Source: http://ipbiz.blogspot.com/2018/07/linear-gadolinum-imaging-agents-and.html
Timestamp: 2019-04-20 22:59:52+00:00

Document:
In this post, we look at how different medical bodies, specifically those in Europe (the European Medicines Agency (EMA) ) and in the United States (the FDA) look at evidence that might be considered "clear and convincing." Specifically, in the context of linear gadolinium imaging agents, they have reached different conclusions. But first, a quick trip to the law of "clear and convincing" evidence.
The Seagate test is also inconsistent with §284 because it requires clear and convincing evidence to prove recklessness. On this point Octane Fitnessis again instructive. There too the Federal Circuit had adopted a clear and convincing standard of [***20] proof, for awards of attorney's fees under §285 of the Patent Act. Because that provision supplied no basis for imposing such a heightened standard of proof, we rejected it. See Octane Fitness, 572 U.S., at ___, 134 S. Ct. 1749, 188 L. Ed. 2d 816. We do so here as well. Like §285, §284 "imposes no specific evidentiary burden, much less such a high one." Ibid. And the fact that Congress expressly erected a higher standard of proof elsewhere in the Patent Act, see 35 U.S.C. §273(b), but not in §284, is telling. Furthermore, nothing in historical practice supports a heightened standard. As we explained in Octane Fitness, "patent-infringement litigation has always been governed by a preponderance of the evidence standard." 572 U.S., at ___, 134 S. Ct. 1749, 188 L. Ed. 2d 816. Enhanced damages are no exception.
A particular quantum or burden of proof at the trial level (standard of proof) is generally a judge-made requirement shaped in accordance with considerations of due process and/or the importance of certain facts. Herman & MacLean v. Huddleston, 459 U.S. 375, 103 S. Ct. 683, 691, 74 L. Ed. 2d 548 (1983). As explicated in Addington v. Texas, 441 U.S. 418, 423-25, 60 L. Ed. 2d 323, 99 S. Ct. 1804 (1979), three levels of proof are generally recognized: preponderance (or weight) of the evidence, clear and convincing proof, and beyond a reasonable doubt.
Although an exact definition is elusive, "clear and convincing evidence" has been described as evidence that "place[s] in the ultimate factfinder an abiding conviction that the truth of its factual contentions are highly probable." Colorado v. New Mexico, 467 U.S. 310, 316, 104 S. Ct. 2433, 81 L. Ed. 2d 247 (1984) (internal quotations omitted).
produce[s] in the mind of the trier of fact a firm belief or conviction as to the truth of the allegations sought to be established, evidence so clear, direct and weighty and convincing as to enable [the factfinder] to come to a clear conviction, without hesitancy, of the truth of the precise facts in issue.
With these definitions in mind, one has some questions about the safety of linear gadolinium contrast agents.
August 29, 2017 — The European Medicines Agency (EMA) issued a final opinion that recommended restricting the use of some linear gadolinium-based contrast agents (GBCAs) and suspending the marketing authorizations of others, while supporting the continued use of macrocyclic GBCAs.
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) earlier this year recommended to suspend some marketing authorisations for Gadolinium Containing Contrast Agents (GCCAs) based on linear chelators due to the potential risk of gadolinium retention in the human body. These recommendations have recently been re-evaluated by EMA's Committee for Medicinal Products for Human Use (CHMP), and confirmed the final opinion of the European Medicines Agency. This editorial provides an overview of the available GCCAs and summarises the recent evidence of gadolinium retention. Moreover, a critical appraisal of the strengths and limitations of the scientific evidence currently available on gadolinium retention is given.
• EMA recommended suspension of some EU marketing authorisations of four linear GCCAs. • Brain MRI findings indicating gadolinium retention have been confirmed by mass spectrometry. • Current scientific evidence for gadolinium retention has several methodological limitations. • No clear clinical evidence exists indicating that gadolinium retention causes neurotoxicity. • Long-term safety of GCCAs, however, remains unclear.
The first committee, the PRAC, found convincing evidence of accumulation of gadolinium in brain tissue many months after the last contrast MRI was performed. (...) It noted deposits had been found in other organs and tissues and non-clinical studies had shown it to be harmful in tissues.
can be seen in the brains of patients who have received multiple doses of gadolinium contrast.
The effect is most noticeable in the globus pallidi, thalami, pons, and dentate nuclei.
and occurs without renal or hepatic dysfunction.

References: §284
 §285
 §285
 §284
 §273
 §284
 v. 
 v. 
 v.