A placebo prognostic index (PI) as a moderator of outcomes in the treatment of adolescent depression: Could it inform risk-stratification in treatment with cognitive-behavioral therapy, fluoxetine, or their combination?

Introduction: Researchers have proposed that predicting who is a likely placebo responder may help guide treatment allocations to treatment regimens that differ in intensity. Methods: We used data from the Treatment of Adolescent Depression Study (TADS) in which adolescents (n = 439) were randomized 1:1:1:1 to placebo, cognitive-behavioral therapy (CBT), medications (MEDs), or their combination (COMB). We developed a prognostic index (PI) in the placebo group to predict self-reported (RADS) and observer-rated (CDRS) depression outcomes using elastic net regularization. We explored whether the PIs moderated outcomes in the treatment conditions. Results: PI-CDRS was predicted by multiple variables but it did not moderate outcomes. PI-RADS was predicted by baseline severity, age, sleep problems, expectations, maternal depression, and the action stage of change. It moderated outcomes such that there were treatment differences for less placebo-responsive patients. For participants prone to placebo response, type of treatment had no statistically significant impact on outcomes. Baseline depression severity accounted for this effect: treatment differences were small and non-significant for patients with milder depression but larger in more severely depressed patients. Discussion: Future work should investigate whether multiple variable explain outcomes beyond severity as well as complex interactions between severity and other variables.

Assessing patient readiness for personalized genomic medicine.

The Human Genome Project and the continuing advances in DNA sequencing technology have ushered in a new era in genomic medicine. Successful translation of genomic medicine into clinical care will require that providers of this information are aware of the level of understanding, attitudes, perceived risks, benefits, and concerns of their patients. We used a mixed methods approach to conduct in-depth interviews with participants in the NCI-funded Breast Cancer Family Registry (BCFR). Our goal was to gain a better understanding of attitudes towards different types and amounts of genomic information, current interest in pursuing genomic testing, and perceived risks and benefits. We interviewed 32 women from the six BCFR sites in the USA, Canada, and Australia. In this sample of women with a personal or family history of breast cancer, we found high acknowledgement of the potential of genetics/genomics to improve their own health and that of their family members through lifestyle changes or alterations in their medical management. Respondents were more familiar with cancer genetics than the genetics of other diseases. Concerns about the testing itself included a potential sense of loss of control over health, feelings of guilt on passing on a mutation to a child, loss of privacy and confidentiality, questions about the test accuracy, and the potential uncertainty of the significance of test results. These data provide important insights into attitudes about the introduction of increasingly complex genetic testing, to inform interventions to prepare individuals for the introduction of this new technology into their clinical care.