United States: "Regulatory Causation" Roundup

Last Updated: January 13 2017
Article by James Beck

Last week's Westlaw search (that's one way we find the cases we discuss in the Blog) brought a blast from the past – a case almost three years old showed up discussing – and rejecting – expert testimony about so-called "regulatory causation."  Since we'd only touched upon this type of expert opinion once, we thought we'd take a more in-depth look at this concept.

The first thing we discovered is that "regulatory causation" apparently was invented by the ubiquitous Suzanne Parisian, largely for use in the now-mostly-concluded Aredia/Zometa litigation.  That theory was an attempt to dumb down the usual common-law requirements for both causation (ordinarily "more likely than not") and expert certainty (a "reasonable degree of medical" either "certainty" or "probability" depending on the jurisdiction).

As we described in more detail, here, the FDA, being a regulatory agency, is able to intervene prophylactically, before actual harm takes place, in order to prevent such harm.  Thus, the FDA is not bound by common-law causation or expert standards in deciding when a warning should appear on the label for a drug or device.  And the Agency doesn't.  Instead, its regulations governing label changes state the new warnings should be added "as soon as there is reasonable evidence of a causal association [of a risk] with a drug; a causal relationship need not have been definitely established."  21 C.F.R. §201.57(c)(6)(i).  That's for drugs approved after mid-2001.  For some older drugs (without an update since 2001), the standard is similar, although the words vary:  "as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved." Id. §201.80(e).  See In re Incretin-Based Therapies Products Liability Litigation, 142 F. Supp.3d 1108, 1120 (S.D. Cal. 2015) (describing how these regulations work).  For medical devices, the equivalent standard is harder to locate, since the FDA's "labeling" regulations for devices does not address when to change a label.  For PMA devices a standard of sorts – "reasonable evidence of a causal association" – in the CBE provisions applicable to such devices.  21 C.F.R. §814.39(d)(2)(i).

For §510k devices, label changes of this sort appear to trigger resubmission requirements, which is getting rather far afield from the topic of this post. However, it is in connection with such a device where Parisian's "regulatory causation" terminology first appears in a decision on either Lexis or Westlaw.  While it's not much of a discussion, it is favorable – excluding the testimony:

Regarding Opinion 3 . . . that [defendant] did not conduct an adequate review of scientific and medical literature to identify potential risks . . . Plaintiff presents Dr. Parisian as a regulatory expert, not a medical expert[,] . . . stating that Dr. Parisian's opinions are offered to a degree of "regulatory certainty," not "medical certainty" and speaking of "regulatory causation" rather than "medical causation". . . . Plaintiff does not argue that Dr. Parisian has the required expertise to offer such an opinion.

Miller v. Stryker Instruments, 2012 WL 1718825, at *11 (D. Ariz. March 29, 2012). Thus, Dr. Parisian's "regulatory causation" testimony regarding a §510k medical device, whatever it might have been, was excluded because she had no expertise qualifying her to offer causation opinions.

That doesn't mean, however, that Parisian hadn't tried the same thing before. In In re Trasylol Products Liability Litigation, 709 F. Supp. 2d 1323 (S.D. Fla. 2010), the same Parisian opinions, couched solely as "causal association," were also excluded.  The opinion quoted cross-examination that described such testimony as "a back door causation opinion in the guise of talking about information available and regulatory affairs."  Id. at 1340.

Then Parisian became active as a plaintiff-side expert in Aredia/Zometa and started spewing "regulatory causation" opinions all over the place.  Courts were rightly skeptical.  The first court to encounter such an opinion in this context was "not convinced by Plaintiff's arguments distinguishing medical causation from causal association." Georges v. Novartis Pharmaceuticals Corp., 2012 WL 9064768, at *10 (C.D. Cal. Nov. 2, 2012).  Plaintiff sought to distinguish "between medical causation, which Parisian described as "the result of causally randomized clinical trials," and "regulatory causation," which was "not the standard of medical causation" at all, but rather (as we mentioned above and discussed in our earlier post), but only the amount of data that "would trigger a manufacturer to have to change their warnings due to causal association."  Id. (internal quotation marks omitted).

Thus, Parisian hoped to focus the jury on the FDA "causal association" standard for label changes rather than on controlling common-law causation requirements. This, the court found, could only cause "confusion."  "Dr. Parisian's attempt to draw this distinction is confusing at best and would almost certainly confuse or mislead the jury."  Id. (relying on Brown v. Novartis Pharmaceuticals Corp., 2012 WL 9082913 (Mag. E.D.N.C. Jan. 9, 2012), adopted in pertinent part, 2012 WL 9082901 (E.D.N.C. Feb. 3, 2012)). Brown, while not using the term "regulatory causation," was discussing the same thing, and reached the same result.  Id. at *7 ("plaintiffs' attempt to distinguish causal association from medical causation [is] confusing and generally ineffective").  These cases were spot on, since the whole point of such testimony is to sow confusion – to offer a false "regulatory" standard to a common-law jury.

In the case we discussed previously, Guenther v. Novartis Pharmaceuticals Corp., 2013 WL 1278089 (M.D. Fla. March 28, 2013), the plaintiffs had stipulated that Parisian wouldn't testify "about medical causation."  Id. at 2.  Instead, plaintiffs trotted out Parisian's "regulatory causation" testimony based on the FDA's "causal relationship need not have been definitely established" regulatory language.  The Guenther court was having none of it, recognizing this dodge for what it was:

The Defendant argues that allowing Parisian to testify regarding [defendant's] compliance with that regulation is effectively the same as allowing her to testify regarding medical causation, allowing her to make an end run. . . . Plaintiffs' counsel responds that "causal association" is an FDA term, rather than a medical term, and that Parisian as an FDA compliance expert should be permitted to testify in regard to that term.  Aside from its origin, however, Plaintiffs' counsel offers nothing to meaningfully distinguish "causal association" from medical causation. . . .  Parisian will not be permitted to offer opinions regarding any alleged "causal association" between ONJ and Zometa.

Id. at at *7. A few days later, another judge in the same federal district adopted Guenther's conclusion verbatim in an other A/Z case.  Dopson-Troutt v. Novartis Pharmaceuticals Corp., 2013 WL 1344755, at *3 (M.D. Fla. April 2, 2013).  See also Kirchman v. Novartis Pharmaceuticals Corp., 2014 WL 12617778, at *5 (M.D. Fla. May 22, 2014) ("Plaintiff's regulatory causation argument in this case does not differ from the one made by the Dopson-Troutt plaintiff.  The Court adopts its Dopson-Troutt reasoning and precludes Dr. Parisian's opinions regarding regulatory causation.").

These cases set the trend.  Parisian's testimony – sometimes labeled "regulatory causation" and elsewhere called "causal association" after the language she lifted from §201.57, was excluded as disguised medical causation testimony, about which Parisian was utterly unqualified to testify, and which would also confuse the jury:

[R]egulatory causation or "causal association" is also outside Dr. Parisian's expertise and should be excluded. . . . Plaintiffs' counsel fails to meaningfully distinguish the causal association outlined in §201.57(c)(6)(i) from medical causation, and as such, testimony on this issue must be excluded.  Dr. Parisian's discussion of regulatory causation would not be beneficial to the jury's decision-making process, and is thus not permissible.

Kruszka v. Novartis Pharmaceuticals Corp., 28 F. Supp.3d 920, 934-35 (D. Minn. 2014) (citations omitted). See Gilliland v. Novartis Pharmaceuticals Corp., 2014 WL 11581411, at *1 (S.D. Iowa July 30, 2014) ("The Court finds Kruszka persuasive, and, accordingly, adopts both its reasoning and conclusions").

Parisian will not be permitted to offer causation testimony of any kind, including "regulatory causation" or "causal association" opinions related to compliance with 21 C.F.R. §201.57.  Plaintiffs have failed to sufficiently differentiate such testimony from general medical causation testimony, which [she] is not qualified to give.

Rowland v. Novartis Pharmaceuticals Corp., 9 F. Supp.3d 553, 562 (W.D. Pa. 2014).

The Court agrees with the Georges Court that "Dr. Parisian's attempt to draw [a] distinction between medical causation and causal association is confusing at best and would almost certainly confuse or mislead the jury."  Dr. Parisian is not qualified to give medical causation testimony . . . , and allowing Dr. Parisian to testify on this issue would impermissibly allow the jury to reply on Dr. Parisian's opinion regarding [causation].

Stanley v. Novartis Pharmaceuticals Corp., 2014 WL 12573393, at *4 (C.D. Cal. May 6, 2014).

[Parisian's] opinion relates to "causal association" under 21 C.F.R. §201.57. This regulation requires that a product's "labeling must be revised to include a warning about a clinically significant hazard as soon as there is reasonable evidence of a causal association with a drug."  The Court finds that Plaintiff has failed to establish how this opinion significantly differs from medical causation.  Additionally, Plaintiff has not demonstrated that Dr. Parisian is qualified to identify when a "causal association" with a drug emerges which necessitates a labeling change.

Taylor v. Novartis Pharmaceuticals Corp., 2013 WL 5118945, at *9 (S.D. Fla. Apr. 22, 2013) (citation omitted).

Defendant maintains that Dr. Parisian will testify about regulatory causation.  Specifically, Dr. Parisian will testify about the types of evidence that the FDA would consider in determining the "association of a serious hazard with a drug."  However, regulatory causation is not recognized as a legitimate form of causation.  In fact, Dr. Parisian does not even address regulatory causation in her report.  Accordingly, Dr. Parisian is precluded from testifying about regulatory causation.

Monroe v. Novartis Pharmaceuticals Corp., 2014 WL 12586426, at *3 (S.D. Ohio Sept. 15, 2014) (footnotes omitted).

[Courts] have not allowed Dr. Parisian to testify at all with respect to causation, finding her unqualified. . . .  Because Dr. Parisian was not qualified to diagnose [the condition], neither was she qualified to offer an opinion concerning the propriety of [defendant's] actions.  The Court finds this reasoning persuasive.  Accordingly, Dr. Parisian will not be permitted to testify about "regulatory causation" or a "causal association" between bisphosphonate drugs and ONJ.

Mathews v. Novartis Pharmaceuticals Corp., 2013 WL 5780415, at *24 (S.D. Ohio Oct. 25, 2013) (citations omitted).

Defendant raises legitimate concerns about the risk of unfairly prejudicial or confusing testimony.  It is not the role of Dr. Parisian to offer legal conclusions on any topic. . . .  Dr. Parisian is not permitted to testify to things outside of her expertise.  This includes testimony that may be couched as regulatory causation but in actuality speaks to medical causation.

Stambolian v. Novartis Pharmaceuticals Corp., 2013 WL 6345566, at *9 (C.D. Cal. Dec. 6, 2013).

Thus, from the opinions available on Westlaw (and Lexis), it appears that, in the Aredia/Zometa litigation, Parisian was never allowed to attempt to bamboozle juries with a standard for "regulatory" causation that was lower, and more plaintiff-friendly, than the common-law causation burden of proof in tort cases.  One problem may have been that she submitted the same "boilerplate" report in "all" cases.  Monroe, 2014 WL 12586426, at *3 n.6.

However, Parisian's singular lack of success doesn't seem to have deterred her (or counsel retaining her), since the she popped up to offer the same opinions – with the same exclusionary result − in more recent Mirena IUD litigation.  In the same epic opinion (making our 2016 top ten) that threw out all of the plaintiffs' causation experts in the Mirena MDL, the court also rejected Parisian's "regulatory causation" retread.

Parisian's testimony related to "causal association" − as this term is used pursuant to 21 C.F.R. §201.57(c)(6)(i) − is also inadmissible because Plaintiffs have not "sufficiently differentiate[d]" testimony related to causal association from general medical causation. . . .  Defendants' motion with respect to testimony relating to medical causation or regulatory causation is granted.

In re Mirena IUD Products Liability Litigation, 169 F. Supp.3d 396, 476 (S.D.N.Y. 2016) (citing Rowland and Dopson-Troutt) (footnote omitted).  The same opinion yielded the same result.  "Parisian will not be permitted to testify that the [drug's] label should have been changed to warn of [the risk], because she is not qualified to say either that that risk was clinically significant or that there was reasonable evidence of causal association."  Id. at 476 n.76.

So, if you encounter Parisian, or any other P-side expert, seeking to offer opinions about "causation," in a warning case involving label-change allegations, and the opinions are couched in FDA regulatory language rather than the more stringent common-law causation standard, don't hesitate to come down on those opinions like a ton of bricks.  Such opinions are a transparent attempt to confuse the jury into ignoring applicable law – so transparent that no opinion we've been able to find has allowed such opinions to be heard by a jury.

This article is presented for informational purposes only and is not intended to constitute legal advice.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

James Beck
In association with
Related Topics
Related Articles
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.


The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.


Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions