STAT  investigation  of  Proove  Biosciences         Some  of  the  key  documents  STAT  obtained  as  part  of  its  investigation  are  shared   here.     1  -­‐  Proove  sales  brochure   This  Proove  brochure  offered  doctors  $30  for  each  patient  signed  up  for  a  study  of   genetic  tests  meant  to  predict  patients’  responses  to  pain  medications.  A  typical   physician  could  make  $144,000  a  year  for  “research”  that,  for  many,  involved  no   actual  work,  STAT  found.  A  separate  toxicology  study  listed  on  this  page  has  been   discontinued.     2  -­‐  Proove  legal  counsel  comments  on  HHS  fraud  alert   This  memo  written  by  Proove  Biosciences’  legal  counsel  in  2014  provides   justifications  for  company  business  operations.  It  was  drafted  in  response  to  a  2014   general  fraud  alert  from  the  US  Department  of  Health  and  Human  Services   regarding  firms  that  might  be  engaging  in  kickbacks  or  other  illegal  actions  under   the  guise  of  “research.”       3  -­‐  Patient  lab  results  example   Genetic  test  results  from  Proove  often  provide  contradictory  data.  In  one  section,   this  report  says  the  patient  should  take,  at  most,  a  greatly  reduced  dose  of  the   antidepressant  fluvoxamine  or  the  antipsychotic  drug  haloperidol.  Later  in  the   report,  detailed  results  for  metabolism  of  those  drugs  suggest  the  opposite.  They  say   the  patient  processes  both  normally.  Sources  said  many  doctors  found  such  reports   baffling  and  ignored  them.  The  document  has  been  redacted  for  patient  privacy.     4  -­‐  Proove  physician  standing  order   Physicians  sign  standing  orders  like  this  to  authorize  a  Proove  research  assistant  to   order  any  or  all  of  several  test  packages  for  any  patient  in  a  practice,  regardless  of   the  patient’s  condition.  The  doctor  is  expected  to  sign  off  on  the  testing,  but  sources   told  STAT  that  many  doctors  approved  tests    for  most  patients  regardless  of  their   diagnoses.       5  –  “Unbundled”  billing  example   This  document  shows  an  insurance  company’s  explanation  of  benefits  for  a  patient   whose  DNA  sample  was  collected  on  one  date,  but  billed  by  Proove  on  several  dates   of  service  —  a  process  called  “unbundling”  that  is  meant  to  increase  payments.  In   this  case,  the  insurer  rejected  the  claims  as  “experimental.”  The  document  has  been   redacted  to  protect  the  patient’s  privacy.     Proove Biosciences, founded in 2009, and based in Southern California, is the leader in personalized pain medicine. We provide information to improve prescribing decisions. Proove offers proprietary genetic tests to physicians that give answers to some of the doctors and patients biggest concerns. Proove's research compensation model is approved by the U.S. Inspector General's Office. Proove Biosciences: • Proove agents enroll physicians in its program to collect patient specimens in their office. We then deliver the results to the physician, allowing them to predict before prescribing. • Proprietary genetic tests identifies how patients will metabolize their medications, and risk of tolerance, dependence, or misuse to medications. Outcomes: • Treating physician maximizes patient therapy and recovery, minimizes adverse effects and prolonged conditions, providing higher level of care, while reducing medical costs and risk. • Participation will demonstrate clinical outcomes of using Proove testing and the economic impact on care, as measured by RAF scores, HCC codes , and other means to show costeffectiveness. Clinical Research Compensation: Toxicology research fees paid to Physician of $200 per hour or approximately $40 per patient are based on 12-min visits for 5 patients. For a clinic with 20 study subjects in a day, see below: Toxicology Financial Overview based on One (1) Physician Participating ~~~iiiij~ii!!iil--ll!ll:l!:!l!illllll:III:'S!I--IMIIi 4,800 Annual Tests "'"' 400 Monthly Tests $192,000 Sl6,000 s4,ooo 100 Weekly Tests 20 Daily Tests I so $800 • Annual 8 Monthly $50,000 Weekly $100,000 • Daily $150 000 $200,000 $250,000 Genetic research fees paid to Physician of $150 per hour or approximately $30 per patient are based on 12-minute visits for 5 patients. For a clinic with 20 study subjects in a day, see below: Genetic Financial Overview based on One (1) Physician Participating 4,800 Annual Tests 400 Monthly Tests 100 Weekly $144,000 _ 512 ,000 $ 3,000 Tests 20 Dally Tests $600 so $50,000 IC Annual $100,000 Monthly $150,000 $200,000 Weekly • Dally Proove will establish a clinical study protocol with Physician's and Medical Groups and have it reviewed, approved, and overseen by an independent, OHRP-Iicensed institutional review board (IRB). From Legal Counsel: On June 25, 2014, OIG published a document entitled “Special Fraud Alert: Laboratory Payments to Referring Physicians” (the “OIG Fraud Alert”). OIG identified two different types of arrangement in the health care marketplace involving alleged remuneration from clinical laboratories to referring physicians. The first arrangement addressed blood-specimen collection, processing and packaging arrangements. That type of arrangement is inapplicable to the Proove Biosciences’ PSA. The second issue raised in the OIG Fraud Alert addressed what OIG characterized as “Registry Payments.” OIG identified arrangements under which clinical laboratories are establishing, coordinating or maintaining databases, either directly or through an agent, purportedly to collect data on the demographics, presentation, diagnosis, treatment, outcomes or other attributes of patients who have undergone, or may undergo, certain tests performed by the offering laboratories. The OIG Fraud Alert calls these “Registry Arrangements.” The first point addresses OIG’s apparent suspicion about the typical Registry Arrangement. OIG stated: Laboratories that participate in Registry Arrangements often assert that they are intended to advance clinical research to promote treatment, to provide physicians with valuable clinical knowledge for patients with similar disease profiles, and to provide other benefits to physicians or the health care industry generally. Registry Arrangements may take various forms; however, they typically involve payments from laboratories to physicians for certain specified duties, including, by way of example only, submitting patient data to be incorporated into the Registry, answering patient questions about the Registry and reviewing Registry reports. OIG Fraud Alert, pp. 5-6 (emphasis added). The highlighted text suggests that OIG may not believe the physician work actually advances clinical research. On the contrary, Proove Biosciences contends its PSA is completely legitimate for the commercially reasonable business purpose to advance highly complex genetic testing research. Proove Biosciences has developed a proprietary portfolio of genetic tests that provide physicians with information necessary to improve the selection, dosing and evaluation of patients’ medications, and has undertaken significant effort to research and present data at several major scientific meetings in its field for the past two years, including meetings of the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, the American Pain Society, PainWeek, and more. In addition to presenting data at major scientific meetings, Proove Biosciences is in the midst of publishing data from its studies in peer-reviewed professional journals analyzing the efficacy of its genetic testing protocols, identifying new genetic testing clinical concepts, and developing methods to reduce health care costs and improve quality of health care by providing physicians the necessary information to genetically predict potential abuse or dependence. Proove Biosciences takes the position that it is not merely “asserting” that the data gathered by physicians subject to the PSA advances research, but the PSA is solely and exclusively designed to obtain necessary clinical data that indeed advances legitimate and highly technical clinical research. Unlike “Registries”, Proove Biosciences’ research is actually presented at major scientific meetings, is frequently published in peer-reviewed medical journals, and is intended to meet the clinical validity criteria for regulatory compliance in its filings with the Food and Drug Administration. OIG also states that the extent to which any particular Registry Arrangement violates the Anti-Kickback statute depends on the intent of the parties and adds: “Payments from a laboratory to a physician to compensate the physician for services related to data collection reporting may be reasonable in certain limited circumstances.” Proove Biosciences contends that its structure, organization and operation fits those circumstances and is reasonable and lawful. OIG identified eight specific and two general characteristics of a Registry Arrangement that may evidence an unlawful purpose. Each will be addressed separately. The OIG Fraud Alert states: “The Laboratory requires, encourages or recommends that physicians who enter into Registry Arrangements perform the tests with the stated frequency (e.g. four times per year) to be eligible to receive, or to not receive a reduction in, compensation.” OIG Fraud Alert, p. 6. Since all of Proove Biosciences’ testing involves genetic tests of DNA, all of its current testing can only be performed once during the lifetime of a patient. Therefore, Proove Biosciences never expressly or impliedly requires, states or even recommends a stated frequency of repeated tests from referring physicians. The OIG Fraud Alert states: “The laboratory collects comparative data for the Registry from, and bills for, multiple tests that may be duplicative (e.g. two or more tests performed using different methodologies that are intended to provide the same clinical information) or that otherwise are not reasonable and necessary.” Id. Proove Biosciences contends that none of its clinical laboratory tests are duplicative. The OIG Fraud Alert states: “Compensation paid to physicians pursuant to Registry Arrangements is on a per-patient or other basis that takes into account the volume or value of referrals.” Id. Proove Biosciences contends its PSA is structured in a manner that compensates the physician only for actual services rendered. Proove Biosciences’ PSA contains seven different components of services provided by physicians. Physicians are paid a flat fair market value (“FMV”) hourly rate based upon an amount established independently by Huron Consulting Services, LLC d/b/a Huron Healthcare, a nationally reputable health care valuation firm. Huron Consulting conducted a national analysis using comparable data and information to develop a range of FMV payments through various physician specialists with whom Proove Biosciences contracts. Proove Biosciences adopted the Huron Healthcare FMV analysis and included it in the PSA. The compensation structure is set in advance, and does not vary or fluctuate depending on the volume or value of referrals. Physicians, as a condition of payment, are obligated to document the services they perform and the time spent performing each service on a time sheet that is prepared by the physician, signed by the physician, submitted to Proove Biosciences and audited. Proove Biosciences contends its FMV, set-in-advance compensation paid to physicians is not a per-patient fee. Proove Biosciences contends the independent Huron Consulting expert valuation report and analysis establishes FMV payments for actual and commercially reasonable services rendered and does not take into account the actual or anticipated value or volume of referrals. In fact, Proove Biosciences currently compensates physicians who have never ordered a test from Proove Biosciences for providing various forms of clinical research services across seven categories. The OIG Fraud Alert states: “Compensation paid to physicians pursuant to Registry Arrangements is not fair market value for the physicians’ efforts in collecting and reporting patient data.” Id. Proove Biosciences contends the Huron Healthcare report establishes fair market value based upon a nationwide analysis of comparable compensation data. The OIG Fraud Alert states: “Compensation paid to physicians pursuant to Registry Arrangements is not supported by documentation, submitted by the physicians in a timely manner, memorializing the physicians’ efforts.” Id. Proove Biosciences contends its time sheet physicians must prepare documenting actual services performed on behalf of Proove Biosciences and including the time spent on such services establishes the requisite documentation memorializing the physicians’ efforts. The OIG Fraud Alert states: “The laboratory offers Registry Arrangements only for tests (or disease states associated with tests) for which it has obtained patents or that it exclusively performs.” Id. Proove Biosciences contends the proprietary portfolio of genetic tests it has developed, and the commercially reasonable need to gather clinically based data, advances its legitimate, commercially reasonable business purpose to publish studies regarding the validity, clinical efficacy, cost savings and improvement of quality of care with respect to its genetic testing protocols. Moreover, Proove Biosciences is working to refine additional tests, and expand genetic testing protocols. Through its clinical research efforts, Proove Biosciences has been conducting various clinical studies that provide it with unparalleled preparation for the new guidance issued by the Food and Drug Administration to regulate laboratory developed tests – a stated commercially reasonable purpose in its PSA. Most important, Proove Biosciences does not operate Registry Arrangements. Instead, its research protocols subject to the PSA are based upon Institutional Review Board (“IRB”) approved study protocols. Each study is reviewed, approved, and overseen by an independent, private IRB licensed by the U.S. Department of Health and Human Services’ Office of Human Research Protections (“OHRP”). A researcher who signs the Proove Biosciences’ PSA and wishes to become a study investigator must also sign a Clinical Study Rider for one of these IRB-approved protocols, and complete a certification that the researcher is qualified and not barred by the FDA from doing so. Proove Biosciences contends that its process of having all studies reviewed, approved, and overseen by a private, licensed IRB is substantively different from Registry Arrangements because it involves bona fide research consistent with OHRP standards. The OIG Fraud Alert states: “When a test is performed by multiple laboratories, the laboratory collects data only from the tests it performs.” Id. Proove Biosciences contends that for the purposes of research in the PSA, and consistent with its IRB-approved clinical study protocols, it does collect data from proprietary tests it only performs, as well as data from tests it does not perform. The OIG Fraud Alert states: “The tests associated with the Registry Arrangement are presented on the offering laboratory’s requisition in a manner that makes it more difficult for the ordering physician to make an independent medical necessity decision with regard to each test for which the laboratory will bill (e.g. disease-related panels).” Id. Proove Biosciences contends that physicians retain, and actually represent and warrant pursuant to the PSA, that they shall not refer or recommend any genetic testing or clinical diagnostic laboratory testing supplied or provided by Proove Biosciences to any patient unless the physicians have documented the medical necessity and clinical indications of the genetic testing or clinical laboratory testing. The PSA further requires physicians subject to the PSA to provide Proove Biosciences with written medical necessity and clinical documentation to justify all decisions and recommendations for genetic or clinical laboratory testing. The OIG Fraud Alert states: Other characteristics not listed above may increase the risk of fraud and abuse associated with a Registry Arrangement or provide evidence of unlawful intent. For example, the risk of fraud and abuse would be particularly high if a laboratory were to pay, and collect data for its Registry from, only a subset of physicians who are selected on the basis of their prior or anticipated referral volume, rather than their specialty, subspecialty or other relevant attribute. Id. at p. 7. Proove Biosciences contends its selection criteria for physicians offered to participate in its PSA are based upon physician specialties and subspecialties directly and extensively involved in the type of medical treatment and interventions with patients who might meet the inclusion or exclusion criteria of its IRB-approved study protocols. Proove Biosciences contends that its selection criteria do not include physicians based on their prior or anticipated referral volumes. The OIG Fraud Alert states: Even legitimate actions taken to substantiate such claims, including, for example, retaining an independent Institutional Review Board to develop study protocols and participation guidelines, will not protect the Registry Arrangement if one purpose of the arrangement is to induce or reward referrals. Id. Proove Biosciences asserts the sole and exclusive purpose of the PSA is to provide fair market value compensation to physicians for commercially reasonable clinical research services actually performed and documented by physicians to advance Proove Biosciences’ legitimate business need to obtain clinical data for purposes of conducting research that is submitted, peer-reviewed and presented at major scientific meetings, and published in peer-reviewed medical journals, and for regulatory compliance. Proove Biosciences asserts no purpose of the PSA arrangement is to pay for the referral of clinical diagnostic testing laboratory services or to induce future referrals. One other statement in the blood specimen collection portion of the OIG Fraud Alert will be addressed. It suggests that the physician cannot be paid for work performed by someone other than the physician. Proove Biosciences contends that the PSA is structured in a manner to pay exclusively for the commercially reasonable services personally performed by the physician subject to the PSA. Based on the foregoing, Proove Biosciences contends that its PSA arrangement with referring physicians is lawful and does not involve the suspicious characteristics articulated in the OIG Fraud Alert. A recently published federal court decision dismissing alleged violations of the Anti-Kickback statute establishes the legal context of the OIG’s Fraud Alert, as follows: OIG Advisory Opinions do not establish rules of decision, and are not to receive judicial deference. ***** OIG’s identification of a practice as “suspect” merely triggers further investigation by OIG; it does not render a practice per se illegal or unlawful. U.S. ex rel. McDonough v. Symphony Diagnostic Services, Inc., ____ F.Supp.2d ____ (S.D. Ohio 2014) (2014 WL 3906461). Accordingly, an OIG Fraud Alert technically is not the law and a “suspect” practice identified by OIG does not render an arrangement per se illegal or unlawful. Nevertheless, Proove Biosciences takes the OIG Fraud Alert quite seriously and invests significant resources in its efforts to comply with all federal laws and regulations.   Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) v.4 Report Date 2015 Patient Information Patient Name Date of Birth Ethnicity Gender Pain Medications Male Standard Precaution Date of Service 2015 Customer ID Date Received by Laboratory 2015 Account Name Date of Injury N/A Physician Name Caution Non-Opioids Carbamazepine (Tegretol) Carisoprodol (Soma) Cyclobenzaprine (Flexeril) Gabapentin (Neurontin) Opioids Buprenorphine (Butrans) Fentanyl (Duragesic) Hydromorphone (Dilaudid) Methadone (Dolophine) Morphine (MS Contin, Avinza) Oxymorphone (Opana) Tapentadol (Nucynta) Hydrocodone (Norco, Vicodin) NSAIDs Celecoxib (Celebrex) Diclofenac (Voltaren) Etodolac (Lodine) Flurbiprofen (Ansaid) Ibuprofen (Advil, Motrin) Indomethacin (Indocin) Ketoprofen Ketorolac (Toradol) Meclofenamate (Meclomen) Mefenamic acid (Ponstel) Meloxicam (Mobic) Nabumetone (Relafen) Naproxen (Naprosyn, Aleve) Oxaprozin (Daypro) Piroxicam (Feldene) Tolmetin sodium (Tolectin) Fenoprofen (Nalfon) Benzodiazepines Alprazolam (Xanax) Bromazepam (Lexotanil) Clonazepam (Klonopin) Diazepam (Valium) Flurazepam (Dalmane) Midazolam (Versed) Temazepam (Restoril) Triazolam (Halcion) Lorazepam (Ativan) Oxazepam (Serax) Extreme Caution Codeine Oxycodone (OxyContin, Percocet) Tramadol (Ultram) Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P v3.0.0a3.0.0 Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 1 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: Psychotropics Standard Precaution Caution Extreme Caution SSRIs Sertraline (Zoloft) Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac) Fluvoxamine (Luvox) Paroxetine (Paxil) SNRIs Desvenlafaxine (Pristiq) Levomilnacipran (Fetzima) Duloxetine (Cymbalta) Venlafaxine (Effexor) Amitriptyline (Elavil) Desipramine (Norpramin) Doxepin (Sinequan) Imipramine (Tofranil) Nortriptyline (Pamelor) Tricyclic Antidepressants Atypical Antidepressants Bupropion (Wellbutrin) Vilazodone (Viibryd) Typical Antipsychotics Thiothixene (Navane) Atypical Antipsychotics Asenapine (Saphris) Lurasidone (Latuda) Paliperidone (Invega) Quetiapine (Seroquel) Ziprasidone (Geodon) Mirtazapine (Remeron) Nefazodone (Serzone) Trazodone (Oleptro) Vortioxetine (Brintellix) Chlorpromazine (Thorazine) Fluphenazine (Prolixin) Haloperidol (Haldol) Perphenazine (Trilafon) Thioridazine (Mellaril) Olanzapine (Zyprexa) Aripiprazole (Abilify) Iloperidone (Fanapt) Pimozide (Orap) Risperidone (Risperdal) Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 2 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: Pain Medications — Detailed Results & Recommendations Non-Opioids Carbamazepine (Tegretol) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Carisoprodol (Soma) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Cyclobenzaprine (Flexeril) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Gabapentin (Neurontin) Gabapentin is not appreciably metabolized by the CYP450 family of enzymes; therefore, no dosage changes based on CYP450 genetics are recommended. However, if this patient requires concomitant treatment with opioids, (s)he may experience increases in gabapentin concentrations. In this case, carefully observe for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression, and reduce the dose of gabapentin or opioids appropriately. Reduction of gabapentin dose may also be required in patients who have age-related compromised renal function. Opioids Codeine This patient may experience insufficient pain relief due to decreased metabolism to morphine. Consider prescribing an alternative medication not metabolized by CYP2D6. Oxycodone (OxyContin, Percocet) This patient may experience insufficient pain relief with average doses of Oxycodone due to decreased metabolism to oxymorphone. Monitor the patient's analgesic response and consider prescribing an increased dose if necessary or select alternative medication. Tramadol (Ultram) This patient may experience insufficient pain relief with average doses of Tramadol due to decreased metabolism to active drug. Consider alternative medication (not oxycodone or codeine). Hydrocodone (Norco, Vicodin) This patient may experience insufficient pain relief with average doses of Hydrocodone due to decreased metabolism to hydromorphone. Monitor the patient's analgesic response and consider prescribing an alternative medication not metabolized by CYP2D6 if necessary. Buprenorphine (Butrans) This patient is predicted to be a normal metabolizer of buprenorphine. Prescribe at standard label recommendations. Fentanyl (Duragesic) This patient is predicted to be a normal metabolizer of Fentanyl. Prescribe at standard label recommendations. Hydromorphone (Dilaudid) This patient is not predicted to have abnormal metabolism of Hydromorphone. Prescribe at standard label recommendations. Methadone (Dolophine) This patient is predicted to require an average methadone maintenance treatment dose. Morphine (MS Contin, Avinza) This patient is not predicted to have abnormal metabolism of Morphine. Prescribe at standard label recommendations. Oxymorphone (Opana) This patient is not predicted to have abnormal metabolism of oxymorphone. Prescribe at standard label recommendations. Tapentadol (Nucynta) This patient is not predicted to have abnormal metabolism of Tapentadol. Prescribe at standard label recommendations. Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 3 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: Pain Medications — Detailed Results & Recommendations NSAIDs Fenoprofen (Nalfon) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider a reduction of recommended starting dose and/or reducing frequency of use. Celecoxib (Celebrex) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Diclofenac (Voltaren) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Etodolac (Lodine) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Flurbiprofen (Ansaid) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Ibuprofen (Advil, Motrin) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Indomethacin (Indocin) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Ketoprofen This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Ketorolac (Toradol) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Meclofenamate (Meclomen) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Mefenamic acid (Ponstel) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Meloxicam (Mobic) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Nabumetone (Relafen) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Naproxen (Naprosyn, Aleve) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Oxaprozin (Daypro) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Piroxicam (Feldene) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Tolmetin sodium (Tolectin) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 4 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: Pain Medications — Detailed Results & Recommendations Benzodiazepines Lorazepam (Ativan) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Oxazepam (Serax) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Alprazolam (Xanax) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Bromazepam (Lexotanil) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Clonazepam (Klonopin) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Diazepam (Valium) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Flurazepam (Dalmane) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Midazolam (Versed) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Temazepam (Restoril) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Triazolam (Halcion) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 5 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: Psychotropics — Detailed Results & Recommendations SSRIs Fluvoxamine (Luvox) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider a 25-50% reduction of recommended starting dose and titrate to response, or use an alternative medication not predominantly metabolized by CYP2D6. Paroxetine (Paxil) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider an alternative medication not predominantly metabolized by CYP2D6. If paroxetine use is warranted, consider a 50% reduction of recommended starting dose and titrate to response. Citalopram (Celexa) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Escitalopram (Lexapro) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Fluoxetine (Prozac) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Please note: according to the FDA Drug Label, if fluoxetine is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need for decreased dose of the original medication should be considered. Drugs with a narrow therapeutic index represent the greatest concern (e.g., flecainide, propafenone, vinblastine, and TCAs). Sertraline (Zoloft) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. SNRIs Venlafaxine (Effexor) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider a reduction of recommended starting dose and titrate to response, or choose an alternative medication. Duloxetine (Cymbalta) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Desvenlafaxine (Pristiq) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Levomilnacipran (Fetzima) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Tricyclic Antidepressants Amitriptyline (Elavil) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Avoid tricyclic use. If a tricyclic is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustment. Desipramine (Norpramin) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Avoid tricyclic use. If a tricyclic is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustment. Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 6 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: Psychotropics — Detailed Results & Recommendations Tricyclic Antidepressants Doxepin (Sinequan) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Avoid tricyclic use. If a tricyclic is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustment. Imipramine (Tofranil) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Avoid tricyclic use. If a tricyclic is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustment. Nortriptyline (Pamelor) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Avoid tricyclic use. If a tricyclic is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustment. Atypical Antidepressants Vortioxetine (Brintellix) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider a lower dose if indicated or select an alternative medication. FDA Drug Label indicates of 10mg/day is the maximum recommended dose for CYP2D6 poor metabolizers. Mirtazapine (Remeron) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Nefazodone (Serzone) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Trazodone (Oleptro) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Bupropion (Wellbutrin) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions and consider therapeutic drug monitoring to achieve a hydroxybupropion level between 850 and 1500 ng/ml. Vilazodone (Viibryd) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Typical Antipsychotics Chlorpromazine (Thorazine) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider a reduction of recommended starting dose and titrate to response. Fluphenazine (Prolixin) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider a reduction of recommended starting dose and titrate to response. Haloperidol (Haldol) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider a 50% reduction of recommended starting dose and titrate maintenance dose in response to haloperidol plasma concentration, or choose an alternative medication. Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 7 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: Psychotropics — Detailed Results & Recommendations Typical Antipsychotics Perphenazine (Trilafon) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider a reduction of recommended starting dose and titrate to response, or choose an alternative medication not predominantly metabolized by CYP2D6. Thioridazine (Mellaril) This medication is contraindicated in patients with reduced CYP2D6 activity due to potentially fatal side effects. Thiothixene (Navane) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Atypical Antipsychotics Aripiprazole (Abilify) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider reducing maximum dose to 10mg/day (67% of the maximum recommended daily dose) or choosing an alternative medication. Iloperidone (Fanapt) This patient has a complex genotype with potential for decreased metabolism of this medication. Consider a 50% reduction of recommended starting dose and titrate to response, or select an alternative medication. Pimozide (Orap) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Doses should not exceed 0.05mg/kg/day in children or 4 mg/day in adults and doses should not be increased earlier than 14 days. Risperidone (Risperdal) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Consider a reduction of recommended starting dose and titrate to response, or use an alternative medication not predominantly metabolized by CYP2D6. Olanzapine (Zyprexa) This patient is at risk of experiencing an adverse drug event with this medication due to decreased metabolism. Initiate standard recommended dose, but consider lower maintenance dose if indicated. Asenapine (Saphris) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Lurasidone (Latuda) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Paliperidone (Invega) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Quetiapine (Seroquel) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Ziprasidone (Geodon) This patient is predicted to metabolize this medication normally. Prescribe with standard precautions. Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 8 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: Enzyme Metabolizer Status Genetic Variation Results CYP 1A2 Normal *1M *1Q/*1M *1Q CYP 2C8 Normal *1/*1 CYP 2C9 Normal *1/*1 CYP 2C19 Normal *1/*1 CYP 2D6 Deficient (*4/*5)1N CYP 3A4 Normal *1/*1 CYP 3A5 Deficient *3/*3 Medications Drug-Drug Interactions amitriptyline, clomipramine, imipramine, clozapine, olanzapine,haloperidol, caffeine, ropivacaine, theophylline, zolmitriptan,melatonin, tamoxifen, erlotinib, cyclobenzaprine, fluvoxamine,naproxen, ondansetron, phenacetin, paracetamol/acetaminophen, propranolol, tizanidine, warfarin amodiaquine, cerivastatin, paclitaxel, repaglinide, torasemide, sorafenib, rosiglitazone, buprenorphine Inhibited by fluoroquinolones, fluvoxamine, caffeine, Sr. John’s Wort Induced by tobacco, omeprazole NSAIDs (celecoxib, ibuprofen, diclofenac, etc.), sulfonylureas, angiotensin II receptor antagonists, sildenafil, phenytoin, fluvastatin, fluoxetine, ketamine, rosiglitazone, THC, tamoxifen antidepressants (SSRIs, TCAs), amitriptyline, antiepileptics, PPIs, clopidogrel, propranolol, carisoprodol, indomethacin, progesterone, warfarin opioids (hydrocodone, codeine, tramadol), antidepressants (SSRIs, TCAs, venlafaxine, mianserin, minaprin), beta-blockers, amitriptyline, antipsychotics, Class I antiarrhythmics, amphetamine, atomoxetine, duloxetine, metoclopramide, phenacetin opioids (alfentanil, buprenorphine, fentanyl, methadone, levacetylmethadol, oxycodone), immunosuppressants (cyclosporine, tacrolimus, sirolimus), chemotherapies (docetaxel, tamoxifen, paclitaxel, imatinib, cyclophosphamide, doxorubicin, erlotinib, etoposide, ifosfamide, teniposide, gefitinib, vinblastine, vincristine, vindesine, sunitinib, irinotecan, sorafenib, vemurafenib, temsirolimus, anastrozole) macrolides, tricyclics, antidepressants (amitriptyline, clomipramine, imipramine, cyclobenzaprine, citalopram, norfluoxetine, sertraline, mirtazapine, nefazodone, reboxetine, venlafaxine, trazodone), antipsychotics, benzodiazepines, statins, calcium channel blockers, glucocorticoids, domperidone Inhibited by antifungals, valproic acid, lovastatin, fluvastatin, sertraline Induced by secobarbital and rifampicin Inhibited by gemfibrozil, trimethoprim Induced by rifampicin Inhibited by moclobemide and fluvoxamine Induced by carbamazepine, aspirin, prednisone, rifamipicin Inhibited by SSRI, bupropion, sertraline, duloxetine, buprenorphine, antipsychotics, methadone, celecoxib Induced by dexamethasone, rifampicin, glutethimide Inhibited by protease inhibitors, some macrolides, nefazodone, someantifungals, buprenorphrine, fluoxetine Induced by anticonvulsants, barbiturates, St. John’s Wort, modafinil Metabolizer Status Reference Guide Accelerated Metabolizer Compromised Metabolizer Accelerated or Normal Metabolizer Compromised or Deficient Metabolizer Normal Metabolizer Deficient Metabolizer Normal or Compromised/Deficient Metabolizer Insufficient Lab Results Proceed with Standard Precautions (Undefined Significance) Proceed with Caution (Abnormal Metabolizer) Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 9 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: Enzyme Metabolizer Status Genetic Variation Results CYP 2B6 Normal rs3745274: G/G UGT2B7 Decreased rs6600880: A/A rs6600879: G/G rs7668282: T/T rs7668258: C/C UGT2B15 Compromised rs1902023: A/C V KORC1 Normal *1/*4 Medications Drug-Drug Interactions alfentanil, bupropion, cyclophosphamide, efavirenz, methadone, nevirapine, propofol, sertraline, sorafenib, tamoxifen, valproic acid, methoxetamine, ketamine almokalant, atorvastatin, buprenorphine, carvediolol, chloramphenicol, codeine, cyclosporine, diclofenac, entacapone, epirubicin, febuxostat, fenofibrate, fenoprofen, fluvastatin, gemfibrozil, hydromorphone, ibuprofen, ketoprofen, lamotrigine, lorazepam, methadone, morphine, mycophenolate, nalorphine, naloxone, naltrexone, naproxen, nicotine, oxycodone, simvastatin, tacrolimus, temazepam, valproic acid, zidovudine Tamoxifen, S-oxazepam, lorazepam, dabigatran, R-methadone, valproic acid, efavirenz, acetaminophen, sipoglitazar warfarin Inhibited by orphenadrine Induced by carbamazepine, phenobarbital, phenytoin Inhibited by ketoconazole and valproic acid Induced by barbiturates Inhibited by Phenytoin, phenobarbital, valproic acid Induced by Rifampicin, estrogen, cruciferous vegetables, soy foods, citrus fruits Anticoagulants, Antiplatelet Agents, NSAIDs, and Serotonin Reuptake Inhibitors can increase the risk of bleeding when used concomitantly with Warfarin. Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the exposure of Warfarin Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the exposure of Warfarin. V itamin-K containing foods or supplements may decrease the efficacy of Warfarin. Metabolizer Status Reference Guide Accelerated Metabolizer Compromised Metabolizer Accelerated or Normal Metabolizer Compromised or Deficient Metabolizer Normal Metabolizer Deficient Metabolizer Normal or Compromised/Deficient Metabolizer Insufficient Lab Results Transporter Activity Genetic Variation Results ABCB1 Normal rs1128503: A/G rs2032582: A/C rs1045642: A/G OCT1 Normal rs622342: A/A Proceed with Standard Precautions (Undefined Significance) Proceed with Caution (Abnormal Metabolizer) Report ID: undefined Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 10 of 11 Proof of Drug Metabolism Proove Drug Metabolism Profile (PBIO2) Patient Name: The Proove Promise We promise to respect the dignity and recognize the merit of individuality. Many define individual health from the perspective of the “average” treatment, doctor, or patient, assuming that the statistical average predicts the individual outcome. The average is a myth. There is no “average” treatment, doctor, patient or person for that matter. We believe in the power of one – one company, one doctor, one patient – to make a difference. Individuality is our reality. Brian Meshkin President, CEO Si V an Nguyen, M.D., F.C.A.P Laboratory Director Mehrdad Zoleikhaeian, CGMBS, MB(ASCP) CM Vice President of Lab Operations Limitations This test does not detect all the known gene mutations that result in altered or inactive enzymatic activity. A “normal” genetic report indicates only the absence of the mutations evaluated, and does not imply that other mutations are not present. This assay is not designed to detect all the known variants that result in altered enzymatic activity. Therefore, absence of a detectable gene variant or polymorphism does not rule out the possibility that a patient has an altered metabolizer phenotype due to the presence of an undetected polymorphism or due to drug-drug interactions. DNA testing does not replace the need for clinical evaluation and therapeutic drug monitoring. The CYP2D6*1 allele is characterized by the absence of any sequence variations. Consequently, this allele cannot be identified by a single SNP assay; rather, CYP2D6*1 is assigned by default when no mutant SNPs are detected during testing. CYP2D6*2 is a ‘default’ assignment and, unless tested and discriminated, includes the variants CYP2D6*8, *11, *19, *42, *45, *46, among others. CYP2D6*2A or *21 is a ‘default’ assignment and, unless tested and discriminated, includes the rare variants CYP2D6**31,*51,*56A. CYP2D6*10 or *36 is a ‘default’ assignment, and unless tested and discriminated, includes the rare variants CYP2D6 *47, *49, *54, *56B, *57, *72, among others. CYP2D6*17 is a ‘default’ assignment and, unless tested and discriminated, includes the rare variants CYP2D6*40 and *58. CYP2D6*39 is a ‘default’ assignment and, unless tested and discriminated, includes the rare variants CYP2D6*56, *83, and *88. "CYP1A2*1A is a 'default' assignment that includes the rare variants *1C, *4, and *11. CYP1A2*1B is a 'default' assignment that includes the rare variants *1b,*1g,*1h,*1s,*1t,*1u,*3,*8,*15,*16,*18,*19,*20. CYP1A2*1B is assumed a normal functioning variant of the cytochrome. The CYP1A2*1F assignment includes the rare variant *1K. The CYP1A2*1L *1N assignment includes the rare variants *1P, *1R, *21. Methodology Genomic DNA is isolated from a dry buccal swab using a commercially available magnetic particle DNA isolation kit along with proprietary techniques using an automated DNA isolation system. Specific regions of interest are amplified using commercially available proprietary primers, TaqMan® probes, and reagents from Life Technologies, a ThermoFisher Company. The variants are detected on Life Technologies QuantStudio 12k Flex genetic analyzer as Single Nucleotide Polymorphisms (SNPs). The data is analyzed and reported by qualified licensed laboratory personnel using Life Technologies Genotyper data analysis software, version 1.3. This test was independently verified by Proove Biosciences, Inc. (Irvine, California) under Clinical Laboratory Improvement Amendment (CLIA) guidelines as a Laboratory Developed Test (LDT). Disclaimer The above test(s) have not been cleared or approved by the US Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. Proove Medical Laboratories, Inc., has validated the performance characteristics of the above test(s). The above test(s) results are not intended to be used as the sole means for clinical diagnoses or patient management decisions. Only medically necessary tests (based on specific patient diagnosis and treatment) should be ordered. Screening tests will generally not be reimbursed by third party carriers. Laboratory Director: S. Nguyen, M.D., F.C.A.P Proove Biosciences, Inc. · Proove Medical Laboratories, Inc. 26 Technology Drive East, Irvine, CA 92618 · Ph. (855) 776-6832 · Fax (888) 971-4219 · www.proove.com CA State Lab ID No: CLF 4478 CLIA No: 05D0580755 Page 11 of 11         ATTENTION  Physician/  Provider:  Please  feel  free  to  use  the  document  below  as  an  example  template  for  preparing  your   clinic’s  Standing  Order  for  all  Proove  Biosciences  Genetic  Laboratory  Testing.    The  purpose  of  this  letter  is  to   establish  and/or  clarify  which  Proove  Genetic  Tests  you  would  like  your  patients  to  receive.  Consider  your  patient   population  as  a  whole  when  deciding.    Using  your  company  or  personal  letterhead,  please  create  and  edit  this   letter  as  you  see  fit;  however,  please  do  NOT  edit  the  last  paragraph.  This  document  does  NOT  replace  any  other   required  documentation  for  ordering  Proove  Genetic  Testing.  All  Proove  Genetic  Tests  must  be  approved  and   ordered  by  the  patient’s  provider.  Please  contact  Rhonda  Smith  (949-­‐734-­‐7279;  rfsmith@proovebio.com)  if  you   have  any  questions.   __________________________________________________________________________________________________     {Date}     ATTN:  Mehrdad  Zoleikhaenian,  CGMBS,  MB  (ASCP)   VP  of  Laboratory  Operations   Proove  Medical  Laboratories,  Inc.   26  Technology  Drive  East,  Irvine,  CA  92618   mzoleikhaeian@proovebio.com     Dear  Mehrdad  Zoleikhaenian:     For  patients  under  my  care,  I  hereby  authorize  my  staff,  including  any  other  physicians  (MDs  or  DOs),  physician   assistants  (PAs),  nurse  practitioners  (NPs),  nurses  (RNs),  medical  assistant  (MAs)  or  a  clinical  research  assistant  from   Proove  Biosciences,  Inc.  to  perform  the  following  tests:    Proove  Drug  Metabolism  Profile  on  all  patients  who  are  candidates  for  or  currently  taking  prescription  medication   under  my  care;   Proove  Opioid  Risk  Profile  on  all  patients  who  are  candidates  for  or  currently  taking  opioid  pain  medications  under   my  care;     Proove  Pain  Perception  Profile  on  all  patients  who  are  currently  experiencing  pain;   Proove  Opioid  Response  (including  Hydrocodone,  Oxycodone,  Morphine,  Tramadol,  and  Hydromorphone)  Profiles  on   all  patients  who  are  candidates  for  or  currently  taking  those  opioid  pain  medications  under  my  care;   Proove  Non-­‐Opioid  Response  (including  Ibuprofen,  Gabapentin,  Alprazolam,  and  Acetaminophen)  Profiles  on  all   patients  who  are  candidates  for  or  currently  taking  those  non-­‐opioid  pain  medications  under  my  care;  and   Proove  NSAID  Risk  Profile  on  all  patients  who  are  candidates  for  or  currently  taking  NSAID  medications.   I  understand  that  I  will  review  each  patient’s  medical  record  and  physical  exam  to  determine  medical  necessity,  and  I   will  attest  to  that  medical  necessity  of  each  individual  patient’s  test  requisition  form  and  a  daily  testing  log  of  all  tests   performed  each  clinic  day.       Sincerely,     {Provider  Signature}       AI?Itl?Iem BB.IUII I and HeaIth I 2a I I I Dizzignesis: are not covered ace rating I. requeeted service isfdenied. The request for authorizatio I Medical Reviewer, teets to see how youIr body testing for pelymorphisms).I oi the panel not :ahIow that these tests are I dependence) as wagwant you to Iun-Ierstan-CII.? you. IheaIl?I Coverage, for the . ?h'IecIImi w: i . I- I I Investigaticmal for on1. We b'I' Polyn'mrphisn?Is Io DeIeItmm-Ielhutl - the twername mi hear the E3IUEI CH1 MAB Anthea Se010-: 77forl the06.! requIeet tea. "i been deter? . II dth.I Ah- II- 4?mule . iA?v- I I..- .. ~31lthers. Our term: we do not determ??! 6 too I Your provider ma call em. Com/ca TO reques eter ination ple . for services th tElE i . *r fare is Covered Ullder thEe memberSI ii E3157 5 is EEW 1' - teIIur definition of medical necessi - r30! 7 at ou con ultwith and/0? "9am" your ?ea" I Prlate for you Treatment deoISIon . . only addresses the availabIlIty ofIPl . radically necessary, benefits will nothep; . . should have avail El edical rewewer at 300 794 0838 to disc I -. 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