TABLE 3.

Hybrid Design Characteristics and Key Challenges

Study Characteristic	Hybrid Trial Type 1	Hybrid Trial Type 2	Hybrid Trial Type 3
Research aims	Primary aim: determine effectiveness of a clinical intervention Secondary aim: better understand context for implementation	Coprimary aim*: determine effectiveness of a clinical intervention Coprimary aim: determine feasibility and potential utility of an implementation intervention/strategy	Primary aim: determine utility of an implementation intervention/strategy Secondary aim: assess clinical outcomes associated with implementation trial
Research questions (examples)	Primary question: will a clinical treatment work in this setting/these patients? Secondary question: what are potential barriers/facilitators to a treatment’s widespread implementation?	Coprimary question*: will a clinical treatment work in this setting/these patients? Coprimary question: does the implementation method show promise (either alone or in comparison with another method) in facilitating implementation of a clinical treatment?	Primary question: which method works better in facilitating implementation of a clinical treatment? Secondary question: are clinical outcomes acceptable?
Units of randomization	Patient, clinical unit	Clinical effectiveness: see type I Implementation: see type III, although may be nonrandomized, for example, case study	Provider, clinical unit, facility, system
Comparison conditions	Placebo, treatment as usual, competing treatment	Clinical effectiveness: see type I Implementation: see type III, although may be nonrandomized, for example, case study	Provider, clinical unit, facility, system: implementation as usual, competing implementation strategy
Sampling frames	Patient: limited restrictions, but some inclusion/exclusion criteria Provider, clinical unit, facility, system: choose subsample from relevant participants	Patient: limited restrictions, but some inclusion/exclusion criteria Providers/clinics/facility/systems; consider “optimal” cases	Provider/clinic/facility/system: either “optimal” cases or a more heterogeneous group Secondary: all or selected patients included in study locations
Evaluation methods	Primary aim: quantitative, summative Secondary aim: mixed methods, qualitative, process-oriented, could also inform interpretation of primary aim findings	Clinical effectiveness aim: quantitative, summative Implementation aim: mixed method; quantitative, qualitative; formative and summative	Primary aim: mixed-method, quantitative, qualitative, formative, and summative Secondary aim: quantitative, summative
Measures	Primary aim: patient symptoms and functioning, possibly cost Secondary aim: feasibility and acceptability of implementing clinical treatment, sustainability potential, barriers and facilitators to implementation	Clinical effectiveness aim: patient symptoms and functioning, possibly cost effectiveness Implementation aim: adoption of clinical treatment and fidelity to it, as well as related factors	Primary aim: adoption of clinical treatment and fidelity to it, as well as related factors Secondary aim: patient symptoms, functioning, services use
Potential design challenges	Generating “buy in” among clinical researchers for implementation aims Insuring appropriate expertise on study team to conduct rigorous Secondary aim These studies will likely require more research expertise and personnel, and larger budgets, than nonhybrids	Generating “buy in” among implementation researchers for clinical intervention aims These studies will require more research expertise and personnel, as well as larger budgets, than nonhybrids Insuring appropriate expertise on study team to rigorously conduct both aims “Creep” of clinical treatment away from fidelity needed for optimal effectiveness IRB complexities with multiple types of participants	Primary data collection with patients in large, multisite implementation trials can be unfeasible, and studies might need to rely on subsamples of patients, medical record review, and/or administrative data. Patient outcomes data will not be as extensive as in traditional effectiveness trials or even other Hybrid types, and might be insufficient to answer some questions “Creep” of clinical treatment away from fidelity needed for optimal effectiveness IRB complexities with multiple types of participants

^*In a grant application, one of these aims/research questions might take precedence, for example in a case where the test of an implementation intervention/strategy is exploratory. Yet, for the purposes of this table, we listed these dual aims/research questions as “coprimary.”

IRB indicates Institutional Review Board.