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The Importance of Registries in the Personalized Medicine Revolution: A Q&A With the President of CURE-1, Dane Dickson, MD
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The Importance of Registries in the Personalized Medicine Revolution: A Q&A With the President of CURE-1, Dane Dickson, MD

AJMC®: What is your view on personalized medicine, and what does the term encompass?

Dickson: Personalized medicine is an evolution of precision medicine. Personalized medicine cannot exist without precision medicine as the starting point. Precision medicine is the idea that we can accurately identify what makes patients or their disease distinct and how they interact with each other so that we can come up with a very specific treatment that will lead to a specific outcome in those patients. Personalized medicine, to me, is trying to reduce the amount of waste in treatments that do not have a chance of working or improving quality of life. We need to reduce waste, improve quality of life, and keep people out of the hospital. Personalized medicine’s goal is to improve healthcare at a lower cost than is currently being realized by avoidance of waste and avoidance of unnecessary treatments. 

AJMC®: How are registries important in gathering data to support personalized medicine?

Dickson: The field of precision diagnostics is the core of precision medicine. The problem we run into right now is that the core of precision medicine has rapidly expanded over the past 15 years, expanding much quicker than the evidence associated with the individual diagnostics. We have powerful tools, but we don’t know how to use them. Registries have 2 important functions. One, registries can require that the testing that is taking place has undergone some type of standardization. One of the problems that we run into in advanced diagnostics is that everyone does them a little differently, such as next-generation sequencing. Most people can identify the certain types of alterations no matter what they use, but there are more specific alterations that are very differently identified by different laboratories. Registries can provide a standardization of the testing so everyone is speaking the same language. Two, registries can keep track of outcomes associated with the testing-associated treatments so that we can show that it is beneficial and learn which individual patients with what individual diagnoses with what individual treatments can lead to specific outcomes. Registries standardize and collect outcomes data that we can then use to build upon a body of evidence that will allow us to build real personalized medicines. The registries are a key portion in the development/evolution of precision medicine to personalized medicines.

AJMC®: What is the role of CURE-1 specifically in advancing

personalized medicine?

Dickson: CURE-1 was built to act as a catalyst to bring the payers and the technology and the laboratories together in an area where technology can be introduced and payers could understand the quality of that testing and the benefits of the testing in such a way that the testing can continue to be improved upon. For example: We use next-generation sequencing because next-generation sequencing is such a key tool in precision medicine. We have established a registry that allows a payer to come in and cover the testing and say to the laboratory, “We’ll pay for the testing, but we need you to submit your data to this registry,” and for the clinicians using this test, “Please tell us how you used this test, what treatments you gave the patient, and how the patient responded.” By going through and standardizing the testing, which we do through medical oversight committees, we are basically asking, “Laboratory, are you doing a reasonable job of validating your tests? And here are the standards we are looking for.” Once the laboratory has met the requirements, we are working to get payers to require that they use the standardization and the registry to allow the testing to take place. The clinicians need to report to the registries so that we can learn how the testing is being used, how it’s useful, and how we can improve it.  

AJMC®: How do you manage the large amount of data generated through next-generation sequencing? Do you generally use the results in terms of specific biomarkers, or are you using results for individual patients who use the entire result? 

Dickson: All of the above. Every time we do next-generation sequencing, we do DNA prep steps. The DNA prep step is different in each lab because of the different libraries. We capture what type of laboratories were used and how they did it in their general forms. Then we capture what type of instruments they use and what kind of sequencing that they are doing (eg, whole exome, targeted genetic regions, comprehensive analysis). This is called metadata. We also collect the raw data file that comes off the instrument. We collect those, then we collect the files that come off the bioinformatics pipeline that interpret the raw data. Then we collect the file report in a standardized fashion. In this process, we are collecting granular genomic data that no one else in the world is doing. We are doing this because there are so many different steps that are required to run a next-generation sequencing test that it requires an understanding of what is happening in each step. We have hundreds of thousands of permutations on how you can do next-generation sequencing. Some people have different laboratory preps, some people have different bioinformatics pipeline tools, and there are other differences between laboratories. There are papers that show if you alter any of these aspects, you will get different results in certain specific queries. Our group is saying that we are going to collect each one of those data files. What do we do with each of those data files? The files are gigabytes in size—approximately 20 to 30 gigabytes in size. Whole exome sequences are even larger—approximately 1 terabyte in size. This information is put into storage because we recognize that those files are going to help once we start collecting outcomes. Then we can drill down into specific files and analyze what happened with each patient. For example, I get this patient and the laboratory says that they are EGFR [epidermal growth factor receptor] positive. We do this for their final report, which is kilobytes in size. The kilobyte-sized file says that they have an EGFR mutation. If the patient does not respond to anti-EGFR therapy, we can go back and analyze whether the problem was that the bioinformatics failed to pick up something that it should have picked up, or was the problem the biology of the tumor? The only way you know that is by going through each step backward to determine was it really there, and that is where you’ll need the raw data files. I genuinely believe that next-generation sequencing is much more sensitive than any other technologies, right to the final operations, so a question is that sensitivity translates to utility, and that is where registries come in. With registries, we identify how many patients do respond to certain types of treatments. We find ways to improve certain processes to get better clinical results. We can go back to patients’ data files. Rather than looking at all the data to find the truth, the problem is that you need good data points to look back at. For example: I want to look at EGFR-altered patients, and I want to look at files generated from next-generation sequencing. I want to look at the patient’s tree and look at their response rates. That’s where our registries are moving this granular genomic information into high-level clinical outcomes. Payers are interested because it helps determine whether the tests are leading to appropriate treatments and appropriate outcomes. Our job is to identify those benefits and make them better. We need these registries to do general research. When we started this nonprofit organization, we did not have good standards from lab to lab; we did not have good data that are shared (data are not collected or locked up in electronic health records). We need nonprofit groups that can come in and say we will collect data in a precompetitive space and allow everyone to have access. 

AJMC®: How are new methods of next-generation sequencing continuing to reduce the cost and change the value proposition for these diagnostics platforms?

Dickson:  We have to be careful to note that there is a human component in any part of this. We are looking at such complicated technology, data, and methods to examine genes that we need people to verify that what we are getting is what we think we are getting. At some point, we can reduce the cost of the sequencing to pennies on a dollar, but we still need people like bioinformatics experts, bioinformatics mathematicians, and molecular pathologists to see what the results mean. We are going to lower the overall sequencing costs, but unless we get better in informatics, we are going to still see a personnel cost that is not going to decrease under a certain level for quite some time. However, with that said, testing that is done with the best individuals in the nation is still lower than the $2000 to $3000 range. You compare that to a hospitalization of a patient or a drug that does not work. These tests are important in saving costs once you get treatments that do not work or toxicities that can be identified or stopped from those patients who do not benefit.

AJMC®: How are these tests such as next-generation sequencing enabling the selection of currently available agents more effectively for subgroups of patients? Are there any important findings that have come out that have changed practice or have changed considerations in anything that is already performed?

Copyright AJMC 2006-2018 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
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