The National Heart, Lung, and Blood Institute (NHLBI) has established the Innovative Clinical Trials Resource (ICTR) program to provide infrastructure and expertise to support awardees of the NHLBI “Catalyzing Innovation in Late Phase Clinical Trial Design and Statistical Analysis Plans Initiative” (U34/X01). The U34/X01 initiative will provide funding support for planning activities for late phase (phase II and beyond) single-site or multi-site investigator-initiated clinical trials (see NOT-OD-15-015 for NIH clinical trial definition) that address critical clinical questions within the mission of the NHLBI. Applicants to the U34 and X01 Funding Opportunity Announcements (FOAs) will propose a late phase clinical trial (Phase II and beyond) to address a priority research question in heart, lung, blood, or sleep (HLBS) science that require a non-standard rather than a traditional design because a randomized controlled approach to the study question is inadequate, limited, or suboptimal with the opportunity for statistical novelty and/or innovation.

 

Clinical trials are a key strategy used by the NHLBI to improve prevention, diagnosis, and treatment of heart, lung, blood, and sleep disorders. Clinical trials also represent a significant investment of human and material resources. Effective planning, oversight, and high standards for the safe, timely, and efficient conduct of clinical trials are integral to maximizing their scientific impact and return on investment. For the majority of clinical trials, traditional designs adequately power the statistical analysis plan. Some key features of traditional clinical trial designs are subject randomization, blinding (masking) of subjects and researchers to the study intervention(s), the use of a control comparison group, and a classic intent-to-treat analysis.

 

However, as noted in the 2001 IOM Report on Small Clinical Trials, clinical trials conducted in limited populations may not be able to use traditional clinical trial designs to achieve adequate statistical power, and that designing and planning trials using new innovative statistical design and analysis plans requires specific expertise that may be difficult to locate and access. Scientific areas identified across NHLBI, in which such trials might be required include, but are not limited to, studies of rare diseases and/or therapeutics in which sample size limitations provide a challenge to the statistical power of traditional randomized clinical trial designs; studies in sub-populations of more common diseases, e.g. precision medicine trials; and late-stage implementation research. Other examples could include trials for the study of interventions in a non-randomized study setting and clinical trials in which a meaningful or optimal treatment control arm may be difficult to implement.

 

In May, 2018, NHLBI awarded Berry Consultants a contract to provide services as the ICTR contractor. Berry Consultants will serve as a Statistical Consultative Resource for the Catalyzing Innovation in Late Phase Clinical Trial Design and Statistical Analysis Plans Initiative” (U34/X01) awardees to provide the necessary facilities and equipment, and the administrative, regulatory, IT and statistical expertise necessary to assist in developing novel/innovative clinical trial designs and appropriate statistical analysis plans. The ICTR contractor shall also provide guidance to the U34/X01 awardee on regulatory issues related to innovative late phase clinical trials and develop and provide an education program on the application of non-traditional clinical trial design and analysis of clinical trials targeted to the NHLBI research community.

 

Berry Consultant’s support as the ICTR contractor is not intended to replace the activities conducted by investigators developing their trials, but serves as a resource for expert scientific and statistical advice, review of protocols and study materials, and training in areas relevant to the design or implementation of innovative clinical trials. The services provided might include:

  • clinical trial design and recruitment strategy studies in rare diseases and pediatrics
  • biostatistical support
  • site and subject recruitment strategies
  • regulatory issues
  • bioethics consultation
  • preparing clinical protocol, manual of procedures, training materials, consent forms and data safety monitoring plan
  • planning a multi-site clinical trial, including multiple-site IRB approval and contracting
  • preparation of agreements for industry collaborations
  • identifying and establishing collaborations
  • investigator-targeted education in clinical trials methodology
  • data capture and data management systems.

In addition, the ICTR infrastructure provides this web-based communication platform with a public environment that facilitates the training of any interested investigator on non-traditional clinical trial design and analysis.

To contact the ICTR Team, please email the Project Manager at Berry Consultants, Doray Sitko.