Institute for Clinical Research and Health Policy Studies

The Johns Hopkins University-Tufts Trial Innovation Center (JHU-Tufts TIC) was established in 2016 to provide Clinical and Translational Science Award (CTSA) investigators across the country with world leading expertise in state-of-the-art trial design and execution of multisite studies. The JHU-Tufts TIC is one of three TICs nationally that will provide a framework for excellence in clinical trial practice to allow new treatments and drugs to reach patients faster and in a more cost effective manner.  The TICs, at JHU-Tufts, Utah and Duke-Vanderbilt, along with a Recruitment Innovation Center (RIC) at Vanderbilt, and the 64 CTSA Program Hubs make up the NCATS Trial Innovation Network which will support investigators with protocol development, implementing central institutional review boards (IRBs) and recruitment plans while also developing and disseminating sustainable innovative practices across the network.

The Trial Innovation Network has established a new model of collaboration in multisite clinical trials by linking local resources at the 64 national NIH-supported CTSA Hubs and their more than 500 affiliated clinical institutions spanning all domains of healthcare, with the centralized expertise at the TICs and RICs. This will ultimately transform how clinical trials are conducted.

The JHU-Tufts TIC will lead two innovation projects; 1) the development and implementation of clinical trial performance metrics, and 2) novel trial design such as ‘efficacy to effectiveness’ (E2E) to generate evidence for optimal use of new treatments.

The JHU-Tufts TIC will be jointly led by principal investigators from both institutions, Harry P Selker, MD, Executive Director of ICRHPS and Dean of the Tufts CTSI at Tufts University, Daniel F. Hanley, MD the Jeffrey and Harriet Legum Professor of Neurology and Director of BIOS, and Daniel Ford, MD, MPH, the David M Levine Professor of Medicine and Vice Dean for Clinical Research in the Johns Hopkins School of Medicine.

Tufts Medical Center, led by researchers at the CCHRPS is one of 15 ‘Hub’ sites in a new national emergency medicine clinical trials network. The NIH-sponsored national SIREN Network will develop and conduct large-scale clinical trials to test new treatments in areas such as traumatic brain injuries, seizures, spinal cord injuries, cardiac arrest, heart attacks, congestive heart failure, pulmonary embolism, blood transfusion, and more.

The SIREN Network is an NIH cooperative five year award that will nationally bring together 15 ‘Hub’ institutions and their local ‘spoke’ sites, to provide a national infrastructure for conducting large multi-site clinical trials.

Tufts Medical Center, together with partners from the Tufts Medical Center Clinical and Translational Science Institute (CTSI), Clinical Research Network (Maine Medical Center, Central Maine Medical Center, Eastern Maine Medical Center, Baystate Medical Center, and Lahey Hospital and Medical Center), form the Tufts SIREN Hub and Spokes and will act as a coordinated network to develop and execute emergency medicine trials. The Tufts CTSI Clinical Research Network encompasses an urban quaternary care academic health center and large community-based hospitals in urban, suburban and rural areas, a mix that reflects much of the range of the 5,000-plus hospitals in the US, allowing for greater generalizability of research findings to clinical practice.

For more information read our press release.

The IMMEDIATE Trial, funded by the National Heart, Lung and Blood Institute (NHLBI) from 2006-2011, was a clinical effectiveness, multisite randomized control trial to assess the use of glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS). This was the first double-blind placebo controlled study of GIK for ACS, and the first to assess the use of GIK in the pre-hospital setting as administered by paramedics. The IMMEDIATE Trial demonstrated that very early administration of GIK by emergency medicine services (EMS) personnel reduced the incidence of cardiac arrest or mortality by 50% for individuals with ACS, and by 60% for those with a more severe form of myocardial infarction known as STEMI (ST-elevation myocardial infarction).

The IMMEDIATE Trial used ACI-TIPI and TPI predictive instruments, embedded into electrocardiographs to help to maximize identification of eligible participants in the pre-hospital setting by paramedics. While the results of the IMMEDIATE Trial were very encouraging, because prior GIK studies had not been positive - even though they gave GIK later than would be expected to work and had not been double-blind placebo studies such as IMMEDIATE, FDA has requested a confirmatory trial (IMEMDIATE-2).

The IMMEDIATE-2 Trial design is very similar to the original IMMEDIATE Trial with some notable exceptions. Firstly, enrollment will take place in both the Emergency Department (ED) and EMS settings, as opposed to only EMS settings for the IMMEDIATE Trial. This more accurately reflects the typical clinical distribution of patients with ACS, where up to 50% come directly to the ED and will help to increase the opportunities for enrollment. Secondly, the primary endpoint will be a Finkelstein-Schoenfeld hierarchical endpoint of the combination of all-cause 30-day mortality, in-hospital cardiac arrest, and infarct size.

IMMEDIATE-2 is anticipated to begin Q3 2018 and will enroll 1,600 participants.

IMMEDIATE Trial Publications

Study Design for the Immediate Myocardial metabolic Enhancement during Initial Assessment and treatment in Emergency Care (IMMEDIATE) Trial

Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients with suspected acute coronary syndromes

To read more of our IMMEDIATE publications, visit our site.

Efficacy to Effectiveness (E2E) is an approach to clinical trial design that addresses the effectiveness and safety gaps that often occur in standard randomized controlled trials. E2E Trials are designed prospectively, whereby an effectiveness trial would commence seamlessly upon completion of the efficacy trial. This approach offers an opportunity for improved understanding of how a treatment will work in more usual real-world clinical settings.

Reasons for adopting an E2E Trial Design:   

• To provide a broader understanding of the treatment
• To allow understanding heterogeneity of treatment effects for special patient groups
• Greater evidence for physicians, payers, providers and patients.
• Better translation of research results into an impact on the public
• Potential for wider target population

The JHU-Tufts Trial Innovation Center (JHU-Tufts TIC) want to work with interested CTSA investigators nationally to develop the E2E concept and understand the challenges and potential solutions for better linking efficacy and effectiveness trials. Through consultations and workshops we will work with investigators to design the logistics and features of a specific intervention, including site selection, inclusion and exclusion criteria, data issues, engagement of industry, and regulatory matters related to approval for marketing.

The team working on this project includes highly experienced comparative effectiveness researchers, trialists, clinical epidemiologists, statisticians, pharmacologists, and experts in drug development and testing, from academics, industry, and the FDA.

The JHU-Tufts TIC, in collaboration with MIT’s NEWDIGS program is hosting a series of Design Labs, the next of which will take place in May 2018 in Boston. This interactive multi-stakeholder event will provide a venue to discuss the considerations and challenges of designing a Phase 2 or Phase 3 E2E multi-site clinical trial that supports the generation of robust efficacy and effectiveness data. These DesignLabs are an opportunity to bring together physicians, payers, industry, regulatory agencies and patient groups for structured and open conversation under strict confidentiality agreements. One of the earliest projects that the NEWDIGS team helped bring to fruition was adaptive licensing, which is now part of the regulatory pathway in Europe.

For more information on NEWDIGS, visit their website. 

Investigators are invited to apply for an Initial Consultation at the Trial Innovation Network website here

Read more about E2E here:

Integrated Efficacy to Effectiveness Trials

Nature of E2E Clinical Trials

Effifacy to Effectiveness Clinical Trial Design: Generating Evidence for Optimal Use of New Treatments
Listen to the webinar.

The JHU-TIC, in collaboration with the Tufts Center for the Study of Drug Development (CSDD) are leading a project to define a set of common, generalizable trial performance metrics and associated benchmark values.

Using both prospective landscape scan and retrospective regression analysis, we will identify a set of metrics that are predictive of specific performance outcome measures. These metrics will be developed and disseminated within the Trial Innovation Network to allow sites to measure and improve performance.

Training materials outlining metric collection and analysis, operational guidelines for each metric will be developed, prior to a pilot of these metrics in the Tufts MC CTSI Clinical Research Network.

The JHU-Tufts team will work closely with the CTSA Common Metrics Initiative as they roll out the new Accrual Metric. JHU and Tufts are two of the sites included in the Accrual pilot.

More updates will be posted here as the project progresses.

Harry P. Selker, MD, MSPH
Director, CCHSR and Professor of Medicine

Denise Daudelin, RN, MPH
Assistant Professor of Medicine 

Dorothy Dulko, PhD
Project Director

Manlik Kwong, BSEE, BSCS
Instructor of Medicine

Marisha Palm, MSc, PhD
Assistant Professor, Program Director

Cortney Wieber, MS
Senior Project Manager