OnDose™ Frequently Asked Questions
Who is a candidate for the OnDose test?
Any patient with colorectal cancer for whom continuous infusional 5-FU therapy is being considered is a candidate for OnDose.
How is the OnDose test performed?
OnDose is a simple blood test requiring a small amount of blood (peripheral venous draw). The blood sample is collected in a supplied K2-EDTA tube. Then, a chemical stabilizer is added to the sample with a prefilled syringe and transfer device. After gently mixing, the sample is centrifuged by the clinician to obtain a 1 mL plasma sample. The plasma sample is then sent on the same day in a prepaid overnight package to Myriad Genetic Laboratories for analysis (see full Sampling Instructions). Usually, within 7 days, results are returned through Myriads Results Now web-based system or via the mail to the physician's attention. The OnDose data can be used to help optimize the patient's dose for the next cycle of infusional 5-FU chemotherapy.
Is the OnDose test validated?
Yes, the test is validated and is performed in our CLIA-certified and CAP-accredited laboratory.
How do I order OnDose for my patients?
The OnDose test kit will have a Test Request Form and sample checklist for further details on sample handling and submission. A sample kit can be ordered by contacting your Myriad Account Executive or Myriad Customer Service at 1-800-469-7423, or on the web at www.myriadtests.com.
How much does OnDose cost?
The list price for OnDose is $300 per test.
Will insurance and medicare pay for testing?
Our Managed Care Executives are actively amending our current contracts to include OnDose™. OnDose has been added to approximately 180 contracts to date and approximately half of our current contracts will have OnDose automatically added at the time of launch.
Myriad is in active communication with Medicare Medical Directors in regards to coverage, coding, and reimbursement for OnDose. An Advanced Beneficiary Notice of Noncoverage (ABN) will be required at the launch of OnDose for all Medicare patients. The most current ABN can be downloaded below.
Advanced Beneficiary Notice
What are the options for patients without insurance coverage?
Myriad recognizes that early reimbursement may be uncertain as the test's value and payer acceptance is being developed in the marketplace. For a limited time, Myriad will be offering the OnDose™ Patient Protection Program (after the patient's deductible has been met). This program is designed to protect patients undergoing infusional 5-FU chemotherapy from unexpected financial liability due to limited insurance coverage during the introduction of OnDose. For qualified OnDose patients, out-of-pocket costs will be limited to 20% of the billed charges from Myriad after the patient's deductible has been met. This equates to a maximum of $60 per test for patients enrolled in the Patient Protection Program. Patients can enroll in the Patient Protection Program by calling the toll-free number located on the Myriad invoice. The Patient Protection Program is not available to patients covered under Medicare, Medicaid, or other government programs, or those who reside in Florida, Massachusetts, Texas, Minnesota, Rhode Island, or other states where such a program is prohibited.
OnDose is also included in the Myriad Financial Assistance Program (MFAP), which offers testing at no charge for uninsured patients receiving infusional 5-FU chemotherapy and meeting established financial criteria. The most current criteria for patient eligibility can be found at www.myriadtests.com.
As with all Myriad tests, patients can set up a 24-month payment plan for any out-of-pocket expenses. In the case of OnDose, a 24-month payment plan would enable a patient to pay just $12.50 per month per test. Patients can request payment plans by calling the toll-free number located on the Myriad invoice.
How is OnDose billed?
Myriad bills the patient's insurance companies for OnDose and the insurance companies will be billed separately for each OnDose test (eg, for a patient who has 8 tests, there will be 8 bills at $300 per test instead of 1 bill for $2400).
How do payers who have preauthorization requirements authorize testing service that have multiple dates of service? For instance, if a member is going to have the same test done 7 times within a specific time frame, does the test have to be authorized each time ( 7 different times), or can the 7 tests be authorized once up front?
For clients who have to obtain preauthorizations on their own (ie, IPAs, IDNs, and certain HMOs), we have developed a standardized document that contains all of the pertinent information to aid in requesting the preauthorization for OnDose™. Part of this request is for multiple dates of service within the authorized time frame. For plans that require preauthorization and Myriad is able to make the request, we will continue to do so (just like with our hereditary cancer products).
How quickly will I receive my OnDose test results?
The expected turnaround time for OnDose results is 7 days after sample receipt, provided the Test Request Form is included with the blood specimen and is filled out completely, including preferred billing option. (Insurance billing requires a patient signature and readable [enlarged] copy of both sides of insurance card[s]. If 2 cards are submitted, indicate which card is the primary.)
Focusing specifically on patients with colorectal cancer, what clinical evidence supports the value of pharmacokinetically (PK)-guided dosing of infusional 5-FU in this patient population?
Dr Erick Gamelin and his colleagues recently published an important study in the Journal of Clinical Oncology. The purpose of the study was to assess the value of a PK-guided infusional 5-FU dose adjustment in controlling toxicity and improving efficacy in patients with metastatic colorectal cancer.1
This group conducted a phase 3, multicenter study that compared body surface area (BSA)-based dosing of infusional 5-FU plus leucovorin with PK-guided dose adjustment. In this study, each arm consisted of 104 patients who were treated with 5-FU (1500 mg/m2/week 8-hour continuous infusion with 400 mg/m2 of leucovorin). One arm used conventional BSA-based dosing. In the other arm, patients were dosed according to BSA in the first cycle with subsequent doses adjusted to a target level of 20-24 mg•h/L, based on drug levels determined by HPLC-based monitoring in the previous cycle.1
In terms of clinical efficacy, patients who received infusional 5-FU with PK-guided dosing had an objective response rate (complete + partial response) of 33.7%, which was double the 17.3% response seen in patients dosed by BSA. This difference in overall response rate was statistically significant (P=0.004).1
In addition, although not statistically significant, there was a trend toward improvement in median overall survival after 1 year in patients who received PK-guided dosing. The median overall survival was 22 months for the PK-guided group compared with 16 months for the BSA-dosed group (P=0.08).1
With respect to safety profile, severe toxicity was significantly reduced in the PK-guided dosing arm compared with the BSA-based dosing arm, regardless of the time of treatment (P=0.003).1
In summary, this study clearly demonstrated that individual 5-FU dose adjustments based on PK-guided dosing resulted in an improved safety profile, improved objective response rates, and a trend toward higher survival rates. These results support the value of PK-guided management of infusional 5-FU in the treatment of patients with metastatic colorectal cancer.1
What impact might PK variability have on patient outcomes?
It has been well-established that 5-FU plasma levels correlate with the biological effects of the drug - both in terms of clinical efficacy and toxicity.2-4 Therefore, PK variations may have significant clinical consequences.
For example, patients with low clearance rates of 5-FU may have higher plasma drug concentrations that can, in turn, result in serious toxicities. Conversely, patients with higher clearance rates may have drug levels that are not sufficient to achieve a therapeutic effect. These patients would be at risk of treatment failure and disease progression.2
When it comes to infusional 5-FU dosing, a recent study by Dr Erick Gamelin and his colleagues demonstrated that up to 85% of patients were not being optimally dosed.1,5 These data underscore the importance of developing a more precise and rational method for dosing a drug that, in 2009, remains the foundation for colorectal cancer therapy.
If PK guided dose management is a more rational approach to administering 5-FU, why aren't more oncologists use it?
The simple answer is that, until now, there has been no fast and practical method for oncologists to measure 5-FU plasma levels and to use a PK-guided dosing strategy - as the methodology has not been readily available to them.
Over the past 20-30 years, several different methodologies have been developed in research laboratories to precisely measure 5-FU blood levels. These include cell-based assays, gas liquid chromatography (GLC), high-performance liquid chromatography (HPLC), and most recently, liquid chromatography-tandem mass spectrometry (LC-MS/MS).6-9
Using these research tools, several studies have demonstrated that a PK-based dose management approach for infusional 5-FU can improve clinical outcomes and reduce toxicities. These studies have also helped to establish dose adjustment guidelines designed to bring 5-FU plasma concentrations into optimal therapeutic ranges.1-5
References:
1. Gamelin E, Delva R, Jacob J, et al. Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(13):2099-2105.
2. de Jonge ME, Huitema ADR, Schellens JHM, et al. Individualized cancer chemotherapy: strategies and performance of prospective studies on therapeutic drug monitoring with dose adaptation. Clin Pharmacokinet. 2005;44(2):147-173. 3. Ploylearmsaeng SA, Fuhr U, Jetter A. How may anticancer chemotherapy with fluorouracil be individualised?
Clin Pharmacokinet. 2006;45:567-592. 4. Hon YY and Evans WE. Making TDM work to optimize cancer chemotherapy: a multidisciplinary team approach. Clin Chem. 1998;44:388-400.
5. Gamelin EC, Danquechin-Dorval EM, Dumesnil YF, et al. Relationship between 5-fluorouracil dose-intensity and therapeutic response in patients with advanced colorectal cancer receiving 5-FU containing infusional therapy. Cancer. 1996;77:441-451.
6. Smith CG, Grady JE, Kupiecki FP. Blood and urine levels of antitumor agents determined with cell culture methods. Cancer Res. 1965;25:241-245.
7. Cohen JL, Brennan PB. GLC assay for 5-fluorouracil in biological fluids. J Pharm Sci. 1973;62(4):572-575.
8. Christophidis N, Mihaly G, Vajda F, Louis W. Comparison of liquid- and gas-liquid chromatographic assays of 5-fluorouracil in plasma. Clin Chem. 1979;25(1):83-86.
9. Beumer JH, Courtney J, Stocker D, et al. 5-Fluorouracil measurement by liquid chromatography/tandem mass spectrometry and stability in human blood and plasma. Clin Colorectal Cancer. 2007;417-419.
Myriad Genetic Laboratories, Inc.
320 Wakara Way, Salt Lake City, UT 84108
1-800-469-7423 | E-mail: ondose@myriad.com
Myriad, the Myriad logo, OnDose, and the OnDose logo are either trademarks or registered trademarks of Myriad Genetics, Inc., in the United States and other jurisdictions.
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