Background

In the past two decades, the massive scale-up of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) has led to significant reductions in malaria mortality and morbidity. Nonetheless, the malaria burden remains high, and a dozen countries in Africa show a trend of increasing malaria incidence over the past several years. This underscores the need to improve the effectiveness of interventions by optimizing first-line intervention tools and integrating newly approved products into control programs. Because transmission settings and vector ecologies vary from place to place, malaria interventions should be adapted and readapted over time in response to evolving malaria risks. An adaptive approach based on local malaria epidemiology and vector ecology may lead to significant reductions in malaria incidence and transmission risk.

Methods/design

This study will use a longitudinal block-cluster sequential multiple assignment randomized trial (SMART) design with longitudinal outcome measures for a period of 3 years to develop an adaptive intervention for malaria control in western Kenya, the first adaptive trial for malaria control. The primary outcome is clinical malaria incidence rate. This will be a two-stage trial with 36 clusters for the initial trial. At the beginning of stage 1, all clusters will be randomized with equal probability to either LLIN, piperonyl butoxide-treated LLIN (PBO Nets), or LLIN + IRS by block randomization based on their respective malaria risks. Intervention effectiveness will be evaluated with 12 months of follow-up monitoring. At the end of the 12-month follow-up, clusters will be assessed for “response” versus “non-response” to PBO Nets or LLIN + IRS based on the change in clinical malaria incidence rate and a pre-defined threshold value of cost-effectiveness set by the Ministry of Health. At the beginning of stage 2, if an intervention was effective in stage 1, then the intervention will be continued. Non-responders to stage 1 PBO Net treatment will be randomized equally to either PBO Nets + LSM (larval source management) or an intervention determined by an enhanced reinforcement learning method. Similarly, non-responders to stage 1 LLIN + IRS treatment will be randomized equally to either LLIN + IRS + LSM or PBO Nets + IRS. There will be an 18-month evaluation follow-up period for stage 2 interventions. We will monitor indoor and outdoor vector abundance using light traps. Clinical malaria will be monitored through active case surveillance. Cost-effectiveness of the interventions will be assessed using Q-learning.

Discussion

This novel adaptive intervention strategy will optimize existing malaria vector control tools while allowing for the integration of new control products and approaches in the future to find the most cost-effective malaria control strategies in different settings. Given the urgent global need for optimization of malaria control tools, this study can have far-reaching implications for malaria control and elimination.

Background

Tobacco use remains the leading cause of death and disability in the USA and is disproportionately concentrated among low socioeconomic status (SES) populations. Community Health Centers (CHCs) are a key venue for reaching low SES populations with evidence-based tobacco cessation treatment such as Quitlines. Electronic health record (EHR)-based interventions at the point-of-care, text messaging (TM), and phone counseling have the potential to increase Quitline reach and are feasible to implement within CHCs. However, there is a lack of data to inform how, when, and in what combination these strategies should be implemented. The aims of this cluster-randomized trial are to evaluate multi-level implementation strategies to increase the Reach (i.e., proportion of tobacco-using patients who enroll in the Quitline) and Impact (i.e., Reach × Efficacy [efficacy is defined as the proportion of tobacco-using patients who enroll in Quitline treatment that successfully quit]) and to evaluate characteristics of healthcare system, providers, and patients that may influence tobacco-use outcomes.

Methods

This study is a multilevel, three-phase, Sequential Multiple Assignment Randomized Trial (SMART), conducted in CHCs (N = 33 clinics; N = 6000 patients). In the first phase, clinics will be randomized to two different EHR conditions. The second and third phases are patient-level randomizations based on prior treatment response. Patients who enroll in the Quitline receive no further interventions. In phase two, patients who are non-responders (i.e., patients who do not enroll in Quitline) will be randomized to receive either TM or continued-EHR. In phase three, patients in the TM condition who are non-responders will be randomized to receive either continued-TM or TM + phone coaching.

Discussion

This project will evaluate scalable, multi-level interventions to directly address strategic national priorities for reducing tobacco use and related disparities by increasing the Reach and Impact of evidence-based tobacco cessation interventions in low SES populations.

Naltrexone (NTX) is an opioid receptor antagonist used to prevent alcoholism relapse. This trial examines how to define “non-response” to treatment with NTX and what treatments are most effective for those who do or do not respond to the initial treatment.

Researchers in this study are developing an adaptive treatment for adolescent marijuana users. They are studying the use and combination of several efficacious treatments, including behavioral therapy, contingency management, behavioral parent training, and working memory training via a SMART trial.

Researchers in this study are developing an adaptive treatment to address suicidality in college students seeking services at college counseling centers. They are developing the first empirically validated approach to sequence treatments for students seeking services.

This study compares two types of interventions for youth (ages 10-15) with conduct disorders. Participants received either a teen-focused or parent-focused intervention. The appropriate intensity of the interventions was also studied.

The aim of this SMART is to understand whether to begin with medication or behavioral therapy for children with ADHD, and whether to intensify or augment initial treatment for children who do not respond to treatment.

This study will compare two types of intensive, daily instruction for children with autism spectrum disorder (ASD) who use only minimal verbal communication. Earlier research has shown that even after early language-skills training, about one-third of school-aged children with ASD remain minimally verbal. Researchers plan to enroll 200 children in four cities: Los Angeles, Nashville, New York City, and Rochester, N.Y.

This project targets African American adolescents with obesity and their parents. SMARTs are used to develop an adaptive intervention that increases skills in changing dietary, exercise, and sedentary behaviors.

Patients suffering from bipolar disorder are assigned to one of two mood stabilizers. A SMART design is used to determine the appropriate treatment for patients who develop depression.

A SMART design is being implemented to develop an adaptive intervention to increase treatment engagement and decrease cocaine use for patients who are cocaine dependent. The study also examines whether patient choice of care affects patient outcomes.

Studies show that the use of stimulants for the control of ADHD in youth leads to a reduction in height gain. This study uses a SMART design to examine the effectiveness of temporary breaks in medicinal treatments and caloric supplementation for the treatment of stimulant-induced weight and growth suppression.

This project aims to develop an adaptive intervention for persistent insomnia. Researchers are using a SMART design to determine the best sequencing of cognitive behavioral therapy and medication for persistent insomnia.

Researchers have developed an intensive relapse-prevention program for pregnant women who abuse drugs. A SMART design is being used to develop an adaptive intervention where the intensity and scope of the relapse-prevention program is adjusted based on the evolving status of each woman.

Between 50% and 70% of people living with HIV are nicotine dependent. This SMART examines how and when to apply contingency management and standard treatment to promote smoking cessation in this population.

For youth with OCD, the most common treatments are cognitive-behavioral therapy (CBT), pharmacological treatment, or both. Up to 30% of patients may not benefit from their initial treatments. Researchers will employ a SMART to determine the optimal treatment sequence for participants dependent on whether or not they respond to their initial treatment.

In order to develop communication skills among school-aged children who are nonverbal, this project employs a SMART design to test a novel intervention. The intervention includes components that focus on spoken language and the use of a speech-generating device (e.g., iPad). The SMART design provides the data needed to define response and nonresponse to the intervention and identify the best treatment sequence.

This SMART is cluster-randomized. Randomization occurs at the clinic level. The aim of the study is to develop an adaptive quality improvement strategy designed to enhance the implementation of an evidence-based mental health intervention. Outcomes are measured at the patient level.

Adolescents suffering from depression begin treatment with interpersonal psychotherapy. This pilot project employs a SMART design to help establish treatment rules regarding when and in what way to intensify treatment.

This project will develop an adaptive intervention to improve ​social connectedness​, academic engagement, and other skills among school-aged children with autism spectrum disorder​. Treatment for each participant includes some combination of a playground-based intervention, a classroom-based intervention, a peer-mediated intervention, and a parent-assisted intervention.​ This pilot project will address feasibility and acceptability concerns and will provide preliminary data for a full-scale SMART.

This pilot project uses a SMART design to develop an adaptive intervention for children with depression. Dr. Eckshtain aims to develop decision rules regarding the use of cognitive behavioral treatment, caregiver–child treatment, or both. The goal is to develop an adaptive treatment protocol for depressed children.

This project aims to develop an adaptive intervention for families where the mother has ADHD and the child is at genetic and environmental risk for ADHD. Researchers are using SMART to determine how to use behavioral training or medication for mothers separately, in sequence, or in combination, to improve the quality of parenting and prevent the progression of ADHD in children.

Contingency management (CM) is a treatment used in Cocaine Misuse where patients are rewarded for following treatment guidelines. In this study, researchers are comparing CM to treatment without incentives using a SMART design. They are also testing the timing and the length of the CM.