Survey of the Characteristics of a Range of Tests

Publication Details

Howard McLeod, PharmD, Director of the University of North Carolina (UNC) Institute for Pharmacogenomics and Individualized Therapy, examined the current state of genetic testing.

Medicine is moving toward the vision that Francis Collins, Director of the National Human Genome Research Institute (NHGRI), presented in 2003 [note 3]. Collins envisioned that each of us will eventually have our genetic sequence stored within an accessible medical record, and that we will have highly individualized preventative medical care. When we are in need of treatment, our decisions regarding medication type and dosage will be tailored to the individual.

Molecular diagnostics is a field that is rapidly growing and changing and leading us closer to Collins’ vision. However, technology is evolving faster than the integration of genomics into medical practice.

The bottlenecks to progress are not all scientific. They include (1) the practices and habits of clinicians, (2) the costs associated with new tests, and (3) a lack of understanding about what these tests can and cannot do.


McLeod presented information about warfarin, a very commonly prescribed blood thinner, as an example of a drug that is ideally suited to pharmacogenomics. The intent of pharmacogenomics is to take genetic information and use it to determine appropriate medication, including a safe and accurate dose. It is difficult for clinicians to determine the correct dose of warfarin for various patients because people metabolize the drug differently. If you give a patient too much of the medication, serious side effects can occur. If you prescribe too little, then the drug fails to prevent blood clots. Doctors have traditionally arrived at a steady dose by tweaking a patient’s dosage based on observed responses to treatment.

Genetic testing can now be used to help determine proper dosage for individual patients. This type of testing greatly reduces the time to stable dosing. The FDA has approved updated labeling for warfarin that explains the importance of genetic data in prescribing the drug [note 4].

While tests like the one for warfarin certainly represent medical progress, it is important to keep the actual state of healthcare in mind. In a perfect world, physicians would always prescribe the correct dose from the start. Yet even with the genetic test for warfarin, this happens only 63% of the time. While this is a significant improvement over traditional prescribing methods (which yield a 9% initial success rate), there is still substantial room for refinement in the management of this drug.

Genetic Constitution

It is essential for physicians to remember that DNA is only one factor to be considered when determining correct dosage. Age and body size are also important. In fact, it is vital for both the scientific community and the public to remember that genetic make-up is only one aspect of an individual’s disease potential. There are many other contributing factors such as stress, exercise, and alcohol consumption.


McLeod described molecular testing as a field that focuses on “trouble.” The first goal is to preempt trouble. This is an attempt to anticipate what the patient will face in the future. It is the reasoning behind newborn screening programs and the rationale for predicting breast cancer recurrence. It enables families to deal with the emotional aspects of disease and plan ahead.

The second goal is to understand a patient’s current trouble. Treatments and strategies are developed to deal with symptoms. For example, tests are run to predict the likely origin of a tumor.

The third goal is to avoid trouble. Ideally, we will be able to use genetic markers to identify at-risk individuals and intervene prior to the development of disease. Overall, to deal with “trouble,” we must develop tests to assess (1) risk of disease, (2) risk of side effects from medication, and (3) risk of lack of benefit from a particular medication.

Established methods of approaching single gene disorders have provided the basic infrastructure for the newer, more complex diagnostic tests. While genetic tests have only focused on mutations in a single gene that correlate with disease, genomic tests consider multiple gene interactions, gene expression, and sometimes the individual’s genome. Many lessons have been learned and applied— for example, the value of genetic counseling is now well established.

According to McLeod, there are more formal evaluation frameworks for tests now than there were five years ago. The pathology community is serious about systematic reviews of testing. Nevertheless, “an unfortunate bit of craziness has occurred in the marketplace” with some direct-to-consumer (DTC) tests. McLeod suggested that additional industry-led certifications could provide the equivalent of a “Good Housekeeping Seal of Approval” and that this might be a better regulatory solution than additional legislation.

Patient Education

At this point in time, other members of the medical team—not the patient—still primarily make treatment decisions. However, McLeod contended that patients:

  • are very interested in their test results
  • are capable of developing an understanding of complex diseases and tests
  • desire details of their medical records
  • do not usually retain long-term memory of the details of their medical records
  • want to be part of the decision-making process

Government, academia, and practitioners need to better understand that information can be taken “all the way to the patient.”

In order to accomplish this information transfer, there is a great need for patient education tools. Patients need creative resources that are visually stimulating and accessible across the literacy stratum —for example, comic book formats are effective. Advocacy groups often provide the bridge between the medical community and their patients by creating literature that translates scientific information into a consumer-friendly format.

With Choice Comes Decision

There are now multiple therapeutic options for most diseases, but “with choice comes decision.” It can be difficult to choose the correct therapy – patients exhibit wide response variations, and drug toxicity can be unpredictable. The cost of tests and therapies remains an issue, and therapy rationing is a reality. Both the payers and the patients factor cost into treatment decisions.

McLeod noted that disease prevalence is not the only consideration for allocating resources. Ethical, legal, and social issues (ELSI) must be taken into account, and rare situations merit research, too. He cited the severe drug reaction known as Stevens-Johnson Syndrome. Though a rare event, the syndrome’s devastating effects make it a powerful example.