OnDose® FAQs
Sample Procurement
1. When do I collect the OnDose® sample?
Our internal research shows that the most reliable sampling time is at least 18 hours into the infusion. While most patients reach steady-state within two hours, a subset of patients takes longer to settle into steady state. Studies have shown that by 18 hours, patients are at steady state.
These conservative time windows ensure that samples are collected when patients are at steady state for 5-FU. These recommendations are for patients on FOLFOX 6 or FOLFIRI regimens. For patients on FOLFOX 4 regimens - which is a split infusion of 2 days X 22 hours - receiving their infusion by battery pumps, should be drawn between the 18th and 19th hour of infusion. Patients receiving FOLFOX 4 by non-battery pumps cannot use the OnDose test.
2. What is the difference between a battery operated pump and a non battery operated pump?
Internal studies of pump dynamics have revealed differences in flow rate based on the type of pump used during the patient’s continuous infusion of 5-FU. These data indicate that optimal results are obtained when blood samples are drawn within time periods specific to the type of pump used.
For battery pumps, such as Gemstar, Walkmed, etc., infusion rates can vary up to 6% from the planned infusion. This means that for a 46 hour planned infusion, the actual infusion may last from 43.2 – 48.8 hours. For battery operated pumps, OnDose samples should be drawn between 18 hours of the 5-FU infusion start, and at least 3 hours before it completes.
Non-battery operated pumps such as gravity, balloon and Baxter have greater variations with different pump types, especially at the end of infusion. The variations become particularly high during the last 10 hours of the infusion. For non-battery pumps, OnDose samples should be drawn 18 hours after the start of infusion up to 10 hours before the end of the infusion.
3. My patient arrived late, and it is 43 hours and 30 minutes into the 46 hour battery-operated infusion. Can I still take the sample?
No, but the patient can be tested at the next cycle. We ask that you only send in samples that were drawn strictly within the 18-43 hour time window, as required per OnDose parameters.
We have concerns if there is a blood draw outside of the stated time-frame, there can be a problems with the sample, and the AUC may not be accurate. Therefore, a patient could get an incorrect dose change in the next cycle, which could lead to either toxicity due to a higher dose than needed, or a less efficacious dose because of a lower dose recommendation.
4. What if the pump is beeping when I go to draw my patient?
You should determine if it is still appropriate to take the sample at this time. Ambulatory infusion pumps usually beep according to pre-set parameters, such as:
- Up-line/down-line occlusion
- Low battery power
- Infusion nearing end (pre-notification)
- KVO/TKO rate
- Infusion end
Please be aware when pump is beeping, it is an indication of an event that could possibly affect the OnDose outcome. The safest measure is to resolve the pump issue first, and then determine if the OnDose testing is appropriate at that time, using your clinical judgment.
5. What if I don’t collect the required amount of blood? Do I still place all the inhibitor into the collection tube? Will this dilute my sample?
The OnDose laboratory recommends the complete contents of the OnDose Inhibitor syringe be placed into the provided 6ml EDTA tube immediately after procuring the venous sample. The OnDose Laboratory has tested total blood volume sampling with as little as 3ml of whole blood, per 6ml EDTA tube for dilutional effect or outcome variation. The OnDose laboratory has noted no reportable change in AUC regarding these volume differences, as long as the blood sample is not less than 3ml.
6. Why does the OnDose sample need to be drawn from a peripheral vein rather than the port?
The OnDose test measures the 5-FU levels in the patient’s circulating blood. If you draw from the port, there will be excess 5-FU in the sample and the lab will report an inaccurate high measure. Flushing the port before taking the sample WILL NOT give an accurate reading.
Sample Processing
1. Why must I use the OnDose stabilizer for my lab samples?
It is critical that OnDose samples be injected with provided stabilizer syringe immediately after sample draw to prevent 5-FU degradation. Adding the stabilizer to the sample immediately after the blood draw inhibits the degradation of the 5-FU by specific enzymes present in blood cells, allowing for a more precise steady-state measurement of 5-FU exposure.
2. How does the stabilizer work?
The OnDose stabilizer is a derivative of uracil, with properties that irreversibly inhibits DPD (or dihydroprymidine dehydrogenase), which is an enzyme which causes the breakdown of 5-FU. By adding the OnDose stabilizer into the blood sample immediately, the DPD enzyme is inhibited and degradation of 5-FU in the plasma is terminated. Therefore, this process allows the sample to maintain 5-FU concentration levels that are stable for processing and shipment at room temperature.
3. Is it OK if the sample is hemolyzed?
Hemolysis is defined as the rupture or breakage of the red blood cell membrane, causing the release of hemoglobin and other internal cellular components into the surrounding fluid. Hemolysis causes a serum or plasma sample to take on a pink or red tinge.
We cannot accept a hemolyzed sample. There is a risk that DPD will be released from ruptured blood cells. Remember, DPD degrades 5-FU. Please try to re-draw the patient if the sample is hemolyzed, and if the patient is available within the 18-43h time frame.
4. Why must I send the sample as plasma instead of whole blood?
OnDose samples must be tested from plasma because there is evidence to suggest that the white blood cells (WBCs) (found in the buffy-coat of centrifuged specimen) begin to release uracil over time, which will falsely elevate the results of the OnDose test due to uracil cross-reacting with the antibody testing. Therefore, centrifuging the sample and separating the plasma from the cells is essential for OnDose testing even when the stabilizer is present.
5. What is steady state and why is it important with the OnDose sample procurement?
When the patient is at steady-state, the amount of chemo going into the patient is equal to the amount of chemo being broken down by the patient’s metabolism. The patient will be at steady state for much of the time during their infusion. Once the pump stops, however, the 5-FU will rapidly start to break down.
It is very important for accuracy that the blood sample is drawn while the patient is at steady state for the 5-FU infusion. The half-life of 5-FU is 13 +/- 7 minutes. Any interruption in infusion may have an immediate impact on the patient’s plasma 5-FU level. The patient must be receiving 5-FU during the blood draw, to get the correct measurement.
6. How can I ensure my patient’s OnDose sample is at steady-state?
To answer this question, let’s consider the following situations which may interfere with steady-state:
- Has the patient had chocolate in the past 12 hours? Chocolate consumption within 12 hours of the assay may falsely elevate the patient’s result.
- Has it been less than 18 hours since the start of the infusion pump?
- Has the infusion pump stopped?
- Has the infusion pump beeped within the last hour?
Please remember, the OnDose test is contraindicated in patients on theophylline.
7. How is drawing an OnDose sample similar to a peak and trough level?
A trough is taken before the start of medication; however, the peak is drawn at the optimal point of maximum absorption. The OnDose AUC is a little different than a peak level in that the Area Under the Curve: is like a plateau over time; not a single point in time like a Gentamicin Peak.
Area under curve is calculated as peak x exposure, which is 5-FU optimal concentration x total hours infused. Remember, you would not take a peak level if the patient’s IV was obstructed, the pump had problems, the patient had prohibited food that might change the level, or if the medication was not at its optimal level.
Remember the following:
- A peak level is one point in time, whereas an AUC is a window of time at steady state.
- Consider the same IV precautions as taken for a peak level measurement.
- The patient’s next dose is dependent on the integrity of THIS dose.
8. What are the most common sampling errors?
- A Non-Steady State Sample. For example the pump is at the infusion end.
- The Pump is kinked or the flow is obstructed. The patient may not realize this, however.
- Sampling the patient when the pump beeping. A beeping pump usually indicates problems.
- Sampling after infusion ends.
- Name on TRF does not exactly match sample tube.
- Hemolysis. White blood cell contamination will break down 5-FU. If this happens, the patient must be redrawn. Myriad will not accept hemolyzed samples.
Sample Shipping:
1. What should I do if I am unable to send the sample overnight or the next day? How long is my OnDose sample stable?
Myriad Genetic Laboratories needs to receive your sample within 7 days from the draw date. Samples not sent immediately can be stored at room temperature, in the refrigerator, or in the freezer.
2. Has the OnDose test been approved by FedEx for pickup and delivery?
The OnDose Sampling Instructions detail the correct procedure to send the sample to Myriad for analysis. When all shipping instructions are followed correctly, the current package meets the minimum packaging requirements and is acceptable for transporting the OnDose sample. The FedEx Clinical Pak contains an affixed lavender dot acknowledging the OnDose sample shipment has been approved by FedEx. For further questions regarding FedEx approval please contact Art Moes, Purchasing Manager, amoes@myriad.com or 801-584-3605 for FedEx Package Test/Evaluation Report # 26517
3. What are the most common OnDose test shipping errors?
- The plasma Cryovial Tube is not placed in the 50 ml red top tube.
- No absorbent tissue in the 50ml red-topped tube.
- No biohazard bag placed in FedEx shipping packet.
- The Test Request form has been placed inadvertently inside the biohazard bag, thereby contaminating the Test Request Form.
Test Request Form
1. What are the most common Test Request Form errors?
Each OnDose plasma sample must be accompanied with an associated Test Request Form. The OnDose Test Request Form has been designed to capture all information needed for the accurate and timely reporting of your OnDose sample.
The following items are the most common test request form errors:
- The specimen collection date is missing.
- The Provider Signature is missing.
- The Total 5FU continuous infusion dose is not in MG/M2.
- The Total hours of 5-FU continuous infusion is missing or is inaccurate.
- The hours from the start of infusion that the sample was drawn is missing or inaccurate.
- The Patient signature is missing, along with the appropriate insurance paper work. For example, signed Medicare Advance Beneficiary Notice of Non-coverage.
2. What is a 5FU mg/m2 dose?
- The 5FU Continuous infusion dose can be written in two forms:
- The mg dose
- Or the mg/m2 dose
- The mg/m2 dose is USUALLY NOT the dose on the chemo bag
- However, the mg/m2 dose IS found with the original physician order, which is usually in the patient’s chart
- The mg/m2 dose IS THE ORIGINAL DOSE before you multiply the BSA to get the mg dose.
General Questions
1. Can I use the OnDose test on patients who have other cancers besides colorectal cancer where they are on an infusional 5-FU regimen?
The Target AUC rang of 20-30 is used to get patients into this range, based on studies of patients with colorectal cancer. There are some studies in patients with head and neck cancer showing that patients with higher blood infusional 5-FU levels have better survival, but there is no specific target AUC range for patients with head and neck cancer. Patients on continuous 5-FU infusions for other diagnoses may be candidates, based on the Heath Care Provider’s clinical experience and judgment.
For further information, please contact Myriad’s Medical Services Department at OnDose@myriad.com or 800-469-7423 ext. 3701
2. Why is the OnDose test only used for infusional 5-FU and not Xeloda® or (capecitabine)?
Capecitabine is an oral prodrug of 5-FU. It is activated to 5-FU by multiple enzymatic steps within the cell. These enzymes are enriched in liver and the tumor. Therefore, the concentration of 5-FU in blood and tissue may be different. OnDose cannot be used for patients on capecitabine until studies are done to determine which AUC target range would be appropriate for these patients. These target ranges may be different than the AUCs for infusional 5-FU.
3. Can I use the OnDose test in patients receiving infusional 5-FU with concurrent Radiation Therapy?
An AUC for 5-FU + radiation therapy has not been established. This will require clinical trials. The target AUC of 20-30- mg.hr/L was established for 5-FU alone, and cannot be extrapolated to 5-FU used as a radiosensetizer, as it is commonly applied in rectal cancer.
In this type of treatment, a much lower dose of 5-FU is used (**-200mg/m2/day) vs. a FOLFOX Regimen of (**-2400mg/m2). Patients receiving radiation Therapy are especially sensitive to 5-FU, so these patient may experience much more toxicity at similar AUC levels. As we have not determined what the therapeutic AUC range is for patients receiving 5 –FU chemotherapy ,while also receiving radiation therapy, OnDose is not appropriate for these patients at this time.
For further information, please contact Myriad’s Medical Services Department at OnDose@myriad.com or 800-469-7423 ext. 3701
4. Which foods or drugs interfere with the OnDose assay?
Myriad Genetic Laboratories, Inc. has tested a variety of substances to determine if there is any interference with the OnDose assay. There are 2 interactions that can affect the accuracy of OnDose results:
- Chocolate contains theobromine, which is known to interfere with the OnDose? assay, causing a result that is too high. We require that patients not ingest chocolate within the 12 hours before their OnDose test.
- Theophylline interferes with the OnDose? assay and can produce a result that is falsely high.
5. How can you integrate the OnDose testing process into your current practice?
Nursing behaviors are crucial to OnDose sample success. The Nursing and lab coordination are imperative to positive outcomes for OnDose sampling.
To ensure sample integrity, please remember the key points for OnDose sample collection.
- The patient must be at steady state when the sample is taken. There should not be any interruptions to 5-FU infusion before the sample is taken.
- The sample must be drawn from a peripheral vein.
- Please label the tube with two patient identifiers.
- The stabilizer should be added immediately after the blood draw, and
- Hemolyzed samples will not be accepted. Please redraw the patient if gross hemolysis is noted after centrifugation.
For further information, please contact Myriad’s Medical Services Department at OnDose@myriad.com or 800-469-7423 ext. 3701
Billing Questions
1. How is OnDose billed?
The list price for OnDose is $300 per test. Myriad will bill the patient's insurance carrier for OnDose. Testing will begin upon receipt of the sample. A completed Test Request Form (with patient signature), and enlarged photocopy of the front and back of the patient's health and will appeal and resubmit claims if necessary.
Myriad bills the patients’ insurance companies separately for each OnDose test. It is recommended that OnDose is used each treatment cycle to achieve the optimized dose of 5FU. If there are any questions about the procedures or the charges on the bill, the patient should contact Myriad’s Billing Department at 1-800-725-2722 and not their physician’s office. Myriad has a variety of payment options to assist patients with the cost of OnDose.
2. How do payers who have preauthorization requirements authorize OnDose testing?
For physicians working with IPAs, IDNs, and certain HMO insurance plans, Myriad has developed a standardized document that contains all of the pertinent information to aid in requesting the preauthorization for OnDose. You can download the preauthorization form on this site. Part of this request is for multiple dates of service within the authorized time frame.
For plans that require preauthorization, and where Myriad is able to make the request, we will continue to do so just like we do with our hereditary cancer products.
3. My patient received an Explanation of Benefits (EOB) from the insurance company stating that the claim was denied. What should I instruct the patient to do?
The EOB is not a bill, but it may show pending payments or even a claim denial by the insurance company. When the insurance company processes a claim, the policy holder is sent an EOB notice. Sometimes the insurance company denies a claim because they want more information such as medical records, which may be information only the healthcare provider's office can provide. Once additional requested information is obtained, Myriad will send it directly to the insurance company, and the patient often does not need to take any action. If there are any questions about the procedures or the charges on the EOB, the patient should contact Myriad’s Billing Department at 1-800-725-2722 and not their physician’s office.
4. Does Myriad offer a payment plan?
Yes, Myriad offers a 25-month interest-free payment plan that can be set up by calling the Myriad Billing Department at 1-800-725-2722, which is also listed on the first Myriad billing statement. A due date and payment amount must be agreed upon to set up a payment plan. If the agreed-upon payment amount is not received by the due date, the payment plan may be cancelled and the patient may receive a past due statement. If this happens, please have your patient contact the Myriad Billing Department immediately to re-instate the payment plan and avoid further collection attempts.
In the case of OnDose, a 25-month payment plan would enable a patient to pay just $12 per test. Again, patients can request payment plans by calling 1-800-725-2722.
5. 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 hundreds of contracts to date.
Medicare has not established a coverage policy for OnDose testing. For Medicare patients, an Advance Beneficiary Notice of Non-coverage (ABN) is required before testing can begin. Because Medicare will not cover test costs until a reimbursement policy has been established, test costs will be billed to the patient. A summary of instructions and documentation requirements for Medicare patients is included on page 1 of the ABN.
You can download the ABN (including Medicare information) here.
Medicare patients can set up a 25-month payment plan for any out-of-pocket expenses. A payment plan would enable a patient to pay just $12 per test over 25 months. Patients can request payment plans by calling the Myriad Billing Department at 1-800-725-2722.
6. What if my insurance does not pay for OnDose?
For a limited time, Myriad will be offering the OnDose Patient Protection Program. 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 patients, the cost of OnDose will be limited to 20% of the fully billed charge of $300 from Myriad. 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 Myriad’s billing department at 1-800-725-2722 after receiving their first billing statement. It is important to note: any correspondence patients receive from their insurance company, such as an Explanation of Benefits, will probably not reflect a correct patient balance. Patients should contact Myriad’s billing department, and not their physician’s office for any insurance or billing related questions after the test is performed.
The Patient Protection Program is not available to patients covered under Medicare Part B, certain Medicaid plans, or other certain government affiliated health plans, or for those who reside in Florida, Massachusetts, Texas, Minnesota, Rhode Island, or other states where such a discount program is prohibited.
Patients can request payment plans by calling the toll-free Myriad Billing Department at 1-800-725-2722.
7. What are the options for patients without insurance coverage?
Myriad offers OnDose testing at no charge to uninsured patients who meet specific financial and medical criteria through the Myriad Financial Assistance Program. Due to regulatory limitations, patients who are recipients of government funded programs, for example Medicaid or Medicare or those that have any third-party insurance are not eligible to apply for the Myriad Financial Assistance Program.
Qualification requirements and submission instructions can be found on this site.
Myriad also offers a 25-month interest-free payment plan that enables patients to pay just $12 per test that can be set up by calling the Myriad Billing Department at 1-800-725-2722.
