A Guide to Time Lag and Time Lag Shortening Strategies in Oncology-Based Drug Development

Transformation of a new scientific idea into a new oncology-based drug requires a tremendous amount of time, effort and investment. The initial, but critical first step in this process is transferring basic oncology research into a clinical application known as a “translational” or “bench to bedside study”. As a postdoctoral fellow who performs prostate cancer research related bench work, I have been asking how long my project might take to reach a patient as a cure rather than just becoming another scientific publication! I realize that for a cancer patient who has been waiting for a new drug treatment to survive, the time length that is required for drug development could actually cost the patient their life. From this point of view, the time length between bench work and a follow-on translational study (also called “time lag”) is critically important. Clearly the biggest problem is to ask and determine how it could be possible to decrease the time lag and allow potential benefits of a bench work to reach patients more quickly.
During my “Advanced Studies in Technology Transfer” program at the Foundation for Advanced Education in the Sciences (FAES) Graduate School at NIH, I worked to uncover answers for these questions as my Capstone Project.

The calculated “time lag” typically of 10 years for new oncology treatment
Before proposing solutions to shorten time lag in oncology drug development, I wanted to better define the “time lag” between bench work and translational study. For this purpose, I used the Pharmaprojects® database (produced by Citeline/Informa PLC), to follow the global clinical drug development from bench to patient and to calculate the time lag for the three most common cancer types: breast, lung and prostate cancer. 97 drugs were examined for time lag calculation for either breast, lung or prostate cancer. The time length between patent priority date and regulatory approval date was calculated for each drug. The average time required to launch a cancer drug was determined to be 11 years, 10 years and 10 years, respectively for breast, lung and prostate cancer.

What are the reasons for “time lag”?
To be able to uncover the reasons for a 10 year long time lag in cancer drug development, the key opinion leaders, including principal investigators, scientists, researchers from the National Cancer Institute (NCI), the National Center for Advancing Translational Sciences (NCATS), Yale University, Massachusetts Institute of Technology (MIT), Queen’s University School of Medicine, Dentistry and Biomedical Science, Belfast (U.K), and Regeneron Pharmaceuticals were interviewed, to formulate suggestions for helping new drugs reach from bench to bed side more quickly.

During these interviews, the following questions were discussed:

  1. How is it determined if basic research results are qualified to continue on for
    translation studies?
  2. What are the possible reasons for the lengthy time required to translate basic
    research into clinical practice?
  3. How could we shorten the time lag in biomedical research?

Scientific and Non-Scientific Reasons for Long “Time Lag”

For cancer patients, the10-year period to translate a new drug into clinical application is unfortunately more than a life time of delay. After interviews with many researchers, the reasons for a 10 year long “time lag” could be divided into two categories, scientific and non-scientific reasons. Problems in reproducible data generation, inappropriate use of in vitro/vivo models, and variation in human sample collection are classified as important scientific reasons. On the other hand, poor collaboration among industry and academia, problems in intellectual property (IP) sharing, ineffective public-private partnership due to lack of sharing of research tools are considered as non-scientific reasons.

Future Direction in Oncology-Based Drug Development: Collaboration, Collaboration and Collaboration!

One of the most common recommendations from all researchers whom I interviewed was the importance of collaboration. Most of the researchers think that collaboration should be considered as an inevitable requirement for all scientists to shorten the time lag, because “no one can do all by himself/herself”. This would encourage the application and use of differing expertise and points of views to support a steadier and more effective overall oncology research program.

Synergy between Academia and Industry

Researchers from both academia and industry also highlighted the importance of academia and industry partnership. Academic researchers have deep scientific knowledge, however they have been facing funding problems to pursue their research and utilize this basic knowledge. On the other hand, pharmaceutical companies generally have funding and applied skills, but they are often dependent on academia and small biotech companies for fundamental knowledge and novel discoveries. It is really a “relay race against time” for scientists from both academia and companies need to complete together in order to benefit oncology patient care. Therefore establishing a stronger and living connections between academia and pharmaceutical companies can create a shortcut and synergy to make to the journey from bench side to bedside quicker than ever before.

Repurposing of FDA Approved Drugs for Oncology Applications

For one of the interviews for this article, a principal investigator from a major university said that the time lag in bringing his research to market is only 2-3 years, because his laboratory studies FDA-approved drugs for different indications. Using FDA-approved drugs for other indications, or repurposing the drug, would dramatically reduce time lag and overall cost. The most exciting part of successfully repurposing drugs, of course, is that development of a drug into a new treatment for a patient’s benefit will be quicker.

About the Author
Berna Uygur is Postdoctoral Intramural Research Training Award Fellow at NICHD where she has been researching the role of cell fusion mediated cancer stem cell regeneration and drug resistance in prostate cancer microenvironment and she has been also researching extracellular vesicles mediated communication between prostate cancer cells. Prior to joining the NICHD, Berna received her PhD in Biochemistry and Molecular Biology from University of Maine, USA, where she studied “Regulatory Role of Slug Transcriptional Factor in Prostate Cancer”. She received her Master of Science degree in Applied Medical Science from University of Southern Maine, USA, where she studied “Toxicology of Silver Nanoparticles in Different Origins of Human Cells”. She received both her first Master of Science degree and Bachelor Science degree in Textile Chemistry Engineering from Ege University, Turkey. Berna is interested in translational science and technology transfer in biomedical research. She advanced her interest in technology transfer by completing the “Advanced Studies in Technology Transfer” program at the Foundation for Advanced Education in the Sciences (FAES) Graduate School at NIH. She has been pursuing her interest in translational science by attending NIH-Duke University Clinical Research Training Program at NIH.

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