Behavioral scientist practitioners engage with RCTs in three main ways (Spring, 2007):
In this module, you'll learn:
Do you think that 2 participants per treatment group would be considered sufficient in a contemporary RCT?
Cognitive-behavioral therapy (CBT) is a style of therapy that focuses on changing troublesome thoughts, feelings, and behavior. CBT for the treatment of an anxiety disorder has been studied extensively via RCTs.
A systematic review combining evidence from many RCTs conducted in different settings, with different populations, and somewhat different protocols was commissioned by the Cochrane Collaboration. The review found remission of an anxiety disorder in 56% of anxious children treated with CBT - twice the remission rate found in controls (James, Soler, Weatherall, 2005). As a result of the accumulation of high-quality evidence in this area, CBT is now considered the front-line treatment for childhood anxiety disorders.
The usefulness of a trial depends on the extent to which it lets us validly infer that the experimental treatment caused an outcome. The ability to make valid inferences depends on how well the investigator designed, conducted, and reported various procedures to minimize bias in the study.
A factory shutdown occurred during the course of Dr. Austin's study, causing many town residents to lose their jobs. Consider a scenario in which all of the children in Dr. Austin's control group and none of the children in her treatment group had a parent laid off in the shutdown. If the treated children were less depressed than the control children at the end of the study, Dr. Austin would not know what caused the difference. It might have been her treatment. Just as plausibly it might have been that the children in her treatment experienced a lower number of stressful life events than the control children. Fortunately, randomizing patients to conditions increases the probability that the treatment and control groups will have similar exposure to extraneous events.
Testing Efficacy vs. Effectivenessa>
An efficacy trial answers the question: "Does this intervention work under optimal conditions?" An effectiveness trial answers the question: "Does this intervention work under usual conditions?"
Efficacy trials are sometimes called explanatory trials, whereas effectiveness trials are also known as pragmatic trials.
Dr. Austin mulls over whether to conduct a pragmatic or an explanatory trial. She would like her findings to generalize to the broadest possible population of depressed adolescents, so she leans toward doing a pragmatic trial. However, she has doubts about whether the treatment will work with adolescents who have substance abuse disorders or symptoms of antisocial personality. After talking with a statistician, she realizes that she would need a much larger sample size to conduct a pragmatic trial, because she expects the treatment effect to be less consistent than it would be in an efficacy trial. She decides that her first priority is to learn whether her treatment can work, and conducts an efficacy trial.
An investigator wants to test the effectiveness of a school-based violence prevention intervention. He identifies his population of interest as public school children in grades 9-12 in the city where he lives, whose parents allow them to participate.
Dr. Jones conducted a placebo-controlled RCT testing the efficacy of a new medication to prevent recurrent heart attacks. Although he randomized patients to drug versus placebo, more overweight people were assigned to his placebo condition. Because being overweight heightens the risk of heart attack, a lower heart attack rate among drug- than placebo-treated patients could occur for one of two reasons. The medication that the patients received could have lowered the risk of heart attack. Alternatively, patients randomized to the drug treatment group could have been less at risk because they were less overweight.
A researcher wants to test a teacher-focused intervention in schools. However, she worries that if she randomizes teachers within a school to receive the intervention or not, there may be contamination. She fears that teachers will talk to each other about the study, and that control group teachers will observe intervention teachers' behavior and model it, even though they were not randomized to receive the intervention. In response, the researcher decides to randomize different schools to receive the teacher intervention or no intervention.
If after 10 randomizations, there are 7 patients assigned to intervention and 3 assigned to control, the coin toss will become biased. Then, rather than having 50/50 chance of being assigned to either condition, the next patient will be given a 2/3 chance of being assigned to the under-represented condition and a 1/3 chance of being assigned to the overrepresented one. This procedure requires keeping track of imbalances throughout the trial. In smaller trials, imbalances can still result.
The investigator starts with off with an urn containing a red ball and a blue ball to represent each condition. If the first draw pulls the red ball, then the red ball is replaced together with a blue ball, increasing the odds that blue will be chosen on the next draw. This continues, replacing the chosen ball and one of the opposite color on each draw. The procedure works best at preventing imbalance when final sample size will be small.
Neuroimaging and biomarker data can objectively track the course of a health condition. A device called a MEMS cap, which records the opening of a prescription bottle, measures medication compliance objectively. An accelerometer that counts movements directly measures physical activity.
Q: If a person scores as depressed on a questionnaire but doesn't qualify for a depression diagnosis on a semi-structured interview, does the condition of depression exist in that individual?
A suicide attempt would be considered an SAE in a study of any treatment. The SAE needs to be reported regardless of whether it bears any relationship to the treatment or the problem being studied.
An investigator wishes to understand how a parenting intervention improves symptoms of attention deficit hyperactivity disorder (ADHD) in children. The investigator hypothesizes that the intervention achieves its benefit by improving communication and decreasing conflict in the parent-child relationship.
To test mediation, the investigator would examine:
In a multi-site study involving 5,000 women, an investigator studied the efficacy of an intervention to reduce depression among women with breast cancer. An average pre-post decrease of 5 points on a depression scale was observed. This change was statistically significant, probably due to the very large sample size and power to detect very small effects. However, even though depression scores decreased after the intervention, the average score remained in the clinical range, indicating severe depression. Do you think this intervention was effective?
A post hoc analysis of an RCT found an interaction indicating that treating depression after a heart attack decreased the risk of repeat heart attacks for white men, but increased the risk for white women. On the basis of that evidence, an insurance company decides not to pay for depression treatment for women who become depressed after having a heart attack. The company says their decision reflects evidence-based practice. Do you agree?
Mistrust of medical and scientific institutions, or language or cultural barriers can make minority recruitment challenging.
To address these challenges, an investigator might: