Inaccurate direct-to-consumer raw genetic data can harm patients, new research suggests

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Whether or not you’ve ever had genetic testing, you probably know someone that has. Millions of people each year have their DNA analyzed by companies like 23andMe and Ancestry.com, seeking out personalized information about their heritage, health and other traits.

“The general public is excited about genetics because it can tell us a lot about our past ancestry and, if the right technology is used, about our future­­ ­— such as the likelihood of developing certain health problems,” said Tia Moscarello, a genetic counselor with Stanford’s Center for Inherited Cardiovascular Disease. “These tests are popular for good reason: many people want to be proactive about their health without spending a lot of money or making a trip to the doctor’s office to do it.”

Typically, these direct-to-consumer (DTC) genetic tests are less expensive than more comprehensive, clinical-grade genetic tests obtained through a health care provider.

However, the Food and Drug Administration limits what these companies can say about a consumer’s health. So many people download their raw genetic data obtained from the company, and then upload it to another company’s website for additional interpretation. But their raw data come with a disclaimer stating the information is not validated for accuracy nor intended for medical use.

“To our understanding, raw genetic data doesn’t go through quality control. We and the DTC labs know that raw data may not be accurate,” Moscarello said. For instance, a small study recently showed that 40 percent of genetic variants identified in direct-to-consumer raw data and sent for clinical confirmation were false positives — meaning that the genetic variants weren’t really present.

Moscarello has personally witnessed the impact of these false positives on patients and their families. In a recent commentary in Genetics in Medicine, she and her colleagues describe two cases of false positives seen at Stanford and two more seen at other institutions. These patients received raw data with genetic variants known to be associated with inherited heart conditions that would predispose them to sudden death, she said. Fortunately, a clinical lab determined that the results were incorrect.

Moscarello said she and her co-authors wrote the commentary to call attention to the potential harms of direct-to-consumer raw data interpretation, which extend beyond the potential for inaccurate results. She explained:

“Finding out that you or a family member are at risk for an inherited heart condition can be a very emotional, life-changing event. To go through that without an expert to talk to, or perhaps without support systems nearby, was challenging for our patients. They had to wait for an appointment with a genetic counselor who could explain the test and its limitations, and to provide support. That is usually provided prior to genetic testing, so patients can decide if they would like to proceed.”

The commentary also discussed the impact that DTC testing is having on the health care system.  For the four cases, this burden included the time and expense of four clinical-grade genetic tests, several echocardiograms and electrocardiograms for each patient, multiple visits with physician specialists, an MRI, and the implant and subsequent explant of an implantable cardioverter defibrillator, Moscarello said.

So what can be done?  The authors call for more research to determine the frequency and impact of people being affected by false positives in their raw genetic data interpretations. When a result with potential clinical significance is found, they recommend that it be sent for confirmation to a clinical-grade lab. This should occur before the consumer has to undergo costly clinical evaluations and tests, she said, concluding:

“It is clear that DTC genetic testing is here to stay, and for good reason. So it’s important to focus on maximizing the benefits of such large-scale, clinician-free testing, while minimizing the harms to consumers.

Collaboration between clinicians, consumers and the DTC genetic testing companies is a priority. I hope that DTC genetic testing companies will work with clinical genetics experts to create educational resources — so that consumers and non-specialist physicians know the data may be inaccurate, and what to do next if something is found.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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Community cooperation following disasters key to recovery, Stanford study finds

Photo of Norway by Vidar Nordli-Mathisen

Why are some communities resilient in the face of disasters such as epidemics, while others struggle to recover? You might think it is driven by the availability of economic resources, but a new study shows that community cooperation — admittedly challenging in the face of an infectious disease — is the key.

Recently published in Academy of Management Journal, the study led by Hayagreeva Rao, PhD, a Stanford Business professor, found that a community’s resilience primarily depends on two factors:

  • whether the cause of the disaster is attributed to other community members or an act of nature; and
  • whether the community includes diverse organizations that encourage collaboration.

The researchers analyzed and compared two well-documented disasters that occurred in Norway in the early 1900s: an outbreak of the highly-contagious Spanish flu that caused many fatalities, and a severe spring frost that led to economic hardship for the predominantly farming community.

They found that disasters attributed to other community members — like contagious epidemics — weakened cooperation, increased distrust and led to a long-term reduction in organization building. By contrast, disasters attributed to an act of nature evoked a sense of shared fate that fostered cooperation.

Rao and colleague Henrich Greve, PhD, a professor of entrepreneurship at INSEAD, explained in the paper:

“The typical response to pandemics includes isolation and treatment, home quarantines, closure of schools, cancellation of large-scale public meetings, and other steps to reduce social density. While these immediate responses are entirely practical, policy planners should also consider how a pandemic impairs the social infrastructure of a community over the long term, and undertake initiatives to foster the building of community organizations.”

For instance, the Spanish flu impaired the Norwegian communities from building new community organizations for 25 years, they wrote.

In contrast, Norway’s farming families pulled together when faced with natural agricultural disasters — motivating them to form retail cooperatives, mutual insurance organizations and savings banks to help share risk.

The researchers determined that successful disaster recovery also hinged on the existing social infrastructure: a community with diverse and cooperative voluntary organizations more effectively responded.

“The better the infrastructure, the better the recovery,” said Rao in a recent Stanford Business news piece. “A disaster is a shock. Think of those organizations as the shock absorbers.”

In the paper, they offered an example. In the 1995 heat wave in Chicago, which led to far fewer deaths in a Latino neighborhood than in an adjacent African-American neighborhood. This was because the sheer variety of Latino neighborhood organizations created overlapping networks that allowed people to check on the elderly, they wrote.

The authors concluded with a call for more research on the effect of climate-related disasters like floods and droughts. We need to know how these impact the birth and sustainability of community volunteer organizations, they said.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Nicotine patches and medications aren’t enough to quit smoking, a study finds

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I’ve watched family members and friends struggle to quit smoking, using nicotine patches and prescription medications. For many, it continues to be an ongoing battle.

This struggle is common, according to a new study from the University of California, San Diego that shows using smoking cessation drugs alone may not improve your chances of successfully quitting. The researchers studied two patient groups — comparing patients who used medication aids to ones that did not — to evaluate the effectiveness of three frontline smoking cessation drugs. To learn more, I spoke with the lead author Eric Leas, PhD, who conducted the research as a graduate student at UC San Diego and is now a postdoc at Stanford School of Medicine.

What inspired you to study the effectiveness of smoking cessation drugs?

“There is a major public health need for smoking cessation aids. Tobacco use remains the primary cause of cancer and cancer mortality in the United States and quitting smoking is so difficult for many smokers. I have several close family members and friends who have had debilitating disease caused by smoking and who struggled for many years to quit.

Several randomized trials have shown that some pharmaceutical smoking cessation aids can double quit rates. However, in the early 2000s, post-market surveillance studies of these cessation aids suggested that the population effectiveness did not match the randomized trial results. This was a major surprise to the medical field and met with some opposition. A criticism of these surveillance studies was that the same individual factors that make quitting difficult are also related to self-selected use of pharmaceutical aids when trying to quit. For instance, heavier smokers are more likely to use a cessation aid and also less likely to successfully quit. In social science and medicine this bias is known as ‘confounding.’”

Why did you study two “matched” patient groups?

“In our analysis, we attempted to address confounding variables using a method known as ‘matching.’ The goal of matching is to make study comparison groups similar with respect to potential confounders. In addition to cigarette consumption, we matched sociodemographics such as age, sex, race-ethnicity and education; smoking characteristics such as previous quit history and nicotine dependence; self-efficacy in quitting and having a smoke-free home.”

What did your study find?

“Even after matching, we found no evidence that the pharmaceutical aids improved the likelihood of successful quitting. While understandable, this finding is disappointing considering the need for successful cessation aids.

One possible explanation is that in many of the cessation randomized trials, smokers received the drugs in combination with intensive behavioral support. This support is not typically provided in the population. Prescribing behavioral support along with these drugs may be needed — as our results suggest that administering the drugs on their own is not working.”

What are you working on now?

“In collaboration with other professors at the School of Medicine and Stanford Business School, I am currently extending this work by studying how different groups of smokers respond to smoking cessation treatments, with the goal of developing tailored treatment plans.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Few California pharmacists prescribe birth control, a study finds

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It takes time and money to visit the doctor’s office to get birth control. This is particularly an issue for low-income women, those who live in rural areas and teenagers who feel uncomfortable seeing their family doctor.

So four states — California, Oregon, Colorado and New Mexico — are trying to make contraception cheaper and more readily available by allowing trained pharmacists to prescribe and dispense birth control pills, patches, injections and vaginal rings. However, pharmacists aren’t required to participate and few do, according to a new study.

University of California, Berkeley researchers investigated the availability and cost of pharmacist-prescribed contraception in California using a telephone audit survey of approximately 1000 community-based, retail pharmacies. Although randomly selected, most of the pharmacies were in urban areas and affiliated with retail chains, like CVS.

Posing as patients, they called the pharmacies and said, “I heard that you can get birth control from a pharmacy without a prescription from your doctor. Can I do that at your pharmacy?” If the answer was yes, then the researcher asked follow-up questions to identify the types of birth control available and the service fee.

The study found that pharmacy-prescribed birth control was available in only 11 percent of the surveyed pharmacies, with no availability differences between the rural or urban stores. They also determined that most participating pharmacies charged a service fee between $40 and $45.

“Our findings strongly suggest that more pharmacies need to offer this service to live up to the promise of widespread, easier access to birth control,” said lead author Anu Manchikanti Gómez, PhD, an assistant professor of social welfare at UC Berkeley, in a recent news release.

The authors noted that the current service fees may make birth control too expensive for some low-income women. They are hopeful this will improve once California’s Medicaid program starts reimbursing pharmacists for these services, which is required by July 2021.

They conclude the paper with a call for more research to identify the barriers to birth control accessibility.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Physicians urged to talk to their patients about guns

Physicians often discuss sensitive issues such as sexual behavior and substance use with their patients. Although everyone may squirm a bit, these conversations help doctors identify health risks so they can properly counsel their patients.

Now, there is a growing movement to add guns to the exam room discussion. Many professional organizations, including the American College of Physicians, recognize that gun-related injuries and deaths are a major public health problem, not just a criminal violence issue. So they advocate that physicians speak with their patients about firearms and intervene when patients are at risk for injuring themselves or others due to firearm access.

Editors from the Annals of Internal Medicine recently wrote, “Regardless of whether one believes guns hurt people or that people hurt people with guns, we have a public health crisis and health care professionals have an obligation to do what we can to combat it.” They later added in the editorial, “Physicians and other health professionals at the frontline of patient care can help prevent firearm-related harm one patient at a time.”

Although horrifying, mass shootings account for only 1 to 2 percent of deaths from firearm violence; other incidents involving guns cause about 95 such deaths per day. Such statistics inspired Garen Wintemute, MD, a professor of emergency medicine and director of the Violence Prevention Research Program at the University of California, Davis, to research firearm violence.

In a recent article in Annals of Medicine, Wintemute explained that people who commit firearm violence — whether against others or themselves — have well-recognized risk factors that often bring them into contact with physicians. These risk factors include alcohol and substance abuse, a history of violence, suicide attempt(s), poorly controlled severe mental illness and serious life stressors, he wrote.

However, not all physicians are comfortable discussing firearms with their patients, even if they think it is appropriate. For instance, they may feel they don’t know enough about firearms. Wintemute urges doctors to educate themselves and hospitals to develop continuing education programs on the benefits and risks associated with owning and using firearms. He also urges physicians to make a public commitment to ask their patients about firearms.

There are online resources to help physicians get the conversation started. For example, the Massachusetts Medical Society has online materials and a CME course that covers practical tips on how to talk to patients about gun safety. Wintemute is also happy to provide resources and to follow-up with physicians who make the online pledge — just click the box giving him permission to contact you.

An opinion piece in the Washington Post provides some additional guidance. In the article, Stanford resident Nathanial P Morris, MD, gave practical advise to physicians that identify a patient who owns a gun and wants to self-harm or harm others. “We can pursue a range of options, from handing out gun locks to requesting family or friends temporarily hold onto firearms to asking that local police perform a welfare check at the patient’s home,” he said in the piece. “In extreme cases, if patients pose an imminent risk to themselves or others because of mental illness, we can place them on a legal hold to evaluate them in the hospital for up to 72 hours.” The goal of these actions, he wrote, is to limit patients’ access to guns to protect them from transitory suicidal or homicidal impulses. Morris added:

“ We’re not out to get anyone’s guns. We don’t wake up hoping to infringe on patients’ personal lives. But, to keep patients and communities healthy, clinicians need to be able to ask about firearms.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

California bill aims for later school start times to protect teens’ health

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Odds are that you’re feeling tired when you read this. More than one in three American adults don’t get enough sleep on a regular basis, and studies show sleep deprivation is an even greater problem for teens. This poses a public health risk — inadequate sleep is linked to chronic diseases like hypertension, diabetes, depression, obesity and cancer.

“Society has not prioritized sleep,” Rafael Pelayo, MD, a clinical professor in psychiatry and behavioral sciences with the Stanford Center for Sleep Sciences and Medicine, told me. “Teenagers need more sleep than adults, so they are more vulnerable. Biologically teens tend to go to sleep later than when they were younger, but the schools start earlier. Teens should get close to 9 hours of sleep, but they get 7 hours or less.”

This epidemic of sleep deprivation among teens prompted California Senator Anthony Portantino (D-Glendale) to introduce Senate Bill 328, which would require middle and high schools to start no earlier than 8:30 am. Currently the average school start time in California is about 8 am, and some schools have a “zero period” that starts as early as 7 am.

“It is an extra 30 minutes or more every morning for the entire school year,” Pelayo said. “The later start time lets teens and families know that sleep is valued and respected by society. School districts that have changed their school start times have had demonstrable improvements in the health of the students.”

According to the American Psychological Association, studies have shown that starting the school day no earlier than 8:30 am increased attendance rates, grade point averages, state assessment scores, college admission test scores, student attention and student-family relations. They also found a decrease in disciplinary action, students sleeping during class and student-involved car accidents.

Such evidence inspired Pelayo to testify today in Sacramento in support of SB 328. He also rallied support among professional organizations and he plans to present letters of support from the American Academy of Sleep Medicine and the California Sleep Society, of which he is a board member.

Despite the evidence demonstrating the harm of sleep deprivation in teens, there are arguments against the bill. Opponents argue that school start times should be determined locally and that starting school later will be inconvenient. It is also viewed by some as a school policy issue rather than a health issue, Pelayo said.

Nonetheless, Pelayo believes the effort is important:

“Too many families end the day with an argument about bedtimes and homework and start the day with an argument about getting up in time for school. Twenty-five percent of teenagers self-report falling asleep in class and the actual number is likely higher. If a first or second grader fell asleep in class, the teachers would notify the parents since it is so unusual, yet for teens it is a daily occurrence. If this many teenagers were not getting enough food it would be a national crises, but since it is sleep it is ignored. Teens that wake up alert are healthier and do better both academically and in sports.”

The California bill comes at a time of heightened national awareness about teen sleep. Pelayo is speaking at the first national conference on school start times, which will be held in Washington DC later this month.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Clinical guidance on genetic testing: A Q&A

 

Photo by National Human Genome Research Institute

Earlier this month, an FDA ruling gave 23andMe permission to market its personal genetic tests for 10 diseases, including Parkinson’s and late-onset Alzheimer’s.

But with the increase in genetic testing at home and in clinical settings comes challenges. What do physicians do with all of these data? And how do they evaluate the validity and clinical utility of genetic tests?

To tackle these questions and others, the National Academy of Medicine formed a committee to provide guidance. I recently spoke with one of the committee members, Sean David, MD, DPhil, an associate professor of medicine at Stanford, about the committee’s new recommendations and report.

What inspired you to participate in the NAM Committee on the Evidence for Genetic Testing?

“The National Academy of Medicine consensus reports have high impact on national health policy and practices, so I jumped at the chance. In our work at Stanford, we struggle with advising patients on which genetic tests to recommend, which ones to order when requested by a patient and how to interpret results from the many direct-to-consumer genetic tests. We need guidance and a framework for making these decisions. The NAM committee addressed this challenge.

Years ago, I had a patient bring in a whole stack of direct-consumer whole genome sequencing results that showed her genetic risks for different illnesses. She asked me to interpret it for her, but there was far too much for me to consume during our brief office visit. And it was unclear what criteria to use when evaluating these tests. There’s been a rapid increase in the development of genetic tests with thousands of commercially available tests, but limited evidence regarding their validity for diagnosing disease and improving patient outcomes.”

What was the committee’s mission?

“Our charge was to examine the relevant medical and scientific literature to determine the evidence base for different types of genetic tests, as well as recommend a framework for decision-making regarding the use of genetic tests in clinical care.

This is the first consensus report on this topic. Although it was designed for the Military Health System, it should still be applicable to both military and civilian populations and may set benchmarks for private insurance companies. The report also encourages different agencies to cooperate and create a clinical data repository of evidence-based genetic testing decisions, which will be available to everyone. I think someone needs to do this to set the standard. Once that’s been done, at least we’ll have something we can all use as a benchmark.”

How can this decision-making framework help guide clinical practice?

“The decision framework can be used by physicians to determine which genetic tests are really ready for prime time in the clinic. For example, we know that if people are tested based on their family history and found to be at high risk for hereditary breast or ovarian cancer, they can have interventions that will improve their survival and outcomes. By using the decision framework, a physician can come up with a quick triage decision that it’s a ‘yes’ test for someone with several family members with breast and/or ovarian cancer, and one that really all providers should know about.

Other genetic tests like tests for Alzheimer’s aren’t as clear. For instance, there could be a genetic test for a particular rare form of early onset Alzheimer’s associated with a particular mutation. If someone has that mutation, he may have a very high risk of early onset Alzheimer’s disease. Do we screen people for that? It will depend on the clinical testing scenario. If someone has family members who developed Alzheimer’s in their 40s, then it might be a good diagnostic test. Whereas, there might be another genetic test for associated risk of dementia where the causal relationship with Alzheimer’s may not be established. That’s an issue of clinical validity. So we might not offer that test routinely — to avoid giving patients information that might be misleading and might even cause some harm.

In addition, ethical, legal and social implications of genetic testing are important. For many patients — including parents of children with undiagnosed rare diseases — genetic testing may help end a diagnostic odyssey. Oftentimes geneticists will order whole genome testing without testing for something specific. There may be thousands or even millions of different genetic markers that are tested with the hope that they’ll find something that leads to a diagnosis. Evidence of clinical utility may be lacking in scenarios like these, but taking into account the value of tests to patients and their families is important — the context matters. There needs to be a certain amount of clinical judgment, and the committee isn’t saying anything against this.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.