Clinical Research Advances: PROMIS, PCORI, and ADME-Tox
This paper examines two key areas of contemporary clinical research: advances in patient-reported outcomes measurement and preclinical drug development. The first section reviews the NIH's PROMIS initiative and PCORI's $102 million funding expansion, including a study by Doll et al. (2014) on quality of life outcomes in patients with gynecologic cancer and obesity. The second section explores preclinical drug development, focusing on ADME-Tox assays, in vitro cell culture techniques, hepatocyte models, and the hERG assay, all of which aim to improve the predictive accuracy of preclinical studies and reduce costly drug failures in later clinical trials.
- Advances in Clinical Research and Patient-Centered Outcomes: NIH PROMIS initiative and patient outcome measurement goals
- PCORI Funding and Obesity Research: PCORI awards $102 million for clinical effectiveness research
- Quality of Life in Gynecologic Cancer and Obesity: NCI-funded study links obesity to worse QOL outcomes
- Preclinical Drug Development and ADME-Tox Assays: ADME-Tox methods improve drug safety and efficacy prediction
- Animal Studies and Toxicokinetics in Preclinical Research: Animal toxicokinetic studies establish safe human dosage ranges
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What makes this paper effective
- The paper integrates real funding figures, named programs, and specific study citations (Doll et al., 2014; Glaser, 2007) to ground its claims in concrete evidence rather than general assertions.
- It clearly connects macro-level policy developments (PROMIS, PCORI funding) to specific micro-level research findings, demonstrating how institutional investment translates into clinical knowledge.
- The preclinical section moves logically from absorption to metabolism to toxicity, reflecting the actual sequence of ADME-Tox evaluation and making the technical content easy to follow.
Key academic technique demonstrated
The paper demonstrates effective synthesis of primary research findings with policy and funding context. Rather than summarizing sources in isolation, the author connects the Doll et al. (2014) study to the PROMIS initiative's goals, showing how the study's findings validate broader institutional priorities. This integrative approach is a hallmark of graduate-level literature engagement.
Structure breakdown
The paper is divided into two clearly labeled sections. The first, "Advances in Research," covers patient-centered outcomes measurement through PROMIS and PCORI, anchored by a specific clinical study on cancer and obesity. The second, "Preclinical Development," addresses drug pipeline challenges and the role of ADME-Tox technologies, moving from in vitro assays to animal toxicokinetic studies. Each section is largely self-contained but shares the underlying theme of improving the clinical research pipeline.
Advances in Clinical Research and Patient-Centered Outcomes
The Common Fund programs of the National Institutes of Health (NIH) include the PROMIS (Patient-Reported Outcomes Measurement Information System) initiative (NIH, 2013). The PROMIS initiative seeks to exploit the creative potential of researchers and clinicians for the purpose of developing new methods for reporting patient outcomes. In contrast to more quantitative measures such as laboratory tests and radiological findings, the PROMIS initiative is focused on outcomes from the perspective of patients. These outcomes can include patient reports of changes in pain levels, activities of daily living, cognitive performance, social connectedness, and psychological health. These outcome measures will be used to inform researchers and clinicians about an intervention's effectiveness from a relevant and potentially more meaningful perspective.
PCORI Funding and Obesity Research
Passage of the 2010 Patient Protection and Affordable Care Act provided funds for the creation of the Patient-Centered Outcomes Research Institute (PCORI), a non-profit institute dedicated to improving the quality and relevance of the evidence used for making evidence-based healthcare decisions (PCORI, 2014). Recently, PCORI announced funding for 46 new research projects totaling $102 million for clinical effectiveness research (CER) projects (PR Newswire, 2014). This amount is in addition to the $671 million in awards that have been made since PCORI began funding research projects in 2012. The main focus of the most recent funding decision is patient-centered outcomes in obesity and patient transitions from hospital to home. The Addressing Disparities Program will award two $10 million grants for studying obesity treatments offered in the primary care setting, while the Healthcare Systems Program will award almost $15 million to help identify services that benefit patients the most when transitioning from hospital to home. In addition, eight awards incorporating the goals of the PROMIS initiative have been made available.
Preclinical Drug Development and ADME-Tox Assays
As Glaser (2007) notes, Big Pharma has suffered repeatedly after promising new drugs turned out to have safety and efficacy shortcomings in clinical trials. The resulting injury to patients and loss of untold millions in research and development dollars has fueled efforts to reimagine the optimal bench-to-bedside pipeline. Currently, the drug pipeline takes anywhere from 5 to 12 years and can cost $800 million with no assurance of success. If researchers could develop preclinical methods that would minimize the safety and efficacy risks associated with novel drugs earlier in the pipeline, both patients and the pharmaceutical industry would benefit. Of primary concern, according to Glaser (2007), are bioavailability, pharmacokinetics, and toxicity — although the latter is widely considered the primary reason for drug failures after pharmacokinetics was shifted to earlier stages of the drug development process.
Among the preclinical technologies receiving attention are Absorption, Distribution, Metabolism, and Excretion Toxicity (ADME-Tox) assays (Glaser, 2007). Absorption is similar to bioavailability because it is concerned with the ability of an orally administered drug to cross the intestinal epithelium (Guttendorf, 2011). Cell and tissue culture techniques have been developed to facilitate absorption studies of a candidate drug. The value of in vitro absorption findings is limited, however, by the extent to which a drug can be utilized once it has crossed into the circulatory system. Although valuable insights concerning a drug's absorption activity can be gleaned from a careful analysis of chemical structure, in vitro cell culture assays remain essential. An analysis of chemical structure can also be informative regarding a drug's metabolic profile; however, the use of hepatocyte cultures remains the preferred tool. Cultured hepatocytes and hepatic tissue slices retain many of the enzymatic activities that would be observed in vivo, thereby providing valuable insights into a drug's metabolic profile. Among those techniques gaining both industry and regulatory acceptance is the hERG (human Ether-à-go-go-Related Gene) assay, because this gene produces a potassium channel known to be involved in long QT syndrome and sudden cardiac arrest (Glaser, 2007). Any interaction with the potassium channel would likely be considered fatal to a drug's development. The general experimental approach across all these techniques is to test the toxicity of a candidate drug using multiple cell lines while measuring multiple variables. The overall goal is to make preclinical studies more predictive of a drug's behavior once it has been introduced into a living human.
References
Doll, K. M., Kalinowski, A. K., Snavely, A. C., Irwin, D. E., Bensen, J. T., Bae-Jump, V. L., et al. (2014). Obesity is associated with worse quality of life in women with gynecologic malignancies: An opportunity to improve patient-centered outcomes. Cancer, published online ahead of print 23 Sep. 2014. doi:10.1002/cncr.29061
Glaser, V. (2007, May 1). Building better pipelines with ADME-Tox: Advances in microdosing, in vitro analysis, and biosimulation for optimized predictive studies. Genetic Engineering & Biotechnology News, 27(9).
Guttendorf, R. J. (2011). The emerging role of A.D.M.E. in optimizing drug discovery and design. Retrieved from http://www.netsci.org/Science/Special/feature06.html
NIH. (2013). PROMIS: Patient-Reported Outcomes Measurement Information System: Overview. Retrieved from http://commonfund.nih.gov/promis/overview
PCORI. (2014). About us. Retrieved from http://www.pcori.org/about-us
PR Newswire. (2014, September 30). PCORI board approves $102 million in support for 46 new research projects. Retrieved from
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