DAY 2 Single-Case Design Drug Intervention Research Tom Kratochwill

Goals of the Presentation Present Some Considerations in the Use of Single-Case Designs in Drug Intervention Research; Review the Role of Placebo Controls; Present Considerations for Addressing Carryover Effects; Present Options for Conducting Single-and Double-Blind Assessments; Discuss the Importance of Assessing Side Effects; Present Optional Designs Used in Drug Intervention Research.

The Importance of Single-Case Design Drug Intervention Research The number of children and adults with disabilities that receive psychoactive drugs for their condition has increased; The number of children receiving more than one drug for a disability has increased (called polypharmacy); The number of new drugs to treat children with learning and behavior disorders has increased; The likelihood of involving children in an intervention for academic and/or behavioral protocol who are already on some psychoactive drug is high.

Drug Intervention Research Considerations Researchers in education and the social sciences may have the opportunity to review drug intervention research and/or comparative intervention research; Researchers in education and the social sciences may have an opportunity to collaborate on research involving drug interventions; Individuals interested in conducting research on drugs must collaborate with health/medical professionals who have expertise in the drug(s) under consideration; Institutional Review Board (IRB) evaluation of drug intervention research is extensive and very detailed.

Single-Case Design Drug Research Developments Early drug intervention research typically involved a comparison of a drug to placebo (i.e., an intervention that “looked like” the active drug); More recent research typically involves a “comparative effectiveness” protocol in which the drug is compared to a credible alternative (e.g., function-based intervention, alternative drug) and placebo; Most current research on drug intervention involves randomized controlled trials with large Ns.

Contributions of Single-Case Design Methodology to Drug Intervention Research Useful in pilot studies in which a new drug is tested (in the health and medical field it is called N-of-1 trials); Useful in applications in which the disorder or problem is rare or low incidence; Useful in “pull out” of participants in a randomized controlled trial who may not respond to a particular drug intervention (based on type, dosage, etc.).

Single-Case Design and Drug Evaluation Topics Nomenclature Carryover Effects Single-and Double Blind Assessments Side Effect Assessments

Nomenclature A refers to baseline; B refers to the active drug; C refers to the second active drug if used in the experiment or another intervention (as in comparative effectiveness research with academic and/or social/psychological interventions); A ‘ refers to the placebo phase or typically the phase intermediate between the no-intervention baseline (A) and the drug intervention condition (B).

Carryover Effects in Drug Research Carryover effects refer to the possible biological influence of the active drug (B) into the next phase of the study [placebo phase (A’) or active drug (B) phase]; Carryover effects may contaminate the next condition and lead to inaccurate conclusions about the effect of the drug under consideration in that condition (e.g., drug B may affect the placebo A’ phase, or drug C phase).

Controlling Carryover Effects To control carryover effects the researcher must have knowledge of the drug’s biological action. For example, information on the drug’s titration and wash out period will be essential; A proper assessment of the drug’s biological effects will be needed (e.g., blood and urine monitoring); Typically, a baseline condition following the active drug will be scheduled that is long enough to assess the continuing effects of the drug. In this assessment, phase length can be adjusted.

Double-Blind/Masked Assessments in Drug Research Patient knowledge of participating in an active drug condition may bias their response to the drug; Similarly, experimenter knowledge of which condition the patient is assigned to or experiencing can bias results; Reducing bias in drug research is a concern similar to that of reducing bias in observational assessment when human observers are used.

Single-and Double Blind Assessments to Reduce Bias “Blind” or masked assessments are considered important in drug research in order to reduce bias of the drug’s effects. Placebo controls are scheduled to address this issue but blind or masked assessments should be added to the research protocol; Single-blind assessment refers to the blinding/masking of the active drug condition to the patient or participants; Double-blind assessment would include a blinding/masking of drug condition to both the patient and experimenter(s) in the drug research protocol.

Side Effects in Drug Research Drugs may have single/multiple side effects and the researcher must have good knowledge of potential side effects; Side effect monitoring is essential in drug research; Side effect monitoring will be required by the research IRB.

Side Effects Assessment in Drug Research Side effect monitoring protocols will typically be developed for assessment of specific drugs; Side effect assessment will typically involve multiple measures to cast a wide net on possible side effects and their influence; Side effect assessment will occur throughout the drug intervention and no-intervention conditions as well as follow-up phases; Side effect response, if negative, may result in some type of intervention and may cause the termination of the experiment.

Some Optional Drug Intervention Designs Withdrawal Designs Multiple Baseline Designs Alternating Intervention Designs Complex or Combined Designs Randomized Designs Based on the Above Options

Basic Drug Design Examples Reversal/Withdrawal Designs Multiple Baseline Designs Alternating Intervention Designs

Example Options for Withdrawal Designs A/A’/A/A’ A/A’/B/A’/B A/A’/A/A’/B/A’/B A/A’/B/A’/B/A’/C/A’/C

Withdrawal Drug Design Considerations Effects of the intervention must be reversible in the A’/B/A’/B…series (e.g., return to baseline or near baseline levels); May be ethical issues involved in reversing behavior back to baseline or placebo (A or A’); May be a complex study to run when multiple conditions need to be compared (e.g., A/A’/B/A’/B/A’/C/A’/C/A’/C…); There are order effects in withdrawal designs; There may be carryover effects in withdrawal designs when alternative drug interventions are compared; There may be interactive effects when two or more drugs are compared.

Multiple Baseline Design Description The traditional multiple baseline design is applied across units(participants), across behaviors, across situations. In drug research, the application will be across participants.

Multiple Baseline Design Drug Intervention Considerations The design is typically used to demonstrate the effect of one drug independent variable on some outcome(s); The active drug condition (B) is typically preceded by a placebo condition (A’); The design depends on the “independence” of the multiple baselines (across participants); As in traditional applications of the design, there can be practical as well as ethical issues in keeping individuals on baseline for long periods of time (e.g., especially in the last series).

Alternating Intervention Designs Alternating intervention designs have possible application in drug research when the alternating conditions can be spaced across sessions/time so as to eliminate carry over effects of a particular drug; The design has application when the researcher can compare and active drug (B) to placebo (A’); The design has possible application when the researcher compares two drugs (B and C) with relatively rapid “wash out” effects of both drugs.

Alternating Intervention Design Drug Intervention Considerations Outcome measures must demonstrate a reversal or partial reversal during alternation of the drug(s) or non-drug interventions; There is the possibility of carryover/interaction effects as conditions are alternated rapidly within the context of the drug(s) being tested; Comparing more than two drug interventions in the design will be very challenging.

Questions and Discussion