General Interest

Some Thoughts on the New Common Rule for Human Subjects Research

On January 18, 2017, in one of its last official acts, the outgoing Obama administration issued a final revised version of the Common Rule—the regulation that governs the treatment of human subjects in all federally funded research. This was the culmination of a process that began in 2011 when the Department of Health and Human Services (HHS) issued an Advance Notice of Proposed Rulemaking, or ANPRM, that envisioned major changes to the original 1991 Common Rule. Then, on September 8, 2015, HHS and 15 other federal departments and agencies released a Notice of Proposed Rule Making (NPRM) that proposed specific changes to the Common Rule and opened a 90-day public comment period.

The NPRM’s proposed changes would have greatly altered the rules for human subjects research, especially regarding biospecimens. Among the most controversial of its proposals was the expansion of the definition of regulated “human subjects research” to include research using anonymous or deidentified human biospecimens. This is a critical point because research that does not involve human subjects at all is not subject to the Common Rule’s requirements. The comments from industry, research universities, and scientific and professional organizations were highly critical of some of the proposed changes. There was an evident division between (critical) hard science and (supportive) social science (anthropologists, for example) commenters; bioethicists were generally critical, but there were opinions on both sides. In a previous GLR post, I reported on a withering critique of the biospecimen proposal from the National Academies of Sciences, Engineering, and Medicine, which argued that “continuing expansion of federal regulations on research is diminishing the effectiveness of the U.S. research enterprise.”

The January 18 final version (the “Final Rule”) adopts some of the changes proposed in the NPRM and drops others, including the controversial expansion of the definition of “human subjects” to include non-identified biospecimens. The official text of the Final Rule appears here.

As you can see, this is a daunting 500-plus-page document. However, the complete text of the Final Rule appears at pp. 459-508, with an executive summary of the new provisions at pp. 360-362. The rest of the document consists of numerous tables (cost-benefit analyses and the like) required by law and a summary of and response to every public comment made in 2015.

There have already been numerous published summaries of the differences among the original Common Rule, the NPRM version, and the Final Rule. The most comprehensive of these may be from the Council on Governmental Relations.  A second article, from the New England Journal of Medicine, summarizes and analyzes how the Final Rule differs from the NPRM from the medical research perspective. A third, from a higher education journal, focuses more on the social science perspective and links to several other analyses. A fourth piece, from Science, cites the bioethical critique of the new Final Rule.

Without trying to reinvent the wheel, here are some of the key provisions of the Final Rule that these sources point out:

Is the Final Rule Really “Final”?

The answer here is a resounding “probably.” A 1996 law called the Congressional Review Act allows the House and Senate to eliminate new agency regulations by passing a joint resolution of disapproval within 60 days of being notified of a new rule. As with an ordinary bill, the resolution would be subject to presidential signature or veto. (President Obama vetoed five such resolutions—the only times the CRA has been used.) The 60-day period apparently expired on March 20 without any congressional action, though there is debate over what it means for Congress to be “notified.”

The new administration could announce yet another rulemaking—this one intended to modify or eliminate the Final Rule. The administration could also attempt to change the practical application of the Final Rule through informal “guidance,” which was the subject of an earlier GLR post.

There is no reason to believe that any of these things will happen. The criticism of the NPRM did not follow partisan or ideological lines—just about everyone involved in research, from university medical centers to Big Pharma, opposed many of its provisions. The fixes reflected in the Final Rule seem pragmatic and not calculated to trigger political responses from either the legislative or executive branch. With the exception of some in the bioethics community, virtually all constituencies are supportive. And most importantly, no one in Congress or the administration has—as far as I can tell—expressed any interest or concern. So the prudent assumption is that the Final Rule really is final.

Why Are Some Bioethicists Unhappy?

Several prominent bioethicists have criticized the failure to require informed consent for research on anonymous or deidentified human biospecimens. Hank Greely of Stanford has called it “a predictable result of the disparity in lobbying power” between the research and subject communities. Another critic is Rebecca Skloot, the author of the best-selling The Immortal Life of Henrietta Lacks, about a poor African-American woman whose cells—without her knowledge or consent—gave rise to the HeLa cell line and, directly and indirectly, generated large amounts of money in which she and her descendants have never shared. A Lacks descendant has recently sued Johns Hopkins University in a belated effort to seek compensation. The suit faces many significant legal challenges—the biggest of which may be the statute of limitations.

What specific harms to subjects are the critics worried about? The possible harms seem to fall into three broad categories: privacy-related, emotional, and financial. On the privacy issue, Skloot has noted that Mrs. Lacks ultimately lost her anonymity, and that she and her family endured the public disclosure of personal medical information. That’s a rare event, as Skloot has acknowledged. In fact, it’s hard for me to see realistic invasion-of-privacy concerns in the current research environment, regardless of how the Common Rule treats biospecimens. When I ask the question—Is there a measurable probability that someone will have the means and motive to re-identify my DNA sample and then use that information to harm me?—my answer is no.

Skloot has also drawn on the Lacks family’s experience to catalogue the possible emotional harms, including “the shock of learning they were part of research” and being drawn into “debates over who controlled samples” and how those samples could be used. I wouldn’t judge someone else’s reaction to these consequences, but I would discount it by the current probability of similar things happening—and Skloot deserves much of the credit for bringing attention to the issue and thereby reducing that probability.

I think the most serious consequence is what Skloot has called “questions over profits.” A lot of people and institutions made money from Henrietta Lacks’s cells. She didn’t get any of it, and she was never told that the research was going on. The same thing has happened in a couple of other notorious cases, most infamously the 1990 California case of Moore v. Board of Regents. This bothers me. If I’m considering giving you a biospecimen and you think you might use it for money-making purposes, you should tell me. Some people might refuse your request outright; I would personally want the opportunity to negotiate for a piece of the action.

Curiously—to me—the research and bioethics communities have almost uniformly rejected the ideas that an informed consent document is a contract and, especially, that money can be used as an inducement to contribute a research biospecimen (though they do approve of token payments as compensation for the subject’s inconvenience). A few years ago, several colleagues and I published two articles advocating a contractual model for biospecimen contributions to biobanks. The key idea was a sliding scale of compensation: the more control over the sample that the subject ceded to the researcher, the more the subject would get paid.

The reaction, in print and at conferences where we presented the papers, was very negative. Allowing subjects to treat their DNA as a commodity seemed to be viewed as per se unethical. I remember one anonymous journal reviewer—who advocated rejecting the article—writing that we had totally ignored the lessons of the Henrietta Lacks case. We thought that we had come up with a way to prevent the same thing from happening in the future. The lesson I took away from the whole experience was that, to our critics, subject autonomy was little more than a rhetorical construct.

How Much Does the Final Shape of the Common Rule Really Matter?

At least with respect to research using biospecimens, the answer may be: not all that much. The reason is that many, many people are regularly consenting to the use of their biospecimens without ever becoming aware of it.

I owe this realization to Jean Cadigan, a medical anthropologist at UNC Medical School, who co-teaches my Biotechnology and Life Sciences course at UNC Law School. In a recent class, Jean led us through a fascinating exercise about consent to research in teaching and research hospitals (most use very similar forms, so these comments could apply to almost any university medical center). First, she showed us an elaborate, carefully crafted informed consent video used by a university-affiliated biobank. The biobank offers all the protections that the Common Rule requires and more. Then we looked at a specific consent for treatment form. By way of preamble, I should note that I and family members whom I’ve accompanied to various hospitals have had to sign this kind of document on several occasions in exigent circumstances. I’ve never read one—and I bet you haven’t either. I’m a lawyer and I teach this stuff, but the consent form is the last thing on my mind in the emergency room. I’ll scribble my name on anything they put in front of me just to get the treatment started.

But what would I find if I did read it? In the example we looked at, at the end of a long paragraph entitled “Consent for Use and Release of Information,” I’d see that the patient gives the hospital permission “to release any information about me, my health, the health services provided to me . . . (4) as otherwise described in the Notice of Privacy Practices and as permitted by law.” Then, if I dug up that Notice (as Jean did for our students), I’d find that the hospital (taking advantage of a HIPAA exception) asserts the right, “without [the patient’s] authorization or an opportunity to agree or object,” to use or disclose personal health information or “surplus specimens” (anything they take out of your body that they don’t put back in) as long as “the use and/or disclosure relates to research.”

The bottom line appears to be that, however the Common Rule treats biospecimens, the research world will still be awash in unwittingly donated—and not anonymized—tissue samples. This makes the anguish over the Final Rule, and the ethical aversion to our contractual model, seem like rearranging the deck chairs on the Titanic.

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Filed under Genomics & Medicine, Informed Consent, Patents & IP

Williams v. Athena Motion to Dismiss Hearing—SC Supreme Court May Be Asked to Decide Whether a Diagnostic Laboratory Qualifies as a Healthcare Provider

Foreword by John Conley 

Back on May 31, 2016, Contributing Editor Jennifer Wagner wrote a lengthy report on the newly filed case of Williams v. Quest Diagnostics, et al. As Jen recounted, plaintiff Amy Williams sued Athena Diagnostics and its corporate parent, Quest Diagnostics, alleging that Athena negligently misclassified a genetic variant it identified in testing the DNA of her late son. Ms. Williams claims that the misclassification caused the boy’s doctors to prescribe a potentially dangerous course of treatment that ultimately led to his death. The case was originally filed in a South Carolina state court and was then removed to federal court by the defendants, which they were able to do because the parties are citizens of different states.

As Jen also reported, the defendants responded by filing a motion to dismiss the complaint. Their principal argument was that the case is actually a medical malpractice case, rather than an ordinary negligence, and as such is barred by the applicable statute of limitations. Federal Judge Margaret B. Seymour conducted a lengthy hearing on that motion on January 4, 2017. There has been no ruling as yet, nor any timetable for one.

Laurel Coons, a Duke University Ph.D. student, is working on the case with GLR Contributor Robert Cook-Deegan, M.D., formerly of Duke and now of Arizona State University, who has filed an expert affidavit on behalf of Ms. Williams. Laurel attended the hearing, and she and I have reviewed the transcript. Laurel’s report and analysis of what happened follows. I add a few legal comments at the end of Laurel’s post.

Williams v. Athena Motion to Dismiss Hearing—SC Supreme Court May Be Asked to Decide Whether a Diagnostic Laboratory Qualifies as a Healthcare Provider

By Laurel Coons

Laurel A. Coons is a Ph.D. candidate at Duke University. She received her B.S. in biology and M.S. in biotechnology from the University of South Carolina.

The South Carolina Supreme Court may be asked to certify whether a diagnostic lab should be classified as a health care provider under state law. South Carolina federal Judge Margaret Seymour appeared to be contemplating this during a January 4 hearing on the defendant’s motion to dismiss in the Williams v. Quest Diagnostics, Inc. lawsuit. The answer will determine whether this lawsuit will move toward a jury trial.

The Complaint – March 2016
Christian Millare was born in August 2005 and beginning at the age of 4 months started having seizures. His doctors treated his seizures with sodium channel inhibitor medications: oxcarbazepine (Trileptal®), carbamazepine (Tegretol®), and lamotrigine (Lamictal®). These are standard treatments for epileptic seizures not caused by Dravet syndrome (SMEI). In January 2007, Christian’s DNA was sent to Athena Diagnostics (a subsidiary of Quest starting in 2011) for a DNA analysis of the SCN1A gene—that is, the detection and diagnosis of any DNA variants within the SCN1A gene. DNA mutations in SCN1A are associated with a spectrum of epilepsy phenotypes, the most severe being Dravet syndrome. For patients with SCN1A mutations, sodium channel inhibitor medications are to be avoided because they exacerbate the seizures. The DNA sequencing of Christian’s DNA took place in May 2007. The results were sent to the ordering physician, John Shoffner, on June 30, 2007. This report indicated that Christian possessed a DNA variant in the SCN1A gene that was classified as a “variant of unknown significance” or VUS (i.e., not specifically known to be either pathogenic or benign). Relying on the information in this report (which did not identify any DNA variants as being pathogenic or warn of any treatments to avoid), Christian’s doctors continued to treat him with increasing doses of multiple sodium channel inhibitor medications. Athena did not issue a copy of the June 2007 report directly to the patient or the patient’s family. Christian’s condition worsened, even as doses of the sodium channel inhibitor medications were increased in attempts to manage his seizures. Christian suffered a severe and ultimately fatal seizure resulting in his death on January 5, 2008.

His mother, Amy Williams, sued Athena and Quest, its parent company, in a South Carolina state court in March 2016. The defendants were able to “remove” the case to the South Carolina federal court because the plaintiff and defendants are citizens of different states. Nonetheless, South Carolina state law will continue to apply.

The complaint alleges that Athena was negligent and breached the applicable standard of care by (1) failing to provide a genetic confirmation that Christian had Dravet syndrome and (2) failing to adhere to its own DNA variant classification criteria. The alleged negligent misclassification of Christian’s DNA variant originates from the fact that in 2007, Christian’s DNA variant had been reported, studied, and known in a patient with Dravet syndrome. Specifically, a genotype-phenotype association between his variant and Dravet syndrome had been established in two clinical publications, Berkovic et al., 2006, and Harkin et al., 2007. Per Athena’s DNA variant classification criteria as defined in the June 2007 report, the requirement for deeming a variant to be a “known disease-associated mutation” was whether it was reported in the literature to be associated with the disease. Thus, the plaintiff alleges, the existence of Berkovic et al., 2006 and Harkin et al., 2007 made Athena’s classification of Christian’s variant as VUS (i.e., “has not been correlated with clinical presentation and/or pathology in the current literature”) demonstrably false. According to the June 2007 report, “the results of this analysis cannot be definitively interpreted due to the absence of published studies correlating these variant(s) with clinical presentation and/or pathology.”

Christian’s June 2007 report was signed off by Sat Dev Batish, chief director of genetics at Athena, and also an author of the Harkin et al., 2007 publication. According to the complaint, Christian’s DNA variant was cited as an SCN1A DNA mutation that “disrupts the functioning of an assembled ion channel so as to produce an epilepsy phenotype” in a patent for SCN1A testing. This patent originated from the laboratory that produced the Berkovic et al., 2006 and Harkin et al., 2007 publications—the same laboratory that also licensed use of the patent for SCN1A testing to Athena in 2004. Thus, the information used to gain patent rights of SCN1A testing included a citation of Christian’s variant causing an epilepsy phenotype. Finally, the June 2007 report lists a manuscript that was published in 2005 as “pending,” suggesting that Athena’s integration of the biomedical literature into their DNA variant database was at least two years behind.

Hearing on Defendant’s Motion to Dismiss – January 4, 2017
During the oral argument on the defendant’s motion to dismiss held on January 4, 2017, Quest/Athena argued that Williams’s allegations of negligence are in fact allegations of medical malpractice, and, as a result, are time-barred. In South Carolina, plaintiffs have three years to bring a medical malpractice suit against a licensed healthcare provider (who has a direct fiduciary duty to a patient) from the time they discover they were harmed, but they lose the right to sue entirely after six years. This absolute six-year bar is called a statute of repose. Williams’s lawyer, however, argued that her claims allege not medical malpractice but ordinary, common law negligence, which is not subject to the statute of repose. The specific negligence alleged is Athena’s failure to reference (in the June 2007 report) the published studies associating Christian’s specific mutation and SMEI in another patient (Berkovic et al., 2006 and Harkin et al., 2007). Williams further alleges that Athena’s failure to abide by its DNA variant classification criteria, as defined in the June 2007 report, constituted a breach of general laboratory duty, which subsequently led to Christian’s physician failing to discontinue potentially harmful medications. As noted above, Quest/Athena’s own standard for deeming a DNA variant to be pathogenic, or disease-causing, as defined in the June 2007 report, was whether that DNA variant was reported in the literature to be associated with the disease in question.

At the hearing, Williams’s lawyer argued that these are acts of ordinary negligence, with a three-year statute of limitations that didn’t start to run until she discovered the negligence. Williams claims she was unaware of the June 2007 report until September 2014, at which time the June 2007 report was requested and received from Athena. During this 2014 interaction with Quest/Athena, Williams learned that the variant had now been deemed disease-causing and the report would be revised. Quest/Athena subsequently issued a revised report with the new classification of “known disease-associated mutation” on January 30, 2015. Williams contends that she had no opportunity to discover the defendants’ error until she had both the June 2007 and January 2015 reports in hand. Quest/Athena argued that it doesn’t matter whether or not the plaintiff herself knew or did not know about the 2007 report, because “the actual knowledge is imputed to the principal by virtue of [her] agent’s notice”—the agent in this case being the physician, John Shoffner, who ordered the test and received the June 2007 report. Williams also contends that Athena’s failure to notify anyone of the reclassification of Christian’s DNA variant prior to January 30, 2015 was a daily, recurring failure to comply with CLIA regulations, and thus represents a continuous and ongoing injury, each instance allowing for a new claim and thus starting a new clock.

How the judge decides this matter depends on whether Quest/Athena, a CLIA-certified clinical laboratory and “one of the leading genetics testing laboratories in the world,” is a licensed healthcare provider under South Carolina law. Specifically, can a lab that doesn’t deal directly with a patient have a professional, fiduciary relationship with the patient triggering a malpractice standard? Quest/Athena further explained that they “weren’t permitted to do so [communicate individually with patients],” and that consequently “it would have been completely inappropriate for Athena to communicate directly with any patient.”

At the hearing, Judge Seymour asked both the plaintiff and the defendants whether the question of malpractice versus ordinary negligence should be certified to the South Carolina Supreme Court. Certification is a procedure whereby a federal court may pose an undecided question of state law to a state supreme court. Since South Carolina state law will govern this case, the federal judge would then have to follow the South Carolina Supreme Court’s answer.

Other Issues
a) Initial Report – June 2007: Variant of Unknown Significance
According to the complaint, Williams believes that because a genotype-phenotype association between Christian’s DNA variant and Dravet syndrome had been established in two clinical publications (Berkovic et al., 2006 and Harkin et al., 2007), the June 2007 report should have classified Christian’s mutation as a “known disease-associated mutation” rather than a VUS. The existence of these two clinical publications would apparently satisfy the requirements of a “known disease-associated mutation” per Athena’s own DNA variant classification criteria as defined in the June 2007 report. (The requirement for deeming a variant to be disease-causing was whether it was reported in the literature to be associated with the disease.) Williams further alleges that classifying Christian’s DNA variant as a VUS in 2007 was incorrect per these same DNA variant classification criteria: “Variants of unknown significance are DNA sequence variants that are detected reproducibly, but have not been correlated with clinical presentation and/or pathology in the current literature.”

At the hearing Athena’s lawyer argued that “the patient that is identified (in Berkovic et al., 2006 and Harkin et al., 2007) as having the same genetic mutation” had, in both papers, a de novo” mutation. That is, the mutation was not inherited but instead arose during cell division of egg or sperm or early embryonic development. The defense further contended that parental testing is required to determine whether a mutation is de novo, and thus “within the classification that was in those two published reports because the patients in those reports had a de novo mutation.” According to this argument, Athena has no way to know “whether or not this serious disease is present in this mutation unless we test the parents.” The lawyer’s point was that Athena could not have known whether Christian’s mutation was de novo—and thus the same as the mutation in the published papers—because his parent did not undergo genetic testing. As noted above, however, Williams contends that, because she was unaware of the June 2007 report, she was unaware that testing of the biological parents (de novo determination) was recommended.

Athena’s lawyer pointed to patient #15 on Supplement Table 2 of Harkin et al., 2007 (a female who possessed the same mutation as Christian whose mutation was confirmed to be de novo) to illustrate that a conclusive diagnosis could be reached only by additional parental testing and de novo determination. It is intriguing that the next patient listed (#16), along with thirteen other patients on this table, had the same classification as patient number #15 but de novo status was not determined. According to Harkin et al., 2007, “in cases with missense changes, where DNA from parents is unavailable…the case for pathogenicity rests on circumstantial evidence provided by evolutionary conservation of protein structure.” Further, if parental testing was never done on Christian because his parents were unaware of this recommendation, and de novo determination was required for the DNA variant to be classified as a “known disease-associated mutation,” it is hard to understand how and why his DNA variant was reclassified to a “known disease-association mutation” sometime after the June 2007 report and before September 29, 2014.

b) Revised Report – January 2015: Known Disease-Associated Mutation
During the hearing, Judge Seymour seemed particularly interested in understanding the origin and details of the revised January 2015 report. Although the January 2015 report reclassified Christian’s variant from VUS to disease-causing, it did not list any new references or data supporting that reclassification, it did not list the Berkovic et al., 2006 or Harkin et al., 2007 papers, nor did it identify the date when the reclassification occurred or who corrected the misclassification.

Judge Seymour wanted to know why the 2007 report was revised. Athena’s lawyer said that “there was an update to the classification of the mutation in Athena’s database,” and that “as soon as the information became known that it was applicable to this situation, the update was provided to the requesting individual.” Athena’s lawyer further explained,

“the plaintiff’s genetic counselor called Athena in 2014 and asked Athena to re-look up the variant. Athena did so and saw that the variant, the mutation, had been reclassified since then in its database, and based on additional information that was available since June of 2007—remember, this is an incredibly fast-paced field—more than seven years later when the variant was looked up in the database to see how it’s classified. Classifications of variants do change based on new information, and that is what happened here. It’s not a reclassification based on an error. It was just based on new information” [Of note, according to the complaint, Athena was contacted in 2014 to in order to obtain the 2007 report for the first time, not to “re-look up” a variant.]

Athena’s lawyer did not explain what “new information” was obtained between June 2007 and September 2014 that resulted in the reclassification of Christian’s DNA variant (1237T>A, Y413N) from a “variant of unknown significance” to a “known disease-associated mutation.” According to the January 2015 report, “analysis of this individual’s SCN1A gene identified a DNA sequence variant that has been reported in the literature to be associated with SMEI or SMEB, the severe phenotypes associated with SCN1A mutations.”

Event Timeline
Event timeline was prepared and presented by Laurel Coons and Robert Cook-Deegan for the Committee on Science, Technology and Law of the National Academies of Science, Engineering and Medicine for their session on Diagnostics Labs and Legal Liability on October 17, 2016.

Afterword by John Conley

I appreciate Laurel’s careful and accurate reporting, and I think her analytical points are all well taken. I’d add just a few points from a legal perspective:

1. Judge Seymour did an excellent job in conducting the hearing. She was very well prepared and had an impressive understanding of the medical and scientific issues. She pressed both sides on their respective vulnerabilities, and both lawyers were sometimes wobbly in responding. That’s not a criticism of them, but a reflection of the fact that—as Laurel points out—both sides face some hard issues. In any event, if the case goes forward from here, all indications are that Judge Seymour is the right judge to manage it, with all its complexities.

2. Don’t try to predict the outcome from the judge’s questions. Judge Seymour was just doing her job, very effectively: forcing both sides to deal squarely with their hardest issues. To me, she seemed absolutely evenhanded in her questioning. I see no basis for predicting how she’s leaning.

3. What happens from here? This is complicated. An initial point to keep in mind is that (under a 1937 U.S. Supreme Court case) the federal judge must apply South Carolina state law—not federal law—to all of the key issues in this case. So, a big part of Judge Seymour’s job here is to determine what South Carolina law says about those issues.
Let’s break down the possibilities:

(a)  Judge Seymour decides on her own that the case is or is not a malpractice case and then applies the applicable statute of limitations. If she decides that it is a malpractice case, then the likely outcome is that it will have to be dismissed under the six-year statute of repose that Laurel describes. The plaintiff could then appeal to the U.S. Court of Appeals for the Fourth Circuit, which covers Maryland, Virginia, West Virginia, and North and South Carolina. If Judge Seymour decides it isn’t a malpractice case, she would apply the ordinary negligence statute, which doesn’t have a statute of repose, and the plaintiff might well (although not necessarily) avoid dismissal. If that happens, the parties will begin discovery and the case will begin moving slowly toward trial.

(b)  In this scenario, Judge Seymour doesn’t decide the malpractice versus ordinary negligence issue herself, but certifies that question (as Laurel explains) to the South Carolina Supreme Court for an answer. If she does that, and the South Carolina court accepts the question, that would add a minimum of several months to the process. Depending on the South Carolina court’s answer (which Judge Seymour would be bound to follow), the case would unfold as described in paragraph (a).

4. Regardless of which way the decision goes, what will be the legal impact? Surprisingly, perhaps, the strictly legal significance of the case will be limited. A number of scientific and medical people have suggested to me that, because the case is in federal court, it will have national impact. That’s not true, at least from a legal perspective. Again, let’s review the possibilities.

If the South Carolina Supreme Court decides the malpractice versus negligence question (or any other question in the case that may be certified to it), its answer will be binding on all South Carolina state courts, and, indirectly, on other courts, state or federal, that have to decide that same question under South Carolina law (not many, I’d think).

Any decision made by Judge Seymour on this or any other issue in the case won’t be binding on any other court. Any rulings made on appeal by the Fourth Circuit will be binding on all federal courts within the circuit’s five states. But here again, those rulings would apply only in federal cases that happened to be deciding the very same questions under South Carolina law. A final point is that this case is very unlikely to be taken by the U.S. Supreme Court because it does not seem to present a significant question of federal or constitutional law.

This all adds up to minimal significance. Note, however, that I keep stressing that I’m referring to strictly legal significance. It could be highly significant in other respects. First, if Judge Seymour’s rulings on all the issues the case presents seem well reasoned and persuasive, then other courts facing similar issues might choose to follow her. This happens often, with the first case on a novel problem becoming the model for later decisions elsewhere. So, if Judge Seymour ultimately rules on, for example, the respective standards of care for labs, medical geneticists, and primary care physicians in this factual context, judges in later cases will look carefully at her reasoning and may follow it, even though they won’t have to.

In addition, as legislators and regulators think about how to regulate genomic testing, they will be looking for any precedent that might provide guidance. If this case gets past the statute of limitations issue and Judge Seymour issues rulings on substantive issues, lawmakers (or their staffs) will look closely at what she says.

5. This leads to my final point: a message for the medical and scientific communities. Everyone involved in developing a legal framework for genomic testing—judges, legislators at the state and federal levels, and state and federal regulators—is and will be looking for guidance. Help them out! It would be very useful for interested expert bodies—the Association for Molecular Pathology, for instance—to promulgate guidelines for resolving such critical questions as the respective responsibilities of primary care physicians, specialists, and testing labs in situations such as that presented by the Williams case. If you do, I can almost guarantee that the relevant legal constituencies will take your recommendation very seriously. But if judges, legislators, and regulators are left to make it all up on their own, you probably won’t like the outcome. And act now, not later. Plaintiffs’ lawyers are given to herd behavior, so the Williams case may be only the first.

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Filed under General Interest, Genetic Testing/Screening, Genomics & Medicine, Legal & Regulatory, Pending Litigation

Update on Chadam v. Palo Alto Unified School District

About a year ago we reported on a case involving allegations of genetic discrimination by a school district in California. According to the allegations, in fall 2012 the Palo Alto Unified School District used genetic information regarding cystic fibrosis in deciding to transfer a student away from his neighborhood school to another school.

Genetic nondiscrimination laws are stronger in California than anywhere else in the United States. CalGINA (S.B. 559), which took effect five years ago, extended genetic nondiscrimination rights beyond the narrow scope of the federal statute known as GINA, the Genetic Information Nondiscrimination Act of 2008, which prohibits genetic discrimination in employment and health insurance contexts. However, this case was interesting to Genomics Law Report largely because the plaintiffs did not rely on CalGINA in their complaint against PAUSD but instead focused on protections against “perceived disability” provided under the Americans with Disabilities Act or ADA (42 U.S.C.A. §§12131 et seq.) and Section 504 of the Rehabilitation Act of 1973 (29 U.S.C.A. § 794). The school district had convinced a federal district court to dismiss the complaint, but the plaintiffs filed an appeal in January 2016.

• Previous coverage of CalGINA is available here
• Previous coverage of Chadam v. PAUSD is available here

What’s happened since the appeal was filed in January 2016?
The U.S. Court of Appeals for the Ninth Circuit heard arguments on October 19, 2016, and issued a decision on November 15, 2016. The court’s ruling overturned the district court’s dismissal of the ADA and Section 504 claims and remanded the case to the district court for further proceedings. While the court issued an unpublished judgment, which “is not precedent except as provided by Ninth Circuit Rule 36-3,” the plaintiffs’ attorney, Stephen R. Jaffe, publicly announced on LinkedIn that it was “a great victory for personal privacy.” The Ninth Circuit Court of Appeals is allowing the ADA and Section 504 genetic discrimination claims to move forward, all based on the student’s genetic information being a “perceived disability.”

The court made its decision by determining that the district court erred in two ways. The first error was the district court’s finding that there was a “direct threat” defense available under the facts presented in the complaint. The school district had argued that it made its decision out of concern for the health or safety of other students at the school who do have cystic fibrosis and that it had made a reasonable judgment that the student posed a “direct threat” to those other students. According to the Ninth Circuit, the error in allowing a direct threat defense was twofold: (1) such a defense requires an individual assessment of the threat but, as per the facts in the complaint (which must be taken as true in evaluating a motion to dismiss), no such individual assessment was made; and (2) the school district’s decision that the student posed a direct threat was contrary to “reasonable judgment” with “best available objective evidence.” The district court’s second error was finding that the plaintiff had not shown the requisite intent to establish a claim for discrimination. Establishing a claim for discrimination, the Court of Appeals noted in its decision, does not require the plaintiff to show “bad motive, will, or animosity” or even an intent to cause harm. Rather, the action or decision to exclude someone categorically (e.g., because of protected class status) is “facial discrimination” and sufficient, even if no harm or injury was intended.

The case moves forward
The Ninth Circuit’s rejection of the motion to dismiss means that the case is back on track toward eventual trial. There are no apparent signs that the school district will settle the case. On December 21, 2016, the school district’s attorneys filed an answer to the amended complaint and raised a litany of affirmative defenses, including:

• failure to state a claim,
• lack of jurisdiction,
• lack of intent,
• immunity,
• defendant acted in conformity with law,
• equity (e.g., unclean hands and equitable estoppel),
• res judicata,
• statute of limitations,
• lack of standing,
• waiver/release,
• remedies not supported by claims, and
• no damages attributable to the defendant.

The defendant did not provide any details about these affirmative defenses to explain how or why they might be applicable. Because some affirmative defenses can be waived if not asserted, it is reasonable to treat these defenses for the moment as mere boilerplate—that is, inserted as a matter of lawyerly self-protection.

The court has ordered mediation to resume before March 14, 2017 and has since appointed a mediator to the case.

Keep this case on your watch list
Courts have never directly acknowledged a person’s genotype or carrier status as sufficient to pursue a “perceived disability” claim under the ADA or Section 504 protections against discrimination. A plaintiff’s victory would clarify (at least for people who live in the Ninth Circuit—CA, WA, OR, ID, MT, NV, AZ, AK, and HI) that those who are victims of genetic discrimination in areas of society other than employment or health insurance (the areas covered by GINA) are not left unprotected by federal law and are able to seek remedies under the Americans with Disabilities Act and Section 504.

The case is an important reminder that even if the PAUSD’s actions were permissible under federal law, state law (CalGINA) applicable at the time and applicable today prohibits school districts in California from using genetic information to make decisions about its students. The PAUSD’s decision to continue defending this case signals one or both of two things. The first is that defense attorneys believe that they can successfully slam the door on a broad ADA precedent that would allow “perceived disability” claims against those who discriminate based on genetic information. That seems somewhat unlikely, given the willingness of the Ninth Circuit to allow the case to proceed and the strength of the facts alleged by the plaintiff’s attorneys. The second is that the school district is focused solely on the money—either trying to minimize the size of any settlement or court award or trying to make sure an insurer is responsible for covering the payment of that settlement or award. Perhaps the PAUSD is showing its willingness to roll the dice if a reasonable court award is perceived as having a good chance of being substantially lower than any settlement amounts under consideration.

There has been very little public discussion of the case since initial interest when the appeal was filed last year. The plaintiff’s case has now survived a motion to dismiss, but the case has yet to be decided on the merits. For genetic rights advocates, this case should remain high on the watch list in 2017 with the Ninth Circuit Court of Appeals poised to strengthen genetic nondiscrimination rights through ADA and Section 504 case law.

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Filed under Genomic Policymaking, Genomics & Medicine, Genomics & Society, Pending Litigation, Privacy

FDA Issues Guidance for Next Generation Sequencing

On July 8, 2016, the FDA issued draft guidance on the subject of next generation sequencing (NGS) activities: (1) “Uses of Standards in FDA Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases” and (2) “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics.” The first focuses on the FDA’s proposed use of standards to help establish the safety and efficacy of NGS-based tests. The second focuses on the importance of high quality and publicly accessible databases to provide robust scientific evidence for understanding genomic variation, to inform decision-making, and to assess the clinical validity of NGS-based tests. Guidance is not a formal regulation, but rather an agency’s statement about how it will interpret or apply a regulation in the future. Draft guidance is a proposed policy that means the agency is formulating a position, whereas a final guidance is a document that represents what the agency has settled on as its interpretive policy. In theory, guidance is intended to serve as additional instructions for complying with rules and not intended to serve as the rules themselves.

The premise underlying the draft guidance is the controversial and—as yet—legally untested assertion that genomic analyses of all kinds are “medical devices” that Congress has, by statute, authorized the FDA to regulate. If they are, then the FDA would have the power to bring them under its current risk-based classification scheme for medical devices or to create a new scheme for them. If they are not medical devices, then the effort to regulate them might exceed the FDA’s statutory authority and conceivably amount to an unconstitutional regulatory overreach. Both draft guidance documents avoid any mention of the overarching debate, a subject covered extensively on Genomics Law Report, surrounding FDA oversight of all laboratory developed tests (LDTs) and in vitro diagnostic multivariate index assays (IVDMIAs). As others have noted, it is impossible to consider these new pieces of draft guidance outside of that context. Nonetheless, even the FDA asserts (via Twitter and elsewhere) that the two new drafts are intended to facilitate the Precision Medicine Initiative (PMI) and are distinct from the agency’s expressed intention to regulate LDTs. These pieces of draft guidance also give a policy-based reason for pause, as they could be another example of governance by guidance, a highly problematic approach as highlighted recently by John Conley with regard to the HIPAA right to access lab data and results.
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Filed under Badges, Direct-to-Consumer Services, FDA LDT Regulation, General Interest, Genetic Testing/Screening, Genomic Sequencing, Genomics & Medicine, Genomics & Society, Legal & Regulatory, Pending Regulation

EU Adopts New Privacy Shield for Data Transfers to U.S.

Back in April, we reported on some new developments in European Union law that have implications for the life sciences industry. One of these developments was in the privacy area—the final approval of the EU’s new General Data Protection Regulation (GDPR). The GDPR will have enormous significance for medical research and practice, since it will govern the collection and use of health data related to EU citizens. This month has brought a complementary and equally significant development, this time dealing with the transfer of personal data—including health data—from the EU to the U.S.

On July 12, 2016, the European Union announced that it had formally adopted the long-awaited EU-U.S. Privacy Shield to permit the transfer of personal data from EU countries to the United States.
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Filed under International Developments, Privacy, Privacy, Privacy

The EEOC’s Final Rule on GINA and Employer-Sponsored Wellness Programs to Take Effect This Month

Gina name tagOn May 17, 2016, the Equal Employment Opportunity Commission (EEOC), which is the agency charged with enforcing Title II of the Genetic Information Nondiscrimination Act (GINA), issued a final rule changing how employers can set up incentives for the wellness programs they sponsor for their employees.

As previously reported on Genomics Law Report, on October 30, 2015 the EEOC had issued a proposed rule to amend the GINA regulations in an attempt to harmonize them with the Affordable Care Act’s promotion of employer wellness programs to lower health care costs. The EEOC indicated it had received more than 3000 public comments before the close of the comment period on January 28, 2016.

In short, the final rule allows employers to offer financial and in-kind incentives for an employee’s spouse to provide information about the spouse’s current or former health status as part of a health risk assessment in connection with a voluntary employer-sponsored wellness program so long as certain requirements are met.
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Filed under Genomic Policymaking, Genomics & Medicine, GINA, Legal & Regulatory, Privacy, Privacy, Privacy

Cleveland Clinic Pathologist Urges Contract Solution for Return of Genomic Data

The Cleveland Clinic’s Roger Klein responds to my previous GLR post:

Roger-Klein-MD-JDThe Office of Civil Rights’ interpretation of the requirements of 45 CFR § 164 could pose problems for clinical laboratories and the professionals who practice within them. Although the issue of providing benign variants for a single gene, at least prospectively, would be straightforward, a broad definition of the designated medical record set could result in considerable complexity when one considers large-scale sequencing. Some excluded data can be of variable reliability, may be prospectively filtered by software, or may otherwise be omitted from the patient report because of professional interpretation and judgment. One can legitimately argue that this interpretation and judgment, as reflected in the patient report, should serve as the gateway to the official medical record.
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Filed under Genetic Testing/Screening, Genomic Sequencing, Genomics & Medicine, Genomics & Society

UNC Geneticist Comments on Testing Laboratories’ Duty to Return Genomic Data to Patients

UNC’s Karen Weck responds to my previous GLR post:

I agree in principle that patients have the right to access their genomic data; however, in practice it is much more complicated (as things often are). Giving a patient his/her raw sequencing data would be meaningless – it is the interpretation of the clinical significance of sequence data that is important when reporting results. This latter requires the expertise of molecular genetic laboratorians and clinical geneticists. We do not return all genomic sequence variants to individuals in exome sequencing, for example when we determine that they are unlikely to be contributory to their disease or medical health. It is important to those of us doing this that we retain the ability to use our professional judgement to determine what should be reported to patients as medically relevant, primarily so as not to dilute important medical information with irrelevant information.

Karen E. Weck, MD
Professor of Pathology & Laboratory Medicine and Genetics
Director, Molecular Genetics
University of North Carolina at Chapel Hill

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Filed under Genetic Testing/Screening, Genomic Sequencing, Genomics & Society

ACLU v. Myriad Genetics, Round 2: The Problem of Governance-by-Guidance

MyriadJust about everyone interested enough in genomics and the law to read this post will know that the American Civil Liberties Union waged a long and ultimately successful legal campaign to invalidate Myriad Genetics’ patent claims to isolated BRCA genes, mutations of which are linked to breast and ovarian cancer. Now the ACLU has launched a second front, this time attacking Myriad’s post-patent business model of maintaining its vast and unique database of genotype-phenotype associations as a trade secret. GLR reported on that evolving strategy two years ago.

The new ACLU attack has, thus far, received modest attention in the scientific press, and some of what has been reported is inaccurate. In this post I will briefly review what has actually happened and then try to sort out fact from fiction in the reportage. The bottom line is that the federal government has not created new stealth regulations dealing with the disclosure of genomic data to patients. It has, however, used the practice of governance-by-guidance to make significant new policy, which is problematic enough in its own right.
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Filed under Genomic Policymaking, Genomics & Society, Myriad Gene Patent Litigation, Patent Litigation, Patents & IP, Pending Litigation

Litigating the Accountability of Clinical Genomics Laboratories

Seeking Accountability from Clinical Genomics Laboratories

A wrongful death case pending in a federal court in Columbia, SC—Williams v. Quest Diagnostics, Inc., et al.—demonstrates the very high stakes involved with clinical genomics testing. The case also underscores the ongoing struggle to (1) establish accountability when mistakes happen and (2) establish a reasonable and effective level of governmental oversight for the laboratories performing such tests. The case could have dramatic implications for the future practice of genomic medicine, and regardless of how this specific case ultimately plays out in the courtroom, the allegations should serve as a serious wake up call to those involved in genomics for clinical purposes in any way.
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Filed under General Interest, Genetic Testing/Screening, Genomics & Medicine, Legal & Regulatory, Pending Litigation