Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015-2016

Moore, Thomas J.; Zhang, Hanzhe; Anderson, Gerard F.; Alexander, G. Caleb

doi:10.1001/jamainternmed.2018.3931

Cited by 252 publications

(214 citation statements)

References 8 publications

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“…Despite more than 60 years of experience, the drivers of VIKI are not yet fully understood 26 . Understanding VIKI in the clinical arena is challenged by the high cost of conducting clinical trials, which have been estimated to exceed a median of $40,000 per enrolled patient 27 . For drugs like vancomycin that are already approved and in use, this financial barrier relegates most investigations to retrospective study.…”

Section: Animal Models and Toxicodynamicsmentioning

confidence: 99%

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

et al. 2020

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Vancomycin is a recommended therapy in multiple national guidelines. Despite the common use, there is a poor understanding of the mechanistic drivers and potential modifiers of vancomycin-mediated kidney injury. In this review, historic and contemporary rates of vancomycin-induced kidney injury (VIKI) are described, and toxicodynamic models and mechanisms of toxicity from preclinical studies are reviewed. Aside from known clinical covariates that worsen VIKI, preclinical models have demonstrated that various factors impact VIKI, including dose, route of administration, and thresholds for pharmacokinetic parameters. The degree of acute kidney injury (AKI) is greatest with the intravenous route and higher doses that produce larger maximal concentrations and areas under the concentration curve. Troughs (i.e., minimum concentrations) have less of an impact. Mechanistically, preclinical studies have identified that VIKI is a result of drug accumulation in proximal tubule cells, which triggers cellular oxidative stress and apoptosis. Yet, there are several gaps in the knowledge that may represent viable targets to make vancomycin therapy less toxic. Potential strategies include prolonging infusions and lowering maximal concentrations, administration of antioxidants, administering agents that decrease cellular accumulation, and reformulating vancomycin to alter the renal clearance mechanism. Based on preclinical models and mechanisms of toxicity, we propose potential strategies to lessen VIKI.

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Section: Animal Models and Toxicodynamicsmentioning

confidence: 99%

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

et al. 2020

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“…The costs of a single clinical trial can vary from $5 million for small, non-controlled orphan drug trials to $350 million for large controlled studies. The median estimate is $19 million [31]. Many drugs require several clinical trials prior to gaining authorization for human use.…”

Section: Clinical Trials Randd and Patentsmentioning

confidence: 99%

Recombinant Proteins for Industrial versus Pharmaceutical Purposes: A Review of Process and Pricing

2019

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Recombinant proteins have been produced for over 30 years. Applications range from enzymes used in laundry detergents to antigen-detecting antibodies in cancer therapy. Despite similarities in manufacturing, drastic differences in retail pricing between recombinant proteins used for industrial (non-medical) versus pharmaceutical purposes exist. Industrial proteins often have a retail price in the tens of dollars per kilogram while recombinant proteins for medical use may cost billions of dollars per kilogram. This manuscript will briefly review manufacturing techniques and contrast the differences between industrial versus pharmaceutical production. Maximizing manufacturing technologies to reduce cost-of-goods (CoG) is desirable. However, the major reason for the very high pricing of pharma protein products does not reflect CoG, but the financial obligations of clinical trials, research and development, patent constraints, marketing, and return on investment.

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“…Moreover, trials are expensive due to the involvement of the larger patient populations so as to attain statistical power to provide evidence for smaller therapeutic regimen. 227 The average launch price of anticancer drugs, adjusted for inflation and health benefits, was found to increase by 10% annually from 1995 to 2013. 228 As per the report by the IMS Institute for Healthcare Informatics, cancer drugs' global market has reached $100 billion in annual sales.…”

Section: Cost Of Anticancer Drugs Approved By the Fdamentioning

confidence: 99%

Cancer drug development: The missing links

Kunnumakkara

Bordoloi

Sailo

et al. 2019

Exp Biol Med (Maywood)

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Although better science and technology has been linked with better health care, however, reality is much different. Although America and most of Europe are equipped with most advanced science and technology, paradoxically cancer incidence is highest in the world. This indicates that science and technology alone is not sufficient in treating diseases like cancer. It is also now well recognized that more than 95% of the drugs/compounds that kill either cancer cells in culture or regress the tumors in animals, fail in phase I clinical trials in humans, indicating that most pre-clinical models of cancer are inadequate. In addition, most of the anticancer drugs that are approved by the regulatory agencies such as FDA either has no effect on the overall survival of the cancer patient or may provide an increase in few months in overall survival. This is despite the fact that most targeted therapies that are currently available are highly expensive; thus suggesting the lack of affordability. This review is meant to focus on some of these problems in detail and then provide potential solutions since most cancers are caused by multiple genes, and thus multi-targeted therapies are needed such as natural products which are inexpensive, safe and have been used for thousands of years for both prevention and treatment of cancer. Impact statement The success rate for cancer drugs which enter into phase 1 clinical trials is utterly less. Why the vast majority of drugs fail is not understood but suggests that pre-clinical studies are not adequate for human diseases. In 1975, as per the Tufts Center for the Study of Drug Development, pharmaceutical industries expended 100 million dollars for research and development of the average FDA approved drug. By 2005, this figure had more than quadrupled, to $1.3 billion. In order to recover their high and risky investment cost, pharmaceutical companies charge more for their products. However, there exists no correlation between drug development cost and actual sale of the drug. This high drug development cost could be due to the reason that all patients might not respond to the drug. Hence, a given drug has to be tested in large number of patients to show drug benefits and obtain significant results.

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Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015-2016

Cited by 252 publications

References 8 publications

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

Recombinant Proteins for Industrial versus Pharmaceutical Purposes: A Review of Process and Pricing

Cancer drug development: The missing links

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