Will the Supreme Court’s decision in the Myriad case discourage innovation?

by Maeve Luthin, JD, Professional Development Manager

In June’s Association for Molecular Pathology v. Myriad Genetics, Inc. (Myriad) decision, the Supreme Court determined that human genes fall within the “laws of nature” exception to patentable material. This decision invalidated Myriad’s exclusive claim to BRCA 1 and BRCA 2 tests that can be used in determining a woman’s risk in contracting breast and ovarian cancer. However, Myriad wasn’t asserting a patent on the tests; its theory was that since it patented the genes, no one else had the right to use the genes in their research.

Contesting patent claims is a lengthy, expensive process that is usually avoided unless multiple deep-pocketed competitors are claiming the same patent, because if they prevail, they expect their profits to cover the cost of litigation (e.g., the Apple/Samsung trial last spring). Myriad was proactive and aggressive in asserting its patent claims and sending cease and desist orders to researchers, universities, and other entities engaged in the business of assessing the genetic risk for cancers associated with the BRCA 1 and BRCA 2 genes. It wasn’t until a group of physicians, patients, and others—frustrated by their inability to conduct testing through non-Myriad labs—banded together that the case was made its way to court.

Many people in the biomedical research community are predicting that this decision will help lower the cost of personalized medicine, making tests like the ones Myriad offers more financially accessible and easier for patients to obtain. However, if companies believe there is little incentive to enter into the research arena because of the loss of exclusivity in selling a product, prices cannot fall due to a lack of competition in the marketplace. The court tried to circumvent this problem by narrowing its ruling to only include human genes, thereby allowing applicants to seek method patents and patents that incorporate the knowledge gained by gene and mutation discovery.

This ruling reinforces the importance both public domain and private discovery have in human subjects research. In declaring that human genes cannot be monopolized by any one entity, the court guarantees researchers open access to genetic source material, thereby assuring a scenario in which multiple investigators can conduct research simultaneously, challenging one another to improve upon previous discoveries. Ideally, this would lead to discovering more mutations, more effective therapies, and better answers to critical clinical care questions faster than if a single corporation were to monopolize all research associated with a single gene.

By clearly stating that patents on novel methods, manipulated DNA, and new applications of knowledge gained by gene research constitutes patentable subject matter, the court recognized the importance of incentivizing scientific discovery. Investors are more likely to back expensive research when the possibility of profit exists; this is especially critical right now, with federal government spending on research at an all-time low. Additionally, the patent process balances the monopoly rights (generally twenty year periods) awarded to successful applicants with transparency. All patent applications are published in their entirety, including the section in which applicants describe how to create the patentable object. Though competitors are liable if they reverse engineer the patentable subject matter, that knowledge can still propel research forward.

Research Ethics Roundup: Unethical research unearthed in Canada, allegations of misconduct in China, and more

by Maeve Luthin, JD, Professional Development Manager

There’s never a summer lull in science! Whether you are at the office basking in air conditioned glory or on vacation soaking up some rays, catch up with the latest news in research ethics by reading this week’s Research Ethics Roundup.

Do Clinical Trials Work?: In this New York Times op-ed piece, Clifton Leaf explores the high failure rate of randomized, controlled phase III clinical trials and their inability to provide investigators with information on why a drug may work for some patients but not others. Clifton explains that many companies are now designing smaller trials that recruit subjects who have particular genetic or molecular signatures and will produce results that will allow researchers to better understand why a drug may be effective.

Hungry Aboriginal Children, Adults Used as Nutritional Test Subjects: University of Guelph researcher Ian Mosby uncovered documents that revealed a long-standing, post-World War II nutritional experiment conducted by the Canadian government on malnourished aboriginal children living on remote reservations. The children involved were not told that they were participating in the study, which was to better understand the role of vitamins and minerals in a healthy diet. Some schools depressed milk rations, others used enriched flour that could not be sold legally in Canada, and others withdrew dental services. At the time of the study, guidelines for research with human subjects were just being developed.

Drug Research in China Falls Under a Cloud: An internal GlaxoSmithKline audit obtained by the New York Times reveals possible misconduct at its Shanghai research and development center. Improper clinical trial monitoring, inadequate consent documentation, bribery allegations, and failure to report the results of animal studies before beginning human trials are among the concerns raised in the report.

Opposition to NIH Chimp Plan: Chris Abee, director of MD Anderson’s animal research facility, expresses his opposition to the National Institute of Health’s plan to retire most chimpanzees used in federally-funded research. Abee argues that MD Anderson can provide better care and treatment for its chimps than Chimp Haven, the federal facility in Louisiana to which the chimps will eventually retire. The chimps at MD Anderson are currently the subjects of observational studies on aging, although some were subjects of a previous hepatitis C study.

Genetic Advance in Down’s Syndrome: University of Massachusetts Medical School researchers have “silenced” the extra copies of the chromosome that causes the symptoms of Down’s syndrome. This development will allow scientists to study the cellular basis for the condition, opening the possibility that further research could lead to genetic therapy. However, as the team explained, it could take decades of research before the findings translate to any clinical application.

Respond in a calm, professional manner: An interview with Kristen Kenney

Welcome to another installment of our featured member interviews where we introduce you to PRIM&R’s members—individuals who work to advance ethical research on a daily basis. Please read on to learn more about their professional experiences, how membership helps connect them to a larger community, and what goes on behind-the-scenes in their lives!

Today we’d like to introduce you to Kristen Kenney, assistant director, Office of Research Integrity and Compliance at Children’s Hospital of Chicago in Chicago, IL.  

Megan Frame (MF): When and why did you join the field? 
Kristen Kenney (KK): I graduated with a degree in veterinary technology from Michigan State University (GO GREEN!). I began working in research as an assistant scientist at a pharmaceutical company in 2002. In 2008, I made the transition from working with animals to research administration and compliance. This seemed like a natural transition as I was able to blend my respect for animals and my experience as a scientist, and I found the perfect job for me: IACUC administration!

MF: What skills are particularly helpful in a job like yours?
KK: Having an open mind to other perspectives, experience in performing research with animals prior to working in research administration, and organization.

MF: Tell us about one or more article, book, or document that has influenced your professional life. 
KK: After reading All Creatures Great and Small by James Herriot at a young age, I was convinced that I wanted to work with animals. Dr. Herriot’s adventures as a veterinarian sounded exciting and rewarding, and although I did not end up with a career as a veterinarian, having the motivation to care for animals eventually led me to where I am today. I am happy to be in a position that oversees the protection of animals used in research.

MF: Have there been any PRIM&R events or talks that you have attended that have significantly impacted your approach to your work? If so, what were they and how did they influence you?
KK: Recently, I attended panel discussion on Practical Strategies for Conducting Harm/Benefit Analysis of Animal Research at the 2013 Institutional Animal Care and Use Committee (IACUC) Conference. I appreciated the various viewpoints represented during this discussion, and in particular, Dr. Allyson Bennett’s perspective as a principal investigator. She presented a well-balanced approach to reviewing animal protocols and reminded the group to look at the possible long term benefits of a specific project. Naturally, I tend to look at the immediate impact a procedure may have on the welfare of the animal. Hearing Dr. Bennett speak reminded me to consider the overall picture when it comes to research.

MF: What advice have you found most helpful in your career? 
KK: I’ve learned there is a difference between responding to a situation and reacting to a situation. Responding in a calm, professional manner always leads to the best outcome.

Thank you for being part of the membership community and sharing your story, Kristen. We hope to see you next year at the 2014 IACUC Conference in Denver, CO!

If you’d like to learn more about becoming a member, please visit our website today. 

Publishing clinical trial data: The who, what, when, where, and why

by Joan Rachlin, JD, MPH, Executive Director

Among the many topics that will be presented and discussed at the 2013 Advancing Ethical Research Conference is the ubiquitous issue of data transparency. Some of the most hotly debated questions making the research ethics rounds include who should interpret, distribute, review, and receive data, and with good reason. From WikiLeaks to National Security Agency (NSA) whistleblowers, and all other manner and form of data breaches, the problems of data privacy, data security, data accuracy, and data availability are ones that won’t go away any time soon.

I recently read a piece in The New York Times about Peter Doshi, PhD, a 32-year-old post-doctoral fellow at Johns Hopkins University, who has been pressing pharmaceutical companies to make their clinical trial data public. Dr. Doshi contends that the financial conflicts of interest that permeate considerable segments of biomedical research, as well as the publication bias of journals, make public disclosure necessary so that consumers and patients can participate more fully in making decisions regarding their care. It is well-documented that only half of all clinical trials are published, and that negative results, which are at least as instructive as positive ones, rarely see the light of day.

Although one can hardly imagine a more David-and-Goliath-like match, Dr. Doshi and his allies have made some inroads, most notably in helping to persuade GlaxoSmithKline to agree to share detailed data from all global clinical trials conducted during the past thirteen years, though nothing has yet been released.

Dr. Doshi and his colleagues’ quest for clinical trial transparency began while they were trying to determine whether or not Tamiflu, manufactured by Roche, was an effective treatment for flu; this pursuit proved difficult because the bulk of the data on which claims about Tamiflu’s efficacy had been based was unavailable. Only two out of ten Tamiflu trials, it turned out, had been fully published, and when scientists at the Cochrane Collaboration, a well-respected network of independent researchers working with Dr. Doshi, tried to track down the other eight, they hit repeated road blocks. The Cochrane Collaboration determined that, as a result of the incomplete picture Roche presented about Tamiflu, they could not endorse its effectiveness. Only then did Roche begin to open its file cabinets, but the issue of Tamiflu’s value in reducing flu symptoms has still not been resolved. However, Roche has joined GlaxoSmithKline in agreeing to share detailed data with outside researchers.

This breakthrough, especially when combined with the European Medicines Agency’s proposal to require wider access to trial, has fueled public demand for information that has formerly been entirely within the province of researchers, clinicians, and journal editors. The Pharmaceutical Research and Manufacturers of America, as well as most drug companies—excluding GlaxoSmithKline and Roche—have opposed this push. Some argue that American consumers already have access to raw data via the federal clearinghouse ClinicalTrials.gov, but there are extensive limitations placed on what kinds of information can be released through that medium.

The New York Times article ends with a powerful and provocative summary of Dr. Doshi’s current message to the drug companies: “publish your data, or we’ll do it for you.”

And there are many other cases fueling the call for requiring data publication. On June 17, for example, two independent reports were issued, indicating that Medtronic’s spinal surgery product, Infuse, carried with it serious risks, including cancer and male infertility, and that there was no demonstrated improvement over already-existing products for the same purpose. The reports, prepared under the auspices of Yale University with funding from Medtronic, reviewed 17 studies. The news reports surrounding these revelations are rife with allegations that negative data was suppressed, that conflicts of interest abounded, and that Medtronics promoted off-label use.

These issues around data transparency and review, among so many others that are rapidly changing the research landscape, will be front and center at the 2013 AER Conference, which will be held November 7-9 in Boston, MA. I hope you will join us there for what promises to be an educational odyssey like none other.

In research on standard of care interventions, when and to what extent does randomization itself pose foreseeable risks?

by Elisa A. Hurley, PhD, Education Director

Those who have been following the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) controversy know that the story has continued to unfold over the past month. Here I review several of the latest developments, some of which may have wide implications for the human research protections community.

Three weeks after the New England Journal of Medicine (NEJM) published a letter to the editor signed by 46 prominent bioethicists, which called for the Office for Human Research Protections (OHRP) to retract its determination letter to the University of Alabama at Birmingham (UAB), the NEJM posted a second letter, signed by a group of 45 high-profile bioethicists, that stated their agreement with OHRP’s original determination that “the informed-consent documents that were used in … SUPPORT were seriously inadequate” because they failed to appropriately describe the purpose of the research, the research procedures, the foreseeable risks, and the relevant alternatives to study participation.

The authors of this second letter further criticize the statement, included in about half the SUPPORT sites’ consent forms, that because all the treatments proposed in the study were standard of care, there was no foreseeable increase in risk:  “The potential risks and benefits of being in the study could not be said to be the same as the potential risks and benefits of receiving care outside the study, in settings in which infants were not randomly assigned and held to an oxygen level at either end of a wider range of oxygen-saturation levels generally considered to be safe.”

That very same day, making good on a promise in OHRP’s June 4 letter to UAB, the Department of Health and Human Services (DHHS) announced  that it will hold a public meeting on August 28 to gather input for shaping guidance about how to apply the federal regulations governing randomized human subjects research to studies on standard of care interventions. The announcement also invites the submission of written public comments by September 9 “regarding how an IRB should assess the risk of research involving randomization to one or more treatments within the standard of care for particular interventions, and what reasonably foreseeable risks of the research should be disclosed to research subjects in the informed consent process.” The notice then outlines five specific questions on which DHHS is seeking public guidance.

The SUPPORT study has generated heated discussion about everything from the definitions of forseeable risk and clinical equipoise, to the proper purview of OHRP, to who gets to count as a bioethicist. It’s easy to become bewildered and overwhelmed by all that has been said by those with strong views on both sides, especially when the disagreements seem to extend to some of the crucial facts around SUPPORT, including, for instance, whether the increased mortality rate at the lower ends of the oxygenation range was a foreseeable risk, and how much tailoring of oxygen levels to individual needs is involved in the standard of care for extremely premature infants.

What has emerged, however, as a core question raised by the SUPPORT study is: When we are talking about research on standard of care, when and to what extent does randomization itself pose foreseeable risks that then must be disclosed in the informed consent process? PRIM&R encourages all those within the research protections community to share their input on this question with DHHS and thereby take advantage of this important opportunity to shape future guidance for the growing domain of comparative effectiveness research.

Research Ethics Roundup: The launch of a new accreditation service, clinical trial transparency, and more

by Maeve Luthin, JD, Professional Development Manager

Catch up on the events of the past two weeks in the research ethics world! Whether you read this edition right away or save the stories for later, spend some time learning about what your colleagues have been up to.

Unlikely Partners: The New York Times details the movement that led National Institutes of Health director Francis Collins, MD, PhD, to commission the Institute of Medicine’s (IOM’s) study on the use of chimpanzees in biomedical research, which recommended that chimps should be used only in cases necessary for human health. Last month, Collins accepted a working group’s recommendations regarding how to implement the IOM report, including the retirement of all but about 50 chimps from research.

Alion Launches HRPP Accreditation Services: Alion Science and Technology announced the launch of Alion Human Research Protection Program Accreditation Services, which will provide accreditation for organizations involved in conducting, managing, or reviewing research involving human subjects.

Father’s Genetic Quest Pays Off: Frustrated by doctors’ inability to diagnose his daughter Bea, Hugh Rienhoff, a geneticist-turned-biotech entrepreneur, bought his own lab equipment to sequence family members’ DNA. After finding the gene mutation, the Reinhoff family became a test group for exome sequencing, a procedure that pinpointed the faulty sequence responsible for Bea’s condition.

Breaking the Seal on Drug Research: While the European Medicines Agency considers a proposal to make all clinical trial data public when a drug is approved in the European Union, many pharmaceutical companies are reviewing their own transparency policies, including GlaxoSmithKline, which pledged to release all clinical trial data from the past thirteen years. These changes come at a time when new questions about publication bias have arisen, prompting outside researchers to re-analyze study data to determine whether published results underreport complications or mislead readers as to the efficacy of drugs.

Unverified Science: The inability to reproduce published findings of pre-clinical studies drives up the cost of research as valuable time and money are used to re-create research findings instead of being used to drive new discoveries.

Open and respectful dialogue on the use of animals in research is essential

by Joan Rachlin JD, MPH, Executive Director

A violent new video game from People for the Ethical Treatment of Animals (PETA) is the latest entry in the polarizing, emotion-laden debate surrounding animal research. The game, Cage Fight, allows players to assume the role of one of three famous mixed martial arts fighters as they attempt to free animals and take on researchers in a university lab, military installation, and pharmaceutical company lab.

The game first opens in a lab at fictitious River City University, where players see a grisly scene that includes blood splattered walls, animals in woefully undersized cages, and a cleaver-wielding scientist. The accompanying text, which is displayed across the bottom of the screen, reads, “Science Lab – Cruelty to Animals in Progress.” Accompanying this brutal backdrop is equally offensive dialogue:

Professor Podesta: You’re not allowed in here. You can’t see this!
Jake: Too late—I’ve recorded you torturing that cat!
Professor Podesta: But I have to publish studies in order to keep my job and the easiest way is to lock up animals and cripple them.
Jake: You won’t have a job when people see the truth.
Professor Podesta: I’ll treat you to the same fate as this cat before I let you share that video! Off with your head!

From there, players progress by kicking and punching the researchers they encounter, despite the game’s obligatory disclaimer that it is illegal to do so in real life. The freeing of the animals, however, remains an optional endeavor. In a press release, PETA director of marketing innovations, Joel Bartlett, noted that “Cage Fight doesn’t just show you how animals suffer in laboratories—it gives you the chance to combat cruel animal experimenters, both in the game and in real life.”

As the quote above suggests, the connection to real life that the “game” establishes is far from tenuous: From the very first screen players are encouraged to take action. They are reminded that they can and should mount a legal “assault against animal experimentation in real life… by taking action on PETA’s action alerts.” In fact, on the very same page that hosts Cage Fight, players are told that “animals abused in laboratories in real life need [their] help,” and they are asked to send email the National Institutes of Health to put a stop to research being conducted at the University of Wisconsin-Madison.

In this context, referring to Cage Fight as simply a game seems unfair. Cage Fight sends a dangerous message to those who play it regarding how one should respond when disagreements arise on complicated issues, while contravening PETA’s representation that it “maintains a creed of nonviolence and does not advocate actions in which anyone, human or nonhuman, is injured.”

The promotion of violence as a tool in handling disagreements is particularly disheartening, and seems hypocritical coming from an organization that cries foul when they have concerns about the manner in which lab animals are treated. We can only infer that PETA feels no shame in bringing the force of its activism to bear when they allege—rightly or wrongly—that animals experience pain or suffering in a given setting, but that it’s perfectly fine to create a videogame that encourages the infliction of pain or suffering on researchers, with only the disclaimer referred to above as a half-hearted hedge. Videos such as Cage Fight are violent and advocate injury to humans, so where is PETA’s integrity in saying one thing but doing another?

PRIM&R has always ardently supported an open and respectful dialogue on the use of animals in research at its annual Institutional Animal Care and Use Committee (IACUC) Conferences. Toward that end we have encouraged participation from representatives of PETA, the Animal Welfare Institute, the Humane Society of the United States, and several other animal rights organizations over the years. I am among the many PRIM&R proponents of this effort to create a diverse and inclusive forum, believing that constructive, honest, and temperate exchanges among parties holding disparate views is among the best ways to erase distrust and help promote understanding.

Unfortunately, there is nothing about Cage Fight that is constructive, honest, or temperate. This latest entry from PETA reflects their blatantly inaccurate vision of animal research. They fail to see animal researchers as anything other than sinister, secretive, and cruel. By selecting a medium that encourages participation by children and others in real life action, PETA does not walk its talk about “[maintaining] a creed of nonviolence,” but rather manipulates players into thinking about only one very distorted side of an issue.

I believe both the research and the animal rights communities have a moral responsibility to encourage and participate in a fact-based dialogue, so that individuals can make their own informed decisions regarding animal research. The public is entitled to a clear and accurate understanding of the value of animal research to human and animal health, how that research is conducted, and the multiple layers of regulations that are in place to ensure the responsible care and use of laboratory animals. Young audiences to whom Cage Fight is directed are especially owed a clear, balanced, and accurate statement of the how and why animal research is conducted, as they are impressionable and can thus more easily fall prey to distortions.

The research and animal care and use communities must transform this latest assault on truth into an opportunity to educate the public about the facts. (A great resource for thoughtful, responsible, and reliable animal research information can be found on Speaking of Research’s blog.) I’ve heard it said that many people prefer a simple lie to the complicated truth, but the truth in this area is not so complicated. It does, though, require that you—members of the research and animal care communities—redouble your efforts to share what it is you do, how you do it, and why it matters.