Research Publications

CDEK: Clinical Drug Experience Knowledgebase

Database (Oxford). 2019 Jan 1;2019:baz087. doi: 10.1093/database/baz087.

The Clinical Drug Experience Knowledgebase (CDEK) is a database and web platform of active pharmaceutical ingredients with evidence of clinical testing as well as the organizations involved in their research and development. CDEK was curated by disambiguating intervention and organization names from ClinicalTrials.gov and cross-referencing these entries with other prominent drug databases. Approximately 43% of active pharmaceutical ingredients in the CDEK database were sourced from ClinicalTrials.gov and cannot be found in any other prominent compound-oriented database. The contents of CDEK are structured around three pillars: active pharmaceutical ingredients (n = 22 292), clinical trials (n = 127 223) and organizations (n = 24 728). The envisioned use of the CDEK is to support the investigation of many aspects of drug development, including discovery, repurposing opportunities, chemo- and bio-informatics, clinical and translational research and regulatory sciences.

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2018 in review: FDA approvals of new molecular entities

2018 was a remarkable year, both in terms of the number of new molecular entities (NMEs) approved and the organizations developing them. In total, 59 NMEs received a nod from the US Food and Drug Administration (FDA), most of which were approved using a priority or breakthrough designation. Orphan drugs accounted for more than half of new approvals, only the second time in history that level has been achieved. Moreover, the net number of organizations that received an FDA approval and remain active in new drug research surged in 2018, reflecting both an increase in new organizations and lower levels of industry consolidation.

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Assessing the public landscape of clinical-stage pharmaceuticals through freely available online databases

Drug Discov Today. 2019 Apr;24(4):1010-1016. doi: 10.1016/j.drudis.2019.01.010. Epub 2019 Jan 25. PMID: 30690196

Several public databases have emerged over the past decade to enable chemo- and bio-informatics research in the field of drug development. To a naive observer, as well as many seasoned professionals, the differences among many drug databases are unclear. We assessed the availability of all pharmaceuticals with evidence of clinical testing (i.e., been in at least a Phase I clinical trial) and highlight the major differences and similarities between public databases containing clinically tested pharmaceuticals. We review a selection of the most recent and prominent databases including: ChEMBL, CRIB NME, DrugBank, DrugCentral, PubChem, repoDB, SuperDrug2 and WITHDRAWN, and found that $11 700 unique active pharmaceutical ingredients are available in the public domain, with evidence of clinical testing.

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Lost medicines: a longer view of the pharmaceutical industry with the potential to reinvigorate discovery.

Kinch MS, Kinch GA, Griesenauer RH. Drug Discov Today. 2018 Sep 14. pii: S1359-6446(18)30266-6. doi: 10.1016/j.drudis.2018.09.006

It is widely understood that the 1962 Kefauver-Harris Amendment to the Food, Drug and Cosmetics Act ushered in the modern regulation of medicines requiring a combination of safety and efficacy. However, fewer appreciate the amendment was applied retroactively to virtually all medicines sold in the USA. For various reasons, many medicines faded into history. Here, we identify and analyze >1600 medicines (including over-the-counter drugs) and their innovators prior to the enactment of Kefauver-Harris.

We report 880 of these past medicines are no longer accessible. This project also reveals new insight into the pharmaceutical enterprise, which reveals an industry already mature and beginning to retract before enactment of the legislation. Beyond its historical implications, the recollection of these medicines could offer potential starting points for the future development of much-needed drugs.

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2017 in review: FDA approvals of new molecular entities

Kinch MS, Griesenauer RH. Drug Discov Today. 2018 Aug;23(8):1469-1473. doi: 10.1016/j.drudis.2018.05.011. Epub 2018 May 8.

An overview of drugs approved by the FDA in 2017 reflected a reversion to the mean after a low number of NME approvals in 2016. This reversal was largely driven by the largest number of biologics-based NMEs recorded to date, which offset an average number of small-molecule approvals. Oncology indications continued to dominate followed by novel treatments for infectious, immunologic and neurologic diseases. From a mechanistic standpoint, the industry has continued a trend of target diversification, reflecting advances in scientific understanding of disease processes. Finally, 2017 continued a period of relatively few mergers and acquisitions, which broke a more-than-a-decade-long decline in the number of organizations contributing to research and development.

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An overview of FDA-approved vaccines & their innovators.

Griesenauer RH, Kinch MS. Expert Rev Vaccines. 2017 Dec;16(12):1253-1266. doi: 10.1080/14760584.2017.1383159. Epub 2017 Sep 25.

A survey of FDA-approved biologicals focused upon the development of immunotherapies over time to gain insight on the challenges and trends of vaccine development today. Areas covered: A total of 135 different immune-based therapies were broadly divided into passive or active immunotherapies. Whereas just over half of passive immunotherapies targeted infectious diseases, the vast majority of active immunotherapy products (vaccines) were directed against a handful of viral and bacterial pathogens. We also analyze changes in vaccine strategy, including the use of viable antigens and subunit approaches. Expert commentary: An analysis of vaccine innovators revealed an ever-increasing presence of the private sector and a relatively diminishing role for the public sector . Whereas North American companies have contributed to the approval of two-thirds of vaccines, European companies have regained parity in terms of hosting innovators of vaccine research and development.

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2016 in review: FDA approvals of new molecular entities.

Griesenauer RH, Kinch MS. Drug Discov Today. 2017 Nov;22(11):1593-1597. doi: 10.1016/j.drudis.2017.06.011. Epub 2017 Jul 4.

An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of mergers and acquisitions decreased the total number of organizations with past approval experience and continued research and development (R&D) activities to 102, divided evenly between more established pharmaceutical and newer biotechnology companies. Despite these substantial differences, the industry continued to pursue regulatory incentives, as evidenced by a continued increase in the fraction of NMEs approved using an orphan or priority designation, and almost all oncology drugs approved in 2016 utilized these mechanisms.

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NIH Support for FDA-Approved Medicines

Griesenauer RH, Moore R, Kinch MS. Cell Chem Biol. 2017 Nov 16;24(11):1315-1316. doi: 10.1016/j.chembiol.2017.11.002. A recent budget proposal from the current American administration has compelled discussions about Federal funding for the introduction of new medicines (Reardon et al., 2017). While the funding allocated to the National Cancer Institute and the Office of the Director did increase from FY16 to FY17 (though no other institute changed), the President has proposed an 18% cut to funding moving forward (Achenbach and Sun, 2017, US Department of Health & Human Services, 2017). These conversations prompted an analysis of the impact of National Institutes for Health (NIH) funding for innovative Food and Drug Administration (FDA) drug approvals (hereafter referred to as New Molecular Entities or NMEs).
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Analysis of FDA-approved imaging agents.

Kinch MS, Woodard PK. Drug Discov Today. 2017 Jul;22(7):1077-1083. doi: 10.1016/j.drudis.2017.03.006. Epub 2017 Mar 21.

The development of imaging agents was initially driven following the discovery of X-ray technologies, but quickly evolved and expanded to include radiolabeling of cells and tissues to assist disease diagnosis and progression. The first imaging agents preceded the Great War but the field did not gain momentum until the 1950s. The approval rate for imaging NMEs continued at a high level for the remainder of the 20th century, but substantially decreased thereafter. This decline in approval rates corresponds with industry consolidation. Such losses have stabilized, but could have important implications for a field that has conveyed direct benefits to medicine and that could ensure the future of the wider biopharmaceutical industry.

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Food and microbiota in the FDA regulatory framework.

Green JM, Barratt MJ, Kinch M, Gordon JI. Science. 2017 Jul 7;357(6346):39-40. doi: 10.1126/science.aan0836. No abstract available.
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