College of American Pathologists
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June 2011

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Diagnostic tests in drug labels—AMP issues position statement

The Association for Molecular Pathology released its position statement May 16 on the appropriate manner in which to reference diagnostic tests in drug labels. The AMP met with Food and Drug Administration officials who help draft guidance documents for co-developed products and companion diagnostics to inform them of its new position statement.

Pharmaceutical manufacturers control the label’s content and can choose to describe a laboratory test by its molecular description or its brand name. The latter limits pathologists from choosing the test that best suits the needs of patients on targeted therapies as well as those of the patients’ physicians and the laboratory environment. Oncologists and other treating physicians may reflexively order the test listed in the labeling, rather than consult with the molecular pathologist to consider pertinent patient history and the best lab testing strategy at the least cost. Referencing diagnostic tests by their brand names in drug labeling may therefore create a situation in which patients do not receive optimal care.

“When the FDA approves a label that includes a brand name of a diagnostic kit, the medical community often views this as a tacit endorsement of that one company’s test,” explained AMP Professional Relations Committee chair Elaine Lyon, PhD, in a statement. “Indeed, diagnostic companies’ marketing strategies might exploit this view.”

Because health care providers may request testing using the test identified in the drug labeling, and payers may reimburse only if that specific test is used, laboratories will be put in the position of having to purchase and verify multiple test kits for the same analyte. In addition, if a diagnostic company was to sell its test exclusively to one laboratory, all specimens would have to be shipped to that laboratory for testing even if the source laboratory has access to a different FDA-approved or -cleared test for the same analyte. “This would drastically increase health care costs and over-complicate the laboratory environment. And our greatest concern,” Dr. Lyon said, “is that it could result in restricting the patient’s access to one specific test, which may create additional burdens to the patient, including the collection of subsequent samples, increased out-of-pocket costs, and delayed treatment.”

In its statement, the AMP recommends that the FDA specify that diagnostics be described by the biological description of the gene or mutation in drug labeling and that recommended diagnostic testing not be identified by brand name. Essential performance characteristics (for example, limit of detection) can be specified. Standardized HUGO nomenclature should be used.

The AMP says that identifying diagnostic tests by brand name in drug labeling is appropriate only in the description of relevant clinical studies; in the remainder of the label, the position statement says, pharmaceutical manufacturers should reference the biological description.

DNA of 50 breast cancer patients decoded

Washington University scientists have sequenced the whole genomes of tumors from 50 breast cancer patients and compared them with the matched DNA of the same patients’ healthy cells. This comparison allowed researchers to find mutations that occurred only in the cancer cells.

The work was presented April 2 at the American Association for Cancer Research 102nd Annual Meeting.

In all, the tumors had more than 1,700 mutations, most of which were unique to the individual, says Matthew J. Ellis, MD, PhD, professor of medicine at Washington University School of Medicine in St. Louis and a lead investigator on the project.

Washington University oncologists and pathologists at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine collaborated with the university’s Genome Institute to sequence more than 10 trillion chemical bases of DNA—repeating the sequencing of each patient’s tumor and healthy DNA about 30 times to ensure accurate data.

The DNA samples came from patients enrolled in a clinical trial Dr. Ellis is leading for the American College of Surgeons Oncology Group. All patients in the trial had estrogen-receptor-positive breast cancer. Patients received estrogen-lowering drugs before surgery. Twenty-four of the 50 tumor samples came from patients whose tumors were resistant to this treatment, and 26 came from patients whose tumors responded.

Confirming previous work, Dr. Ellis and his colleagues found that two mutations were relatively common in many of the patients’ cancers: PIK3CA, which is present in about 40 percent of breast cancers that express receptors for estrogen, and TP53, present in about 20 percent. Dr. Ellis and colleagues found a third, MAP3K1, that controls programmed cell death and is disabled in about 10 percent of ER-positive breast cancers. The mutated gene allows cells that should die to continue living. Only two other genes, ATR and MYST3, harbored mutations that recurred at a similar frequency as MAP3K1 and were statistically significant.

“To get through this experiment and find only three additional gene mutations at the 10 percent recurrence level was a bit of a shock,” Dr. Ellis says.

In addition, they found 21 genes that were also significantly mutated, but at much lower rates—never appearing in more than two or three patients. Despite the relative rarity of these mutations, Dr. Ellis stresses their importance.

“Breast cancer is so common that mutations that recur at a five percent frequency level still involve many thousands of women,” he says.

Dr. Ellis looks to future work to help make sense of breast cancer’s complexity. But highly detailed genome maps are an important first step.

“At least we’re reaching the limits of the complexity of the problem,” he says. “It’s not like looking into a telescope and wondering how far the universe goes. Ultimately, the universe of breast cancer is restricted by the size of the human genome.”

Nestlé to buy Prometheus

Nestlé has agreed to purchase Prometheus Laboratories, which specializes in gastrointestinal and cancer diagnostics, for an undisclosed sum as the Swiss food giant moves further into health care.

The acquisition will give Nestlé a springboard “to accelerate its current and future health care business,” Luis Cantarell, head of the company’s health science unit, said in a statement.

Health science businesses have been in a number of Nestlé’s recent deals as it tries to increase its presence in the fast-growing market for clinical nutrition. In August, it acquired Vitaflow, which develops treatments for inherited metabolic diseases, and in February it bought CM&D Pharma, also focused on inflammatory bowel diseases and cancer.

Nestlé said the Prometheus deal was part of an effort to develop “personalized nutrition strategies that will help in the management and prevention of chronic health conditions.”

Prometheus has about 500 employees and the unit is expected to generate $250 million in revenue next year. Pending regulatory and shareholder approval, the deal is expected to close in the third quarter. Jean-Philippe Bertschy, an analyst at Bank Vontobel, a Swiss private bank in Zurich, estimated the price tag at more than 1 billion Swiss francs, or more than $1.1 billion.