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Ancestry Grant Marks New Direction for Wolters Kluwer's UpToDate


CHICAGO – UpToDate has been producing clinical decision support content since 1992, but its new partnership with Ancestry represents a new direction for the pioneering company.

For the first time, the Waltham, Massachusetts-based unit of Dutch publishing conglomerate Wolters Kluwer soon will be able to frame the results of direct-to-consumer genomic tests in a clinical context to assist physicians in assessing and treating their patients.

Ancestry recently made a $1 million educational grant to UpToDate to develop a system to help physicians interpret and act on genetic test results. Ancestry CEO Margo Georgiadis announced the grant Oct. 29 during a keynote at the HLTH conference in Las Vegas.

It is an unrestricted grant because UpToDate wanted to maintain its editorial independence, according to Peter Bonis, CMO for clinical effectiveness in Wolters Kluwer's health division, so Ancestry will have no say over what kind of content the recipient will create.

"We don't take ads or drug company money or anything like that. Everything that we do is done as transparently as we can," Bonis said. "We have very strict policies around conflict of interest."

UpToDate, which develops evidence-based information for clinical decision support systems, will use the grant to create content to assist physicians in advising their patients. UpToDate and Ancestry expect to have the content available through both companies' portals starting in early 2020.

Ancestry will deliver test results through its recently launched AncestryHealth professional-grade testing service. Georgiadis said in October that the company is "committed to ensuring broad availability of educational materials to support healthcare providers who are engaging with patients about genetic risks and the proactive steps they can take to improve health outcomes."

That fits with the goals of UpToDate. "Our mission is to deliver evidence-based content that is constantly refreshed to practicing clinicians and trainees throughout the world," Bonis said.

As so much new literature is focused on genomics, it would be impossible to keep the content fresh without genetic and genomic knowledge, a relatively new area of focus for the long-established company.

UpToDate was founded 27 years ago by Burton "Bud" Rose, a nephrologist at Brigham and Women's Hospital in Boston who had written what was then an important textbook about fluid and electrolyte disorders, according to Bonis. That was not long after personal computers had become common in the business world.

"Bud thought that he should avail himself of that technology by creating that book in electronic form, but organized in a different way, which was to answer clinical questions," Bonis said. Rose rounded out the knowledge on fluid and electrolyte disorders by including other aspects of nephrology in this electronic textbook that he created in his basement with his wife, Gloria, and programmer Joe Rush.

The first version came on 14 floppy disks. UpToDate later expanded to many other medical specialties, including endocrinology, cardiology, rheumatology, pulmonology and critical care, gastroenterology, obstetrics and gynecology, psychiatry, anesthesiology, general surgery, and various areas of primary care. Wolters Kluwer bought the company in 2008.

"Genomics is the latest addition to our efforts," Bonis said.

UpToDate is available online in more than 180 countries, including some where Wolters Kluwer does not sell the product commercially, thanks to a partnership with a Harvard Medical School program called Better Evidence.

All of UpToDate's material is original, written by a collection of about 6,700 contributors, mostly practicing clinicians who have been published in medical journals and who must be invited to participate. "They actually are caring for the types of patients that they're treating," Bonis said.

That network now includes about 15 genetic counselors and nearly 100 clinical geneticists or directors of genetics clinics, Bonis said. "We also have a core set of approximately 25 UpToDate topics that discuss basic genetics concepts and their application to clinical care," he added.

Many other contributors have "deep, deep familiarity with the genetic components of the specific disorders they treat and the patients they care for," according to Bonis.

In addition to the contributors, UpToDate has more than 50 in-house physicians as deputy editors plus an editor-in-chief for each specialty, as well as a network of peer reviewers, all of whom are trained in evidence-based medicine and in writing, Bonis said. This team curates content to assure that it is accurate, evidence-based, useful, and actionable at the point of care.

The editors search and review hundreds of journals to keep UpToDate, well, up to date. They also respond to feedback from the 1.8 million users of the software.

Prior to the Ancestry deal, the Wolters Kluwer division was offering genomic information, though through a different lens.

"We have quite a bit of coverage on diseases that have a genetic underpinning. That might be that you have a patient with Lynch syndrome, and then we would describe the things that you'd expect that you need to know as a practicing clinician," Bonis said.

It has not been uniformly successful.

Sarah May, a general hematologist-oncologist at a Dana-Farber Community Cancer Care site in Weymouth, Massachusetts, has been using UpToDate since she first had access to computers in a practice setting in 2002. Dana-Farber Cancer Institute covers the cost of the service, which includes online access to some continuing medical education, May said.

May now turns to UpToDate about four to six times a day.

"I initially accessed it for general medical questions and management which I continue to do, but now access frequently for medication questions/toxicity, diagnosis, staging, and prognosis of all cancers," May said via email. She called it a "great supplement" to National Comprehensive Cancer Network guidelines for standard patient management and for understanding therapies. 

May said that she frequently sees patients with abnormal results from genetic tests performed at professional laboratories. She has not, however, used UpToDate or any other online resource to help her interpret genomic panels in the context of NCCN guidelines because "there appears to be little available on this matter," May said.

"I would be very interested in any collated information in table form as to how to manage various mutations of varying penetrance and risk. These are time-consuming visits with a great deal of anxiety on the part of patients."

Direct-to-consumer genetic tests could complicate that equation further by presenting a different set of challenges and questions than panels ordered by physicians.

"We believe that Ancestry and other companies that are beginning to scale up direct-to-consumer genetic testing are now going to create the potential risk for friction in the medical system" Bonis said. Patients are starting to bring results into their primary care doctors, who likely are not trained in interpreting genetic tests and may not have the time in a routine visit to address DTC tests.

"They get a piece of paper and a concerned patient. What is the next step?" Bonis said. "What are the implications of those tests and how do you properly counsel the patient?"

He said that UpToDate already covers many major genetic diseases, but the addition of DTC test results necessitates a new perspective.  

Genetic test results can be "fluid," Bonis said, as can what is known about certain markers. "There is a dynamic component to the knowledgebase around the implications of those gene tests," he said.

That is different than a patient coming in with a diagnosis or a known risk factor for a specific disease based on a physician-ordered gene panel.

"We had to reorient how we're thinking about delivering that content and understand the audience," Bonis said.

UpToDate wants to address this need for patients and medical professionals alike with trusted content written in a way that primary care physicians can understand and act upon. "We are now rolling up our sleeves to write this new type of content that is designed for that purpose," Bonis said.

All of the content, including the new DTC genetics content developed under the Ancestry grant, will become part of the main knowledgebase, available to all UpToDate users.

The process is laborious, with peer review. "There is a lot of back and forth to make sure that the material is as accurate and transparent as possible," Bonis said.

UpToDate has added machine learning in recent years to improve its search functions. "It's a self-learning system so that we can be very good and very precise at getting people information that they're going to want [when] using these advanced technologies," Bonis said.

The expectation is that the Ancestry partnership will outlast the grant. For certain, consumer-facing genetic testing is growing. "We want to make sure that we are responsible for providing the best information we can so that the best decisions can be made on behalf of all of us," Bonis said.