By Paul Nicolaus

December 13, 2016 | Cancer patients don’t care about consent. They care about getting better.

That’s the way Bryce Olson sees it, anyway. Diagnosed in 2014 with aggressive prostate cancer at the age of 45, the global marketing director for the Health & Life Sciences Group at Intel Corporation has a vantage point that has emerged from first-hand experience.

“I went through the standard of care,” he said. “I did chemo. I did surgery. And none of that worked.” Although the chemo allowed him about nine months of progression-free survival, it also came with a hefty price. “I had to pay for that with months of chemo and being sick from it, and I still have side effects today.” 

Fortunately for Olson, he happens to work for a company at the forefront of genomics and precision medicine. “We’re the chips that are inside of your notebook or your desktop,” he said. “We’re also inside of genomic sequencers.” And according to him, the company creates processors that fuel 98% of all servers in data centers today.

Learning about all of Intel’s involvements in this realm initially proved fascinating for Olson. He became aware of efforts at the Translational Genomics Research Institute (TGen), for example, which handled the first pediatric precision medicine cancer trial for kids with neuroblastoma.

Genomic sequencing was used to understand what was occurring at the DNA level, and care progressed from biopsy to a target treatment plan within just 12 days. This speedy timeline enabled the ability to stay ahead of this form of fast-growing cancer and put many of the kids in remission.

After hearing of this and similar successes, Olson’s excitement turned to frustration. “I got really pissed off, to be honest with you, because my own care team wasn’t telling me about this,” he said.

Eventually, he demanded the sequencing of his own tumor and soon found out that his cancer was progressing along a mutated pathway. Because the standard of care wasn’t targeting that mutation, he searched out and found a phase one clinical trial testing a new inhibitor designed to block cancer along that particular pathway.

“I called up the people at the clinical trial and I said, ‘I want in,’” Olson recalled.

Although his request was met with resistance, when Olson explained that he already had his sequencing data and could prove that he was a molecular match for the drug being tested, that resistance faded.

“So long story short, I get in, I get evaluated, and they accept me,” he said. “I start the drug, and I shut my cancer down for 18 months now.”

New Era of Medicine

Armed with a fresh perspective, Olson looks at the current state of medicine as a cycle of inaction. It begins with patients, most of whom are simply not aware of genomic sequencing. Because doctors aren’t asked about it, they typically don’t offer it, Olson said. They’re too busy just trying to keep up with standard of care. 

Meanwhile, the pharmaceutical industry is coming up with targeted drugs, but don’t have the sequencing data available to build large cohorts. And the payers are in no hurry to reimburse for this form of care because they don’t have solid evidence that it works. Top it all off with the policy side things, where patient consent is a hurdle that is slowing progress down.

If his cancer starts to progress again, Olson said he intends to take his genome and post it on Facebook. “That’s how much I want research to be able to have access to my genomic data so they can advance the science,” he said.

“If there’s a way I could give universal consent or some kind of machine readable consent, I’d sign up right now,” he said, “and I think, honestly, all advanced cancer patients would feel the same way if they knew that the genomic sequencing data that might be available for them could be used for the greater good to advance science.”

Olson is speaking from the perspective of someone who is, by his own admission, desperate for scientific progress. The phase one clinical trial drug that seems to have saved him likely won’t be approved by the FDA for years at this point, and if his cancer starts growing again he will drift “even further into no-man’s land.”

But he maintains a big picture view. A recent study in the British Journal of Cancer estimates that over one half of adults born since 1960 will be diagnosed with cancer at some point in their lifetimes, he pointed out, so there is a clear need to speed things up and move further into the realm of precision medicine for the sake of humanity.

“The standard of care for cancer today doesn’t really work, especially if you have advanced cancer,” Olson said. “If you’re just giving everyone the standard of care then it’s the same thing as throwing darts at a dartboard, the same thing as spinning the wheel in trial and error medicine.”

Some of the treatments developed decades—or more—ago are still being used, he added, noting that the Romans were trying to cut cancer out of people. The old standbys—chemo, radiation, surgery—just aren’t doing the job. “Genomics opens the door to being able to treat cancer differently,” he said, “and being able to really offer something more targeted that is less caustic and more effective.”

More Data Needed

Take a look at the Dana-Farber Cancer Institute, Olson said, where every cancer patient who walks through the door can opt to have their tumor sequenced. These types of large academic cancer centers are assembling massive genomic patient datasets because they are aware that this is the new way to treat cancer.

But that’s not enough, he warned. The thing about cancer is that no single institution can solve the problem. Even if Memorial Sloan Kettering, the largest cancer center in the U.S., sequenced their every patient, it would still only amount to 1% of the U.S. cancer population.

In order to address this issue of scale, Intel—prompted by the NCI’s Cloud Pilot competition—developed a Collaborative Cancer Cloud that allows cancer researchers to exchange healthcare information. Oregon Health & Science University, the Ontario Institute for Cancer Research, and the Dana-Farber Cancer Institute have all joined the initiative.

“We’ve responded by creating this collaborative cancer product,” he said. “If I’m a cancer institute, and I’m starting to sequence more and more of my cancer patients, I’m amassing this large dataset, but I [will still] never have enough information, especially for rare cancers.”

If a larger collaborative network can be tapped into in order to share molecular, treatment, and outcome data and do so in a way that preserves the privacy of the patients as well as intellectual property, then everybody wins.

“Cancer patients want and desperately need research to make more advancements and more discoveries, and that means they need access to more data,” he said. “I don’t think consent should get in the way.”

Olson hopes to see the development of a one-time, universal consent that would take data gleaned from any patient who has their genome sequenced for cancer or to participate in a clinical trial and make it available to any cancer researchers, as long as they’re using it to help generate new discoveries for the greater good of society.

“Consent is one of those areas that we just need to figure out because [researchers] all want to share, we all need to share, and companies like mine are creating the technology platforms that will enable them to share,” he said. “Policy can’t be the thing that prevents science from happening.”

Ethical and Legal Dilemmas

While Dr. Liz Worthey is also excited by the vast potential of genomics and believes in the need to continue to move further in the direction of scientific progress, her take on consent differs from Olson’s, leaning further in the direction of caution.

The director of informatics at the HudsonAlpha Institute for Biotechnology emphasized the wide range of highly complicated moral, ethical, and legal dilemmas involved along with the need to handle these issues with care.

From Worthey’s vantage point, the fact that the consent process is lengthy and somewhat difficult is actually a good thing, and working diligently to ensure that people buy in and fully understand the implications of consent is more crucial than moving full steam ahead. “Not everybody shares [my] opinion,” she said, “but I definitely think we need to err on that side.”

Thanks to technological advances, it is now cheaper and easier than ever to sequence and interpret genomic information. As technologies and tools progress, our understanding of the effect of genomic variants on disease continues to grow, and so does the sheer amount of data being generated.

The surface is just being scratched in terms of how these datasets could be mined and used for research that can continue to improve upon the clinical benefits for patients, but all this progress relies on the contributions of research participants. And therein lies the rub. As the field moves forward in leaps and bounds, new risks and exposures have emerged as well.

“When you extract genomic information it extracts it for everyone in your family that you’re genetically related to,” Worthey explained, “and because of that it requires a much more in-depth discussion of the complexities around doing that sort of research. People really have to have a better understanding of what might happen to that data because it’s not just their data. It’s also their third cousins’ and fifth cousins’ data as well.”

When someone without a genetic disease discovers their risk of developing an illness it comes along with plenty of uncertainty, and it’s never truly known just how that risk will actually play out. It is possible, too, to discover something about a person that relates to their religion or culture that may be sensitive or that an individual would simply not want to have shared or discovered.

While Olson is aware of the potential downsides, he reiterates his main claim: “I’m telling you, cancer patients don’t care. They just want to be saved.” He does acknowledge, however, that there are scenarios outside the realm of cancer where these downsides can be a significant concern.

Imagine newborns in the NICU struggling from a chromosomal abnormality or developmental disorder and the parents have no idea what’s going on. The concern might be that, while performing whole genome sequencing, you gain access to data that predicts a predisposition to other conditions beyond the disease in question.

“That, I think, is the danger,” he said. “When you do whole genome sequencing on an infant, the data could predict a lot about them that they may not want to know, that they may not want anyone else to know about, and it could make them vulnerable for employment in the future if it somehow got leaked that they had a predisposition to a certain disease.”

Those types of what-if scenarios could be incredibly far-reaching, as Worthey pointed out. Imagine, for example, a presidential candidate known to be predisposed to a disease like Alzheimer’s.

To date, federal laws such as the Federal Policy for the Protection of Human Subjects (a.k.a. the Common Rule), the Health Insurance Portability and Accountability Act (HIPAA), and the Genetic Information and Nondiscrimination Act (GINA) have attempted to find an appropriate balance between scientific progress and patient protection, but as the field of genomics continues to evolve the conversation continues.

GINA’s protections have gone part of the way, for example, but haven’t fully protected individuals from the denial of life insurance or long-term disability coverage based on genomic data, Worthey said.

And changes to the Common Rule, which was first published in 1991, have been proposed that are intended to enhance protections for human subjects, although the final alterations and the ways in which these could impact informed consent aren’t entirely clear at the moment.

Gathering Consent

Generally, the consent process consists of two phases, which can occur during the same meeting or on separate occasions. The first part is the educational component, and the second involves reviewing consent forms and signing the document.

The process provides information about a research project or clinical trial that will help individuals make voluntary, informed decisions about whether to begin or continue participating. The first part is normally carried out face to face, Worthey said, but with some of larger projects online videos or phone discussions are common.

“[The process is] designed to make sure that that person really understands both the strengths and the potential weaknesses of the [study] approach and also to make sure that they fully understand what might happen to their data,” she said.

There’s a lot of effort that goes into ensuring that consent documents uses language that is simple and clear, she explained, and there are steps that can be taken to address potential comprehension issues. If there is a language barrier, for example, it is important that there is adequate translation available.

In some cases, patients consent to be recontacted so that researchers have the ability to check back on the status of their disease years later. Many consents—perhaps all of them—include a clause that enables the ability to withdraw consent at a later date, Worthey explained. If someone no longer wishes to be part of a study, they can request that their data be expunged from the system. Normally this means their data comes out in all of its forms, but if it has already gone on to become part of an analysis used to produce additional data then it remains under the assumption that it is metadata no longer associated with that particular individual.

Differing Methods

Notably, the process does vary. “Consent has always been done differently at different places and done well at lots of places—just not the same,” Worthey said.

In some cases, an individual consents to use their data solely for the purpose of the study of a certain disorder, and in some cases there are specifics about who can make use of the data. While the specifics can vary, the material discussed and the intention behind it is generally very similar, she said.

Even so, there are at least a dozen different organizations that are putting out differing sets of guidelines. This includes entities like the FDA and the NIH, as well as the governing bodies of the individuals involved in the research, such as the American College of Medical Geneticists and the American Society of Human Genetics.

“All of them are trying to move forward to define what the right consent looks like, but I think the field is in kind of a flux,” she said. “We’re learning how to do it, I think it’s fair to say.”

Worthey points to the evolution of consent for NIH projects as one example of the way in which consent has moved toward a more uniform process over time. All of the sites involved in the Clinical Sequencing Exploratory Research (CSER) program were able to handle their own consent process, and each one was unique.

Fast forward a couple of years to the Undiagnosed Diseases Network (UDN). One of the goals of this project was to have every single site use the same consent documentation and enrollment process.

Revolutionizing Research

Ultimately, the real opportunity of genomics—and Worthey believes it will come true—is to be able to gather enough data to tackle a variety of the more common diseases that up until now we just haven’t been able to. “I think this is a thing that is going to help a lot of people,” she said. “It’s going to revolutionize research and medicine. I really believe that.”

While the scientific community learns how to best deal with the complexities of consent in order to get there, Worthey hopes this same community will do a good job of helping the masses see and understand the benefit of performing research so that more and more people become more and more willing to put their data into the mix.

“Society should move toward that,” she said, “and the way to do that is to educate people about the pros and cons, be very open and clear, and educate people about science in general a bit better. Tell them that this is an investment for society.”

Paul Nicolaus is a freelance writer specializing in health and medicine. Learn more at www.nicolauswriting.com.