All posts by Gina Uhlenbrauck

Study Design Improvements Have Positive Effects on Trial Performance

A recent impact report from the Tufts Center for the Study of Drug Development details how efforts to streamline clinical trial design appear to be yielding results [1]. Industry trial sponsors are using mechanisms such as facilitated review processes and adaptive trial designs to identify and address study feasibility issues, thereby reducing trial costs and administrative burden.

The center reviewed more than 20,000 procedures from recent phase 2 and 3 trials sponsored by 8 major pharmaceutical or biotechnology companies and conducted a survey with 83 industry executive respondents on experience with facilitated review processes.

Highlights from the analyses include the following:

  • 21% of procedures in phase 2 trials and 31% in phase 3 trials were for “non-core” data that did not support primary or key secondary outcomes
  • Non-core procedures accounted for, on average, one-quarter of a study budget
  • >90% of non-core data collected were included in clinical study reports and regulatory submissions
  • 21% of companies reported using simple adaptive trial designs to reduce costs and improve chances of study success; <10% reported using sophisticated adaptive designs
  • 76% of surveyed companies reported using facilitated review processes within the past 5 years
  • Many companies reported modest to major improvements in various measures of trial performance since implementing facilitated review processes (figure)
Figure: Percentage of companies reporting modest to major improvement in trial performance measures since implementing facilitated review processesPercentage of companies reporting modest to major improvement in trial performance measures since implementing facilitated review processes [1].

A discussion of social media perceptions with 20 pharmaceutical and biotechnology companies, as detailed in the report, further revealed that companies see potential value in soliciting stakeholder (e.g., investigators, patients) input on study design via social media. However, serious concerns regarding lack of regulatory guidance and potential for bias have kept companies from implementing this type of engagement to date.


1. Tufts Center for the Study of Drug Development. Protocol design optimization starting to improve study performance. Tufts CSDD Impact Report. 2014;16(5).

Interdisciplinary Group Outlines Research Agenda for Realizing National-Scale Learning Health System

An article published online this month in the Journal of the American Medical Informatics Association (JAMIA) outlines research challenges that must be addressed to achieve a high-functioning learning health system (LHS) that uses data to generate knowledge and improve care in continuous cycles. The article, titled “Toward a Science of Learning Systems: A Research Agenda for the High-Functioning Learning Health System,” is the product of an international workshop sponsored by the National Science Foundation. The workshop involved 45 prominent interdisciplinary researchers, who examined use cases for a national-scale LHS to determine a path toward this goal.

“…the LHS can succeed only by creating novel combinations of role, process and technology. This must occur by working back from the future, not by figuring out how to fix the various problems with a current system that fails to learn rapidly, routinely, and at scale.”

The group synthesized a research agenda in the form of key questions targeted at four system-level requirements for a high-functioning LHS. The authors further propose that addressing these questions will involve evolution to a new interdisciplinary science of “cyber-social ecosystems” in which diverse stakeholders collaborate to drive innovation.

Additional information from the workshop, including participants, slides, and use cases, is available online.

Article authors include NIH Collaboratory Coordinating Center Co-Principal Investigator Richard Platt, MD, MSc, and Co-Chair of the NIH Collaboratory Electronic Health Records Core, Jeffrey Brown, PhD.

New IOM Report on Integrating Research and Practice

The Institute of Medicine (IOM) has released a new report, Integrating Research and Practice: Health System Leaders Working Toward High-Value Care: Workshop Summary. The report summarizes the presentations and discussions from two meetings held in April and June 2014 by the IOM’s Roundtable on Value & Science-Driven Health Care, with sponsorship from the Patient-Centered Outcomes Research Institute (PCORI).

The workshops brought together health system leaders and researchers to discuss partnerships for progress toward a learning healthcare system in which the continuous generation of knowledge informs better care. Attendees identified challenges and established priorities in integrating clinical research into healthcare delivery systems. There was a particular focus on the recently established National Patient-Centered Clinical Research Network (PCORnet).

View the Workshop Summary
(Note: The workshop summary contains the opinions of the workshop presenters and does not reflect conclusions of the IOM.)

PCORI Executive Director Dr. Joe Selby to Speak on Regulatory Issues Concerning Big Data

The meeting of the Secretary’s Advisory Committee for Human Research Protections (SACHRP) scheduled for July 21-22, 2014, will include a session on “Regulatory Issues Concerning Big Data.” Joe Selby, MD, MPH, executive director of the Patient-Centered Outcomes Research Institute (PCORI), will speak, along with leaders from the NIH and FDA. The session is scheduled for 1:30-3:45 pm on Monday, July 21.

SACHRP provides recommendations on human subjects protection to the Secretary of the U.S. Department of Health and Human Services and reviews activities of the Office for Human Research Protections (OHRP). Other topics to be covered during the two-day meeting include informed consent comprehension, the return of research results to human subjects, and ethical/regulatory issues in interventional social media research.

The meeting is available to the public and will be videocast live.

View the meeting agenda
View the live webcast (available July 21-22, 2014)

A link to materials from the meeting will be provided in an update to this post when available.

New Living Textbook Chapter – Electronic Health Records-Based Phenotyping

A new Living Textbook topic chapter, “Electronic Health Records-Based Phenotyping,” has just been published. The chapter defines computable phenotypes and describes their role in data queries of electronic health records as part of pragmatic clinical trials. A main focus of the chapter is outlining mechanisms for identifying and evaluating phenotype definitions, with particular emphasis on standardization efforts of the NIH Collaboratory, including the Table 1 Project. Also included are links to recommended phenotype definitions from the Collaboratory Phenotypes, Data Standards, and Data Quality Core.

Dr. Califf to Speak Today at NIH Common Fund 10-Year Commemoration Symposium

On June 19, 2014, the NIH Common Fund is celebrating 10 years of achievement with a symposium, A Decade of Discovery, featuring its far-reaching research. Dr. Robert Califf, principal investigator of the NIH Collaboratory Coordinating Center, will speak during the 2:15-3:15 pm session “Reengineering the Clinical Research Enterprise.” Proceedings will be streamed live throughout the day.

View the agenda, live videocast, and commemorative book

Winners from the video and song contest will also be recognized.

“Diagnosis: Data” Series Chronicles Applications of Healthcare Data in Camden, NJ

A series aired on American Public Media’s Marketplace program profiled real-world examples of using healthcare data to improve care and reduce costs in Camden, NJ.

1. Using data to treat the sickest and most expensive patients
2. Data: The secret ingredient in hospital cooperation
3. Data opens doors in healthcare, but then what?
Image of Jeffrey Brenner, MD
Jeffrey Brenner, MD. Courtesy: MacArthur Foundation.

The first segment follows Dr. Jeffrey Brenner, a MacArthur award–winning family physician who is conducting a randomized controlled trial of a care program targeted at healthcare “superutilizers”—patients with chronic conditions who accumulate high numbers of hospital visits and associated costs. The second story highlights how hospitals in Camden have created a health information exchange to share data for their Medicaid patients, with the goal of providing better care and preventing waste associated with duplicate tests. Interviewees explain that despite the potential benefits, hospitals have traditionally been reluctant to share data, but this position may be changed by incentives. The final program demonstrates that data can only go so far, sometimes revealing challenges that are not easily addressed.

“Diagnosis: Data” was produced in collaboration with Healthy States as part of reporting work examining changes in healthcare in the wake of the Affordable Care Act.

Developing Approaches to Conducting Randomized Trials Using Mini-Sentinel: Webinar and White Paper

A recent webinar (see recording) covered a collaborative effort of the Clinical Trials Transformation Initiative (CTTI) and the FDA Mini-Sentinel project in which investigators are exploring the possibility of using the Mini-Sentinel distributed database infrastructure to conduct randomized, multicenter clinical trials. Speakers Richard Platt, MD, MS, of Harvard Pilgrim Health Care Institute, and Patrick Archdeacon, MD, of the FDA, summarized the work and discussed next steps that will continue to advance the project.

A white paper published earlier this year, Developing Approaches to Conducting Randomized Trials Using the Mini-Sentinel Distributed Database, describes the results of the investigator analysis in greater detail. The white paper is the product of the CTTI Uses of Electronic Data project.

PCORnet: “Not your father’s clinical trial network”

“PCORnet: Turning a Dream Into Reality,” an editorial published online this week in the Journal of the American Medical Informatics Association, details the promises of the National Patient-Centered Clinical Research Network (PCORnet):

“Providing accurate answers based on the highest levels of scientific evidence for the majority of unresolved clinical questions is a revolutionary dream shared by patients, providers, payers, health plans, researchers, and policy makers alike. PCORnet, the National Patient-Centered Clinical Research Network, promises a transformative platform that will turn this revolutionary dream into reality.”

The authors describe PCORnet’s patient-centered vision and how its transformative clinical research will be carried out through a national research network involving both Clinical Data Research Networks and Patient-Powered Research Networks. This “network of networks” is designed to include a large, highly representative population. PCORnet will first work to establish data architecture and standards and address key policy questions, followed by the conduct of its first pragmatic clinical trial slated to begin in September 2015.

Editorial authors include NIH Director Dr. Francis Collins and PCORnet Steering Committee members Kathy L. Hudson, PhD, and Josephine P. Briggs, MD.

NIH Announces New Policies to Mandate Inclusion of Female Cells and Animals in Preclinical Research

In a commentary published this week in the journal Nature and featured in the New York Times, NIH Director Dr. Francis Collins unveiled new NIH policies that will require balanced inclusion of male and female cells and animals in NIH-funded preclinical research (with few defined exceptions). Though inclusion of women in NIH-funded clinical trials has improved to the point where about half of all research participants are women, preclinical research lags in achieving a sex balance. One reason cited for the continued predominance of male models in preclinical research is researchers’ concerns about effects of the estrous cycle on research findings; however, the current situation may also simply reflect the inertia of years of laboratory conventions. Described as a “blind spot” in preclinical research, the lack of adequate inclusion of female models is troubling, given the numerous examples of sex differences in areas including cell physiology, drug metabolism, and adverse drug effects.

“Inadequate inclusion of female cells and animals in experiments and inadequate analysis of data by sex may well contribute to the troubling rise of irreproducibility in preclinical biomedical research, which the NIH is now actively working to address.”

The new NIH policies will begin with a staggered rollout starting in October 2014. The policies will be supplemented by other NIH efforts such as training, partnerships with publishers to encourage publication of sex analyses, and a program launched in 2013 that extends supplemental funding to existing research to increase sex comparisons.

The Nature commentary was co-authored by Janine A. Clayton, MD, director of the Office of Research on Women’s Health and associate director for Research on Women’s Health for the NIH.