Imprecise research threatens precision medicine

The right treatment for the right patient at the right time. That’s the mantra of what is called precision medicine . To date, however, the inaccuracy might be a better medicine nickname.

precision medicine aims to be a transformative paradigm moving away from the “one size fits-all” approach in which treatments work for some people but not for others. For the average American, especially one who has cancer, medicine precision sets a high expectation of a more specific, and therefore more effective, treatment.

However, all too often, the science behind these targeted therapies has not been up to snuff and the result has been greater uncertainty about the optimal treatment -. Just the opposite of what the precision medicine intends to do

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As recently wrote in Science , three main obstacles are preventing the drive toward precision medicine truly transformational: researchers often not rigorously prove biological theories that supposedly explain why a specific treatment should work; They have not been fully determined the accuracy of diagnostic tests used to determine whether a patient is a good candidate for therapy; and there is little coordination among researchers, which has led to the inefficient investigation.

biological questions theory. In the past, researchers need not know precisely how a drug worked while improved health or lives saved. For example, statins class of drugs were originally thought to prevent heart attacks by reducing the amount of harmful LDL cholesterol in the bloodstream, but it can actually achieve its cardioprotective effect by inflammation cooling.

precision medicine is supposed to work differently. Basic research identifies a gene or protein believed at the root of a particular disease or condition. A drug is developed to modify or gene products block the action of the protein. a diagnostic test to determine who carries the gene or has an abnormal level of proteins, and so should receive the medication is created. All these steps are based on the assumptions of biological theories that, unfortunately, can be inaccurate or incomplete.

An example of this is cetuximab (Erbitux). Developed as a precision medicine against metastatic colorectal cancer, the FDA initially approved in 2004 cetuximab in patients whose tumors as positive for a protein called EGFR. However, the pivotal clinical trial that led to FDA approval any EGFR-negative patients not enrolled. That’s a problem because it made it impossible to test the key biological hypothesis that cetuximab would not benefit EGFR-negative patients. Researchers later discovered that the production of EGFR is basically irrelevant to whether patients with metastatic colorectal cancer will benefit from cetuximab. Instead, another genetic marker, a mutation of a gene called KRAS, better predicts that will benefit from the drug.

Because the biological connection between the abnormal gene or protein, cancer, and diagnostic tool was not tested carefully before approval of cetuximab, some patients who have benefited from the drug did not succeed while others did get the drug – and its harmful side effects – even though it had essentially no chance to benefit from it. This is exactly what is supposed to precision medicine to avoid.

the management of uncertainty. In conventional disease research, a group of individuals take a drug that is believed to treat a particular condition. The result is whether they will improve. Precision in medicine there are additional things to consider. What genes, proteins, or other biomarker is involved? What diagnostic test is used to identify it? What is the best medication for the treatment of individuals with biomarker? Uncertainty any of these questions clouding treatment decisions.

One of the most known biomarkers, HER2, is a receptor protein located on the cell surface of breast cancer. The more HER2, more “grow and divide” cancer cells signals are sent. Drugs such as trastuzumab (Herceptin) and lapatinib (Tykerb) HER2 head straight. The basic test measures the amount of HER2 protein on cell surfaces. A score of 0 to 1+ is typically classified as negative HER2 2+, is on the edge, and 3 + is HER2 positive. However, different laboratories and different pathologists use different rules to decide whether the test results are positive or negative. That means that some women who would benefit from taking anti-HER2 do not benefit from them, while others who are HER2 negative benefit from them. After a lot of study, still we do not know exactly the cut-off score for treatment with anti-HER2 drugs.

Wild west. When a variety of different research teams, laboratories and companies are working in the same area, it is often difficult to know whether the results generated are comparable, since no one is ultimately responsible for the results of dual control or coordination of the company.

An example of this involves a treatment for lung cancer. Many teams are looking for more precise targeting chemotherapy for lung cancer using a biomarker called excision repair cross-complementation group 1 protein (ERCC1). In theory, the chemotherapy drugs cisplatin and carboplatin work best for people whose tumors have less protein ERCC1. Actually, it is more complicated – and more daunting -. That

A evaluation of 33 studies ERCC1 and chemotherapy of lung cancer showed much heterogeneity in diagnostic methods and punctuation rules that the results are essentially unique. So after more than a decade of research, we still do not know whether measurement of ERCC1 makes the difference. However, numerous ERCC1 test kits are available commercially and are used to help chemotherapy “guide” of lung cancer.

way to go. The purpose of precision medicine is admirable. However, it will take longer to get there and cost much more than expected given the current inefficiencies research. Multiple research groups are exploring the same objectives with little communication and supervision. Rather than lead to better, more reliable biomarkers tests and treatments, these uncoordinated efforts can sow confusion and undermine interventions to improve the health of patients.

does not have to be. We must demand the same high quality evidence medicine precision as we do for any new medicine, including randomized trials that account for the presumed mechanism of action. In addition, a central, up to date database of public access to evidence regarding biomarkers and diagnostic tests – perhaps coordinated by major research institutions such as the Research Institute of the National Human Genome and the Institute national Cancer – help improve transparency and reduce waste and inefficiency in the pursuit of precision medicine.

Spencer Phillips Hey, PhD, is a research fellow in the program in the Regulations, therapeutic, and law (portal) at Brigham and Women’s Hospital and a faculty member at the Center Bioethics Harvard Medical School. Aaron S. Kesselheim, MD, is associate professor of medicine at Brigham and Women’s Hospital and professor at Harvard Medical School and director of the portal. The opinions expressed herein previously published in Science .

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