This story was originally published Nov. 8.
Molecular diagnostic labs in Germany have stopped next-generation sequencing-based testing for most patients after Germany's statutory health insurance system halted reimbursement for such tests at the beginning of October.
Following the exclusion of NGS-based tests, many labs have reverted to old technology, such as single-gene Sanger sequencing, which is still covered by insurance, using it to replace multi-gene diagnostic panels for hereditary disorders or NGS-based cancer gene mutation assays for certain tumor types. However, those older tests compromise patient care, they say, because they are inferior to the more sensitive NGS tests.
In the meantime, decision makers for insurance coverage have asked a working group to bring reimbursement for human genetics services up to the "state of the art of science and technology" by July 1, 2014. That group is widely expected to develop new codes for NGS tests.
Germany's mandatory health insurance system, called "statutory health insurance," covers about 90 percent of the country's population, or approximately 64 million individuals. The system originates from legislation passed in 1883 under Otto von Bismarck. Unlike the UK's National Health Service, it is a decentralized system — coverage is provided by about 130 health insurance organizations, called Krankenkassen or "sickness funds," at standardized levels. Health insurance is funded through income-dependent contributions from employers and employees, as well as government subsidies. Individuals above a certain income level, as well as federal employees and self-employed persons, can opt out of the mandatory system and obtain private health insurance, which is not affected by the recent changes in reimbursement for NGS tests.
A committee of stakeholders, including representatives of doctors, hospitals, and health insurance funds, called the Joint Federal Committee, or G-BA, determines which medical services are reimbursable under the statutory system. Another panel, the so-called Evaluation Committee, representing both doctors and health insurance organizations, maintains and updates the Unified Evaluation Standard, EBM, a catalog of codes for specific reimbursable medical services. Each service is assigned a point value, which can be translated into a reimbursement amount.
The EBM has never included a dedicated code for the reimbursement of next-generation sequencing-based tests. But until recently, molecular diagnostic labs used an existing code — position 11322, which covers sequencing-based tests designed to detect or exclude disease-relevant or disease-causing genomic mutations — to bill for such services.
That is no longer possible after the Evaluation Committee decided in June that starting Oct. 1, 2013, code 11322 applies exclusively to tests conducted by Sanger sequencing.
At the same time, the committee specified that codes 11320 and 11321, which cover tests based on probe hybridization and PCR, do not apply to microarrays, which had been ambiguous before.
In addition, the committee lowered the point value, or reimbursement, by 30 percent for all three codes, in addition to cuts to other human genetics services. For sequencing tests under 11322, for example, the point value is now 699 instead of 999, meaning the test can be reimbursed with up to €69.90 ($94), although actual reimbursement levels are often lower than that.
In a note accompanying the decision, the Evaluation Committee explained that it made its changes based on a cost study of medical services in human genetics, which showed a need to adapt the EBM, on the one hand, to the state of the art of science and technology in medicine, and, on the other hand, to offer services economically.
High-throughput methods, the committee said, did not exist when codes 11320, 11321, and 11322 were conceived, and were not supposed to be covered by them in the first place, which is reflected in the recent changes.
High-throughput methods, including NGS, can still be applied as part of so-called "indication-based molecular genetics step-wise diagnostics," but that includes only a limited number of hereditary diseases, such as cystic fibrosis and hereditary breast and ovarian cancer, and only up to a handful of genes for each disease.
Also, the cost study found that reimbursement levels for laboratory diagnostics, and in particular molecular genetics services, resulted in a "positive contribution margin," meaning a profit, and needed to be lowered. Reimbursement for counseling and test interpretation, on the other hand, was found to be too low to cover costs, and the committee added a new code for particularly time-consuming counseling.
The changes in the existing codes are the first step in an overall effort to overhaul reimbursement for human genetic services under EBM, the committee said. The second step will be "comprehensive further development of human genetic services under EBM," both through the addition of new human genetic services and through changes to existing codes to reflect the state of the art of science and technology.
To that end, the committee has tasked a working group to suggest further changes to EBM in the area of human genetics by July 1, 2014.
Patient care affected
The Germany Society of Human Genetics, a professional association that represents medical geneticists and scientists working in human genetics, is up in arms about the recent cuts in genetic diagnostics, and is lobbying for change.
In a newsletter posted on its website in early September, Klaus Zerres, the society's president, said that his organization, in collaboration with the Association of German Human Geneticists, is fighting for adequate payment for services provided by its members.
Zerres said he wrote to German Minister of Health Daniel Bahr to "point out again the disastrous effects of the planned cuts for our medical specialty."
A number of molecular diagnostic laboratories in Germany that started offering NGS-based tests over the last few years – both for the diagnosis of rare inherited diseases and for cancer diagnostics – have been affected by the new reimbursement rules for NGS.
Tübingen-based CeGaT, for example, offers more than 120 diagnostic gene panels for inherited disorders in at least 14 disease areas, at a price of €2,500 to €3,000 ($3,300 to $4,700) per panel. The company also launched a diagnostic exome test for inherited diseases, a somatic tumor panel with 552 genes, and a diagnostic tumor exome (CSN 8/14/2013).
While CeGaT's panels and exome tests were never covered by EBM codes, the company did obtain reimbursement from local sickness funds in its state for the validation of disease-associated mutations by Sanger sequencing, after conducting a panel-based screen, and for resequencing areas by Sanger that were not covered well by the panels. "That was significantly more efficient than sequencing all the genes by Sanger," Saskia Biskup, the company's CEO, told Clinical Sequencing News.
However, billing for confirmatory Sanger sequencing after an NGS panel is no longer permitted under the new rules. "Patients are now offered an inferior method – they receive stepwise diagnostics again," she said, which includes fewer genes and has a lower diagnostic yield.
According to Biskup, the decision to narrow reimbursement to Sanger-based tests was driven and supported by a group of human geneticists who have not yet been able to establish NGS-based diagnostics in their own laboratories.
The recent changes are "a step back, because [the Evaluation Committee] did not go in the direction they should have gone, which is to introduce EBM codes for next-gen sequencing," she said.
"Sanger-based testing is inferior for patients, it is more expensive, and it puts Germany in a poor position" relative to other countries, she said. "Overall, it is a catastrophe."
Her hope is that the new working group will develop NGS-specific EBM codes, including for gene panels, exomes, and whole-genome sequencing.
In the meantime, CeGaT is trying to obtain reimbursement for its NGS tests elsewhere. The tests are covered by some private health insurance companies, for example, and CeGaT plans to negotiate with individual sickness funds for coverage of patients on a case-by-case basis, outside of the EBM system.
In addition, the company is expanding its services abroad, hiring several staffers to promote its tests in the US, for example. Biskup said CeGaT is trying to "become more established internationally and become more independent of [the German] system."
The Center for Human Genetics and Laboratory Diagnostics, based in Martinsried just outside Munich, is another lab that has been compelled to replace NGS-based tests with Sanger sequencing.
The lab has been employing Roche's 454 platform in several oncology molecular pathology tests, including for colorectal cancer, non-small cell lung cancer, and leukemia (CSN 6/6/2012).
"Because of the new regulations, these tests now have to be switched back to Sanger sequencing for all patients who are not privately insured," Hanns-Georg Klein, the center's CEO, told CSN.
"For applications in molecular pathology, the new regulations do not save any money, instead they deprive patients with cancer from getting appropriate diagnostics of early mutational events – minorities − that cannot be adequately detected by Sanger sequencing," he said, adding that detecting such early events is crucial for monitoring the success of cancer therapies.
The center also recently introduced multi-gene panels for certain inherited disorders, as well as clinical exome sequencing for intellectual disability in children, tests that are also affected by the new regulations.
While Germany appears to be taking a step back from NGS-based testing, some of its neighbors are forging ahead with it. The Radboud University Medical Centre in the Netherlands, for example, is expanding its diagnostic exome sequencing program. As of this summer, the Dutch health insurance system reimbursed diagnostic exomes at €700 ($940), the same rate as other molecular diagnostic tests (CSN 8/21/2013).