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By Joan Korth-Bradley

Korth Bradley-finalThe successful registration of a new drug requires completion of at least two randomized, controlled clinical trials demonstrating safety and efficacy in the intended patient population. The successful integration of a new drug product into clinical practice requires much more! Prescribers need information that will help them treat real life patients who may be more complicated than those who participated in the clinical trials. Translational research provides the answers.

If you were asked to describe the concept of translational research, how would you respond? Minna and Gazdar defined it as the process of translating discoveries made in a laboratory into clinical interventions with a direct benefit to human health. However, there has been frustration on the part of researchers and clinicians about the difficulty encountered in applying information learned in laboratories to the clinical care of patients. There are so many unmet medical needs; surely somewhere in the new knowledge about pharmacogenomics and methods to harness big data, among other advances, are the answers we seek.

The Clinical Research Roundtable of the Institute of Medicine conducted a comprehensive assessment of translational research and identified two roadblocks to moving new knowledge into clinical practice. The first is situated between basic biomedical research and clinical science (T1) and the second between clinical science and knowledge and improved health (T2). The causes of the blocks included lack of willing participants, regulatory burden, fragmented infrastructure, incompatible databases, career disincentives, practice limitations, high cost, and lack of dedicated funding. While current conditions are not perfect, progress has been made in the two decades since these observations were made. The National Institutes of Health (NIH), among others, have made translational research a priority among its institutes. It also acknowledged that an improvement in translation from controlled, observational human clinical research to clinical practice was needed.

Clinical pharmacology is the science of understanding the mechanism of action, pharmacokinetics (PK), and pharmacodynamics (PD) of medications in clinical settings. PK/PD questions answered by T2 studies provide information important to subsequent clinical trials as well as patient care, such as the impact on drug absorption of food or the coadministration of commonly prescribed medications. The meaning of the first two letters of the CPTR section, where the scientists working in this portion of drug development typically join the American Association of Pharmaceutical Scientists (AAPS), is clear—Clinical Pharmacology, but what about the last two letters, Translational Research (TR)? When assessed through the lens of the definitions above, many of the conventional clinical pharmacology studies that explore the impact of intrinsic and extrinsic factors on the pharmacokinetics of medications are T2 translational research studies, as are larger phase 2 and 3 clinical studies, pharmacoepidemiology studies, and postapproval studies conducted to further optimize the use of pharmacotherapy in patient care.

In the cover article in the December issue of the AAPS Newsmagazine, several key studies in the development of etanercept provide examples of T2 translational research and demonstrate the effectiveness of such research in improving actual clinical benefit. Read T2 Translational Research in Clinical Development: A Case Study, from the CPTR section, and then participate in the discussion point below.

What are notable examples of translation of clinical research results into personalization of patient care?

Joan Korth-Bradley is senior director, clinical pharmacology lead, at Pfizer Inc., in Collegeville, PA. She is active in conduct of T2 translational research in support of optimizing pharmacotherapy in hemophilia and other rare diseases.