrained their capacity to benefit from educational interventions; however, subsequent research demonstrated that a developmentally based educational intervention could result in dramatic gains in young children’s conceptual understanding in this area.3 In other words, what appeared at first to be a limitation in children’s ability to learn was subsequently found to represent limitations in adults’ understanding of how to teach effectively and/or in researchers’ ability to measure validly children’s underlying comprehension.

Qualitative Methods

Qualitative research methods are most appropriate in situations in which little is known about a phenomenon or when attempts are being made to generate new theories or revise preexisting theories. Qualitative research is inductive rather than deductive and is used to describe phenomena in detail, without answering questions of causality or demonstrating clear relationships among variables. Researchers in DBP should be familiar with common ethnographic methods, such as participant observation (useful for studying interactions and behavior), ethnographic interviewing (useful for studying personal experiences and perspectives), and focus groups (involving moderated discussion to glean information about a specific area of interest relatively rapidly). In comparison with quantitative research, qualitative methods entail different sampling procedures (e.g., purposive rather than random or consecutive sampling; “snow-balling,” which involves identifying cases with connections to other cases), different sample size requirements (e.g., the researcher may sample and analyze in an iterative manner until data saturation occurs, so that no new themes or hypotheses are generated on subsequent analysis), different data management and analytic techniques (e.g., reduction of data to key themes and ideas, which are then coded and organized into domains that yield tentative impressions and hypotheses, which serve as the basis of the next set of data collection, continuing until data saturation occurs and final concepts are generated), and different conventions for writing up and presenting data and analyses. The strength of the findings is maximized through triangulation of data, investigator (e.g., use of researchers from different disciplines and perspectives or several researchers to independently code the same data), theory (i.e., use of multiple perspectives), or method (e.g., use of focus groups and individual interviews to obtain complementary data).

Intervention Fidelity and Treatment Dose

Interventions are often delivered in naturalistic and group settings by individuals who are not part of the research team, such as teachers, parents, and home visitors. Although this allows for the testing of interventions that are much more likely to generalize to the general population, distortions in the delivery of the intervention may occur. Research requires measures of the intervention fidelity (i.e., the degree to which the intervention is delivered in the manner intended by the researcher) and treatment dose (the extent to which the subject participates in or receives the full intervention). A study of a school-based intervention delivered by regular classroom teachers needs not only a strong method for teacher training and monitoring but also explicit measures of how the teachers delivered the intervention and the degree to which students attended and/or received the full intervention. Such monitoring may include a mix of quantitative measures (e.g., curriculum checklists, student attendance records, self-reports of teacher satisfaction with the intervention) and qualitative assessments (e.g., ethnographic observations of classrooms while lessons are being taught, focus groups of teachers, or individual interviews). Other measures (i.e., triangulation) may be used to confirm teacher reports of intervention fidelity or treatment dose, such as asking students to complete a questionnaire about simple concepts or facts from the intervention, to test whether children were exposed to the relevant lessons.

ETHICAL ISSUES

The nature of research in the field of DBP introduces some ethical issues that, although not necessarily unique, may occur with greater frequency or complexity than in other fields. This section illustrates the range of issues that may be encountered.

IMPLICATIONS FOR RESEARCH TRAINING IN DEVELOPMENTAL-BEHAVIORAL PEDIATRICS

The eclectic and complex nature of research in DBP requires that research training be broad. The mixing of qualitative and quantitative methods, the need for the development of valid and reliable measures for complex constructs, the importance of sociocultural influences, and the need for repeated measurements over time mandate rich and varied educational experience in research methods. Training should include a strong foundation in the basics of research design, as well as a focus on qualitative methods, instrument and survey development, and the use of large datasets. Skills in clinical epidemiology and evidence-based medicine are important for performing research related to diagnosis, screening, and prevention, as well as for understanding the validity and strength of findings. An understanding of statistical methods for data analysis, both bivariate and multivariate, is important for both the appropriate design of studies and the evaluation of study results. DBP researchers should also be educated in the principles of the responsible conduct of research, especially the special protection necessary for children and other vulnerable populations. Finally, training in all aspects of scientific communication, for presentations, publications, and teaching, must be provided.

In addition to the need for a broad-based training in research methods, the specific issues elucidated previously have important and specific implications for research training of developmental-behavioral pediatricians. These implications are discussed as follows.

Training in Quasi-experimental and Observational (Epidemiological) Research Designs

The majority of research in DBP does not involve double-blind, randomized, controlled trials (RCTs). Double-blind RCTs are conducted in studies of psychopharmacological therapy for such conditions as ADHD and autistic spectrum disorders, and single-blind RCTs are conducted for behavioral and educational interventions for the treatment or the prevention of developmental and behavioral disorders. Examples of the latter include the High/Scope Perry preschool study5 and the Hawaii home visiting study.6 However, many important nonpharmacological interventions in DBP are difficult to randomize. New educational interventions in the school setting, for example, are likely to be offered to whole classes or schools rather than to randomly selected students, with other classes in the same school or other schools in the same district acting as controls after being matched on a variety of characteristics. These “quasi-experimental” designs play an important role in DBP research.

Research training should, therefore, include education in quasi-experimental designs. A quasi-experimental design is similar to an experimental design except that it lacks the important step of randomization.7 The most common type of quasi-experimental design involves the use of nonequivalent matching groups. One cohort of children receives an intervention, whereas another matched cohort acts as a control or receives an alternative intervention. Quasi-experimental designs such as this, although frequently the only possible design for some nonpharmacological interventions, suffer from the threat to their validity of selection bias. Education concerning the identification of selection bias and methods to reduce its effect (such as matching, sample stratification, and adjusting for potential confounders) is important for the developmental-behavioral researcher.8

Furthermore, researchers in DBP frequently seek to study the effects of harmful and protective factors on childhood outcomes in normative or at-risk populations or to elucidate underlying constructs associated with or causing various outcomes. The study of naturally occurring constructs or of potentially harmful factors leads to choosing observational designs rather than experimental designs.8

Observational designs in DBP research are usually single- or double-cohort studies. Single-cohort studies usually involve monitoring a group of children and looking for factors that are predictive of outcomes. For example, the researcher may want to monitor a group of children with intrauterine exposure to cocaine, or with very low birth weight, and determine whether breastfeeding or maternal expectations lead to improved developmental outcomes. Double-cohort studies usually involve a comparison group. For example, a study may compare the incidence of behavior problems in cocaine-exposed infants when they reach preschool with that in a matched group of children. Single-cohort studies may lead to spurious results because of confounding factors. Double-cohort studies, like quasi-experimental designs, may be threatened by selection bias. The DBP researcher should receive in-depth training in these observational study designs and in methods to adjust for confounding and to minimize selection bias.

In addition, the researcher should receive training to understand concerns about inferring causality from results of observational studies and to devise strategies to enhance causal inference (e.g., inclusion and exclusion criteria, matching, and stratification). The principles of strength of evidence for causality—temporality, effect size, dose-response relationships, biological plausibility, reversibility, specificity of results, and consistency of results across studies—should be clearly understood.

Training in Qualitative Methods

Qualitative research designs play an important role in developmental-behavioral research. For example, in one study, investigators sought to understand Latina mothers’ cognition and attitudes concerning stimulant medication for ADHD and how these factors might determine adherence to medication regimens and resistance to starting drug therapy.9 Qualitative methods are the best approach to this type of research question, with which investigators seek to understand the perspectives of persons or groups and to develop and revise research hypotheses. Therefore, a strong foundation in qualitative methods is important for DBP researchers. Training should include providing an understanding of the types of research questions that qualitative methods are best suited to answer, skills in the use of common ethnographic methods, facility with methods used for data coding and data reduction, and familiarity with methods used to ensure trustworthiness of qualitative research results.1013

Training in the Development and Validation of Testing Instruments and Scales

Many of the outcomes and constructs of DBP lack well-standardized or validated measures. Furthermore, even well-validated and reliable measures developed for a general population may not be appropriate for use in a special population. Therefore, the development and validation of such measures are frequent subjects of a research study or are common components of a larger research project. For example, in one study, investigators sought to measure self-efficacy and expectations for self-management among adolescents with chronic disease (diabetes) and to determine the effects of these factors on disease management outcomes.14 However, there existed no scale for measuring self-efficacy or measuring expectations for self-management of diabetes. Therefore, the researchers had to develop their own scales and test the reliability and validity of those scales before answering the underlying research question. In another study, researchers wanted to determine whether the Pediatric Symptom Checklist,15 a commonly used screen for behavior problems in a general population, was valid for use in a chronically ill population.16 In this case, the researchers sought to test the construct validity of a well-validated scale on a new population.

Therefore, research training should include skills in test development, including testing for reliability (with measures such as test-retest reliability and interrater reliability), internal consistency, and validity. The researcher should be familiar with the different types of validity, including content and sampling validity, construct validity, and criterion-related validity, and be able to use methods that assess them.17

Training in the Use of Large Secondary Datasets

Research publications increasingly reflect the efforts of researchers to mine large secondary datasets, including federally funded national databases, administrative databases, and electronic medical records, for information related to delivery of care and outcomes in DBP. This type of research has been especially fruitful in the study of ADHD. In one published study, the researchers used the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey to study regional and ethnic differences in the diagnosis of ADHD and receipt of psychotropic medications for that diagnosis.18 In another, investigators used health maintenance organization (HMO) data to compare total health care costs for children with and without ADHD.19 Researchers at the Mayo Clinic have used their computerized medical records database, which has information on 95% of the population in Olmstead County, Minnesota, from 1977 to the present. They have studied ADHD, autism, psychostimulant treatment, and learning disabilities, among other topics.2022 Finally, Rappley and colleagues used Medicaid database information to sound an alarm about apparent excessive prescription of psychotropic medication for preschool children.23

These studies demonstrate that large datasets contain potential answers to clinical, epidemiological, policy, and health finance questions important to DBP. Research training should provide the knowledge and skills to evaluate these large datasets and to use appropriate sampling and statistical methods in subsequent data analysis. Training should also focus on the types of information collected by cross-sectional and longitudinal national survey datasets, as well as the advantages and disadvantages of using national survey data to answer research questions. Familiarity with health plan administrative datasets, electronic medical records, and disease registries may also be useful for the researcher interested in epidemiological questions concerning disease rates and distribution, utilization of resources, and resulting costs.

Training in Multivariate Statistical Analyses

As a consequence of the frequent use of quasi-experimental and observational study designs in DBP research, training in statistical methods that adjust for confounding factors and that determine unique and independent contributions of hypothesized factors to patient outcomes is essential. Research training should focus on such commonly used statistical techniques as multiple linear regression,24 analysis of covariance (ANCOVA), and logistic regression.25 Although training goals may vary in the level of expertise from “educated consumer” of statistical services to independent producer of statistical analyses, the DBP researcher should be skilled in the interpretation of the results of these analyses, knowledgeable about the different types of statistical models, and able to recognize the pitfalls and limitations of these techniques.

Measurement of psychological or behavioral characteristics with scales frequently necessitates an analysis of data for the underlying factors or constructs embodied by the measured variables. Factor analysis is employed to reduce measured variables to a smaller number of underlying “latent” variables. Factor analysis is frequently used to explore and confirm the construct validity of a new scale or a previously validated scale for use in a new population. In addition, factor scores may be used to substitute for variables in other statistical analyses. Because research in DBP often involves the development of new measures for abstract outcomes, factor analysis is a useful statistical method for DBP researchers. For example, factor analysis was used to develop new scales in the previously noted study14 in which investigators sought to compare self-efficacy and expectations for diabetic management to diabetes self-management outcomes. They then used the scores on these scales, including a separate score for each of two identified factors, in multiple regression analyses of the relationships between these constructs. In another previously cited study,16 researchers used factor analysis to compare items on the Pediatric Symptom Checklist15 in a chronically ill population with those in a general population.

Therefore, an understanding of the role of factor analysis in the development and validation of testing instruments and scales is important for the DBP researcher. Familiarity with methods of extraction of factors from the collected data, procedures for keeping and discarding factors, and other aspects of factor analysis are an important part of research training.2628

Training in Neurobiological and Genetic Science

The frequently used multidisciplinary approach to DBP, as well as the importance of the biopsychosocial model, requires the DBP researcher to collaborate with other scientists who use research techniques by which they attempt to elucidate the neurobiological and genetic bases for development, behavior, and learning. The researcher needs to be familiar with and understand these basic sciences and scientific methods in order to interpret the scientific literature and to generate new research questions for investigation.

A growing body of research has focused on the use of neuroimaging techniques to elucidate brain function and anatomical location of activation during behavioral and psychological tasks. Functional magnetic resonance imaging (fMRI) has become an important tool in developmental-behavioral research. Unlike positron emission tomography (PET) and single photon emission computed tomography (SPECT), fMRI does not include the injection of radioactive materials. Therefore, children can undergo imaging repeatedly, which allows for study during different disease states or throughout developmental changes. It also allows the researcher to study healthy children at low risk for the disorder under investigation. For example, using fMRI, researchers have sought to localize the areas of brain activation with attention or reading tasks in children with ADHD or dyslexia and compare those activation patterns with patterns in normal children.29,30 Other researchers have used brain proton magnetic resonance spectroscopy to identify children with brain creatine deficiency who have global developmental delay.31 It is likely that functional neuroimaging techniques will play an important role in the future study of the neurobiological basis of developmental and behavioral problems or conditions. Future researchers should receive training in the science of these techniques to enable them to collaborate with neuroradiologists in answering questions that span the spectrum of the biopsychosocial model.

Similarly, training in the genetics of developmental and behavioral disorders is important for researchers. Understanding the role of genetics will empower the researcher to incorporate genetics into research hypotheses and methods. One area that should be considered for inclusion in research training is quantitative behavioral genetics.32 In this field, investigators seek to determine the proportion of variance in behaviors resulting from heritability, shared environment (family, neighborhood, home environment), and unshared environment (e.g., peers, teachers, differential parental treatment, illnesses). For example, one article focused on the quantitative behavioral genetics of child temperament.33

Another important area for research is the association of behavioral phenotypes with molecular genetic findings and variations. Behavioral and psychoeducational profiles have been elucidated through research for velocardiofacial, Williams, Down, Prader-Willi, fragile X, and Turner syndromes, among others.34 Studies have shown associations of these behavioral and psychological characteristics with specific molecular genetic patterns. The availability of molecular genetic techniques has also allowed scientists to study behavioral phenotypes of subjects with “milder” genetic deficits. For example, in one study, researchers found an association of fragile X premutation (carriers) with autistic spectrum diagnosis through the use of molecular genetic studies.35 Other researchers have been studying polymorphisms in specific genes, such as the dopamine D4 receptor gene (D4DR) and the serotonin transporter promoter gene (5-HTTLPR), and finding associations with ADHD and temperamental traits.36,37 Collaboration between DBP researchers and geneticists and the use of molecular genetics technology are likely to yield important findings concerning the etiology of developmental-behavioral disorders and normative behavior patterns.

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