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Children's Hospital Boston Seeks Payor Partners to Contribute to Longitudinal Genomics Research


Originally published March 29.

By Turna Ray

A new program at Children's Hospital in Boston aims to not only integrate genomics into the routine care of young patients, but to demonstrate that this strategy can help lower healthcare costs.

At a time when budgets are tight, insurers are wary of paying for any interventions thought of as "investigational" — a label that payors have stuck on most marketed genetic tests for disease prognosis and drug response. As a result, a key goal of the new program, called the Gene Partnership, is to work closely with payors to prove the value of personalized medicine.

"If we are going to prove that we can save money" by incorporating genomics into the care of patients treated at Children's Hospital, "then payors should join us as thinking partners and share in those savings," Dietrich Stephan, executive director of the program, said last week at a conference focused on the reimbursement challenges surrounding personalized medicine.

Children's Hospital Boston, which is currently under significant pressure from Massachusetts officials to reduce costs, has championed the Gene Partnership as a way to rein in unnecessary spending in the long run by providing genomically guided personalized treatments, promoting disease mitigation strategies, and nurturing healthy lifestyles as children grow older.

Children also offer a fresh slate for conducting genomics research since environmental factors don’t yet have a heavy impact on their diseases and they aren't as settled into unhealthy lifestyle habits as adults might be. As such, the Gene Partnership aims to advance genomic medicine by sequencing children and using other patient data to validate new gene associations that can inform their care.

The project organizers are hoping to sequence 1,000 children in the next year. Ultimately, their goal is to sequence 100,000 kids in five years and follow them for their lifetimes.

The Gene Partnership plans to reach out to payors to cover the cost of sequencing for those children already getting single-gene testing. For now, Children's Hospital will subsidize the cost of exome sequencing for children enrolled in the program. As the program matures and gains more funding, and the cost of sequencing goes down, the initiative will move to whole-genome sequencing.

Insurers currently do not cover the cost of whole-genome sequencing, but there have been reports of people who have received life-saving treatments with the help of such testing and have applied to their insurers to make a case for reimbursement.

"I think the way we are going to get there with payors is if we all work together to show the outcomes improvements and cost savings on a case-by-case basis for personalized genomic medicine," Stephan said.

Patients who consent to participate in the Gene Partnership will be able to access their research data and communicate with researchers through a personally controlled health record, or PCHR. But they won't have access to all their genetic information.

The Gene Partnership's informed consent oversight board will decide which data should be returned to study participants. The ICOB, a concept borrowed from the Coriell Personalized Medicine Collaborative, uses a database of phenotype-genotype associations developed by Children's Hospital and Harvard Medical School, called SafeGenes, to decide which genetic information to report back to participants. Researchers then utilize a "research pager" technology to match de-identified data used in studies to actual patient records.

"The PCHR allows HIPAA-compliant messaging with the individual so that we may alert them to any health conditions that our scientific advisory board deems to be scientifically valid, and that our informed consent oversight board determines ethically and clinically appropriate to communicate," a Children's Hospital spokesperson told PGx Reporter. "The PCHR also allows the patient to contribute data back to our researchers to continue to expand our knowledge base."

Every child that walks through the door at Children's will be eligible to enroll in the Gene Partnership, which was officially launched in October. However, it will take time to gain consent from families and children, ensuring they understand the long-term commitment they are making and the risks and benefits of gaining knowledge through genome sequencing.

The informed consent procedures are "substantial" and explained by a genetic counselor to patients and their families, the hospital spokesperson added. Although researchers are hoping to gather longitudinal data on the children they enroll into the partnership, participants can choose to opt out of the study at any time.

The technology and infrastructure components that will facilitate the Gene Partnership, such as the i2b2 (Informatics for Integrating Biology and the Bedside) informatics framework and the PCHR platform Indivio, have been under development at Children's Hospital and partner institutions for many years with the support of various private and government research grants. The hospital estimates it has invested around $40 million into the program over the last decade. The initiative is trying to raise at least $50 million in the coming years to make it fully operational.

Reducing Costs

Gene Partnership organizers are soliciting the help of payors at a time when the Massachusetts state government is intensely focused on curtailing healthcare costs. According to reports, Children's Hospital has already lowered of the price of some of its services and made concessions to private insurers and Medicaid. The hospital is also attempting to reduce waste and unnecessary care by making institutional changes, such as improving the process of referrals.

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The Gene Partnership is hoping to demonstrate that genomic medicine can contain costs over the long term. So far, the promise that genomics strategies will help make healthcare more efficient and reduce wasteful spending has not panned out, because proving the cost-effectiveness of most genomically guided treatment strategies requires large, expensive studies that take years to complete.

These are exactly the types of studies the Gene Partnership is hoping to conduct. The impetus for the initiative emerged out of a desire to develop a sufficiently powered, annotated, and longitudinal population database that can facilitate the large-scale research projects needed to validate gene-disease associations in the context of patients' medical data, family history, and environmental factors.

Aiming to sequence 100,000 children and follow them over the course of their lives, the initiative's leaders make no secret of the fact that discoveries from the program will take time to materialize. "If we are going to make this viable over the long run, we need to prove its value and make it affordable," the Children's Hospital spokesperson told PGx Reporter.

Short of whole-genome sequencing, the hospital is already providing certain predictive genetic tests that promise to reduce healthcare spending for diseases that impact children, and insurers are starting to reimburse for them.

For example, Children's Hospital, in collaboration with the Autism Consortium, has been able to show in studies that chromosomal microarrays are better than fragile X testing or karyotyping in gauging gene abnormalities associated with autism. These findings, published in the April 2010 issue of Pediatrics, led the Autism Consortium to recommend that CMAs should be included among first-line diagnostics for children who display symptoms of autism but have no clear genetic cause.

Chris Walsh, chief of the genetics division at Children's Hospital, "has been successfully working with payors to have them adopt this as a reimbursable test," said the hospital spokesperson, adding that using CMA to test kids suspected of having ASD can yield long-term cost savings.

The lifetime cost of taking care of someone with autism spectrum disorder ─ which affects approximately one out of every 110 children in the US ─ is estimated to be around $3.2 million. Early identification, however, "results in early intervention with behavioral therapy, which has proven to be effective in improving the health status of children with autism and results in less testing, intervention, and support in the long run," the spokesperson said.

Armed with these examples and others, the Gene Partnership is putting together a working group that includes payor groups, Children's Hospital scientists and doctors, PricewaterhouseCoopers' personalized medicine practice, and members of the Personalized Medicine Coalition. The aim of the group is to pin down how all these different types of stakeholders can get value out of reimbursing for a patient's full genome sequence early in life.

Discussions between payors and Gene Partnership leaders are in the early stages and Children's hasn't yet disclosed any insurers who have agreed to pick up the tab.

Still, project organizers are trying to make a financial case for insurers to pay for the sequencing costs for those children who have a medical need to get tested for single-gene diseases, projecting that the "cost of an exome or a genome will be within range of the current reimbursement for single-gene sequencing in the next 12 to 18 months," said the hospital spokesperson. "We also hypothesize that full sequencing will provide valuable information that will improve treatments and save on the cost of healthcare."

Industry Incentives

Whole-genome sequencing data generated by the partnership could also fuel research that would have value for drug companies interested in developing new genomically targeted therapies and personalizing treatments in their pipeline with companion tests. The Gene Partnership is using the i2b2 informatics framework developed by Issac Kohane, head of the Children's Hospital Informatics Program, to mine the information in its patient database and generate leads about the interplay of genetics and disease.

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"Because we are able to query the database with very narrow inclusion and/or exclusion criteria, connect back to individuals in a HIPAA-compliant fashion, and offer them access to participate in trials, we believe we can dramatically accelerate the development timeline and reduce costs associated with bringing new tools to market through the clinical trials pipeline," said the hospital spokesperson via e-mail. "Recruitment is often the most difficult part of running a clinical trial or validating a diagnostic signature, and our 'on demand' genetically characterized cohort identification tools, we believe, will be very valuable to industry partners."

Research conducted by Stephan's team has already yielded leads about how genomic data delivered through the Gene Partnership infrastructure can impact treatment decisions. For example, genetic findings from a Phase II study suggest that a non-autism drug could potentially be repurposed as a treatment for ASD in children with a particular gene mutation. Details are sparse on this study since the data are unpublished. But the research "exemplified the multitude of sub-class-specific new companion diagnostic/drug combinations that are emerging from the research space and will need to be aggregated and delivered," Stephan said via e-mail.

Ultimately, the rate-limiting factor for the Gene Partnership's progress will be the engagement of its partners: the willingness of payors to contribute funds; the collaboration of drug and diagnostic firms; and the participation of families and children in the effort.

Then, of course, there is the cost of sequencing, which is dropping rapidly. For the time being, Children's hasn't settled on a sequencing platform, so it could not provide an estimate for sequencing costs.

"Initially, we believe the [sequencing] costs will be high but over time we believe we will bring those costs down and prove the value of every child having this information for a lifetime of informed health decision making," the spokesperson said. Whatever the sequencing costs are, however, Children's Hospital does not plan to pass it to children's families.

Have topics you'd like to see covered in Pharmacogenomics Reporter? Contact the editor at tray [at] genomeweb [.] com.

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