Persius/imr-appeals huggingface dataset:
Appeal type: Experimental
Decision: Upheld

Summary Reviewer 3

A 54-year-old male has requested reimbursement for genetic testing performed on 2/04/16. The Health Insurer has denied this request indicating that the services at issue were considered investigational for evaluation of the enrollees colon cancer.The physician reviewer found that patients with refractory or relapsed cancer that have exhausted standard treatments are usually considered for clinical trials. Recently, it has become important to identify mutations that may be amenable to targeted therapy. Von Hoff and colleagues performed a study of 86 patients where the progression-free survival on the regimen selected by molecular profiling was compared to the progression-free regimen on the last chemotherapy regimen. The regimen selected by molecular profiling offered a 27% survival advantage. Genetic testing may be highly informative. For example, KRAS and BRAF mutations may inform therapy decisions. KRAS is one of the most frequently mutated oncogenes in colorectal cancer (35-45% of patients).  The gain of function mutations most commonly occur in codon 12 or codon 13.  In several clinical trials, mutation in KRAS is associated with worse progression-free survival compared to patients with wild type KRAS when treated with monoclonal antibody directed against EGFR in combination with chemotherapy.  In one large randomized clinical trial where FOLFIRI was tested with or without Erbitux, KRAS mutation status did not significantly affect progression-free survival. There is published data from a large retrospective trial that the presence of the BRAF mutation provides additional prognostic information with regards to cetuximab treatment. The MEK kinases are within the same pathway as RAS and BRAF. Mekinist or trametinib is a new inhibitor of MEK kinases approved for use in metastatic melanoma with mutant BRAF.  In this patients case, the results from molecular profiling offers a rational selection of the next regimen. Thus, genetic testing performed on 2/04/16 was likely to have been more efficacious than other standard methods of evaluating this patient. Based upon the information set forth above, the services at issue were likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. The Health Insurers denial should be overturned.
Appeal type: Experimental
Decision: Overturned

Summary Reviewer 1

The parent of an 11-year-old female enrollee has requested authorization and coverage for gene testing.  The Health Insurer has denied this request indicating that the requested services are considered investigational for evaluation of the enrollees medical condition. The physician reviewer found the current medical evidence supports the requested services in this clinical setting.  Depending on which type of genetic mutation she has, this patients management may vary greatly and have an impact on her bone health and renal failure.  While neither syndrome can be reversed, the effects can be mitigated and modulated with appropriate therapy.  It is not possible to determine what type of syndrome to treat without genetic testing.  Whole exome sequencing is sensitive and specific and identifies changes in the DNA that are causative for the medical conditions, in contrast to current sequencing tests that analyze one gene or small groups of related genes.  If a mutation is identified, targeted medical care may be recommended and other testing can be avoided.  Whole exome sequencing would allow for genotype-phenotype correlation and allow therapy to be tailored accordingly.  All told, the requested gene testing is likely to be of greater benefit than other methods of evaluating this patient.  Based upon the information set forth above, the requested services are likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. The Health Insurers denial should be overturned.
Appeal type: Experimental
Decision: Upheld

Summary Reviewer 3

A 45-year-old female enrollee has requested reimbursement for FoundationOne CDx testing performed on 1/29/19. The Health Insurer has denied this request and reported that the services at issue were investigational for the evaluation of the enrollees medical condition. The physician reviewer found that the metastatic carcinoid or neuroendocrine tumor is a rare cancer that is generally not responsive to cytotoxic chemotherapy. There are studies trying single agents and combination therapy, but response rates are poor. There is no standard therapy, and it is preferable that patients be enrolled into a clinical protocol. In this case, the patients unusual tumor was submitted to Foundation Medicine for molecular testing to identify mutations that may be amenable to targeted therapies. Recently, it has become important to identify mutations that may be amenable to targeted therapy. Von Hoff and colleagues performed a study of 86 patients, and the progression-free survival on regimen selected by molecular profiling was compared to progression-free survival on the last
chemotherapy regimen. The regimen selected by molecular profiling offered a 27% survival advantage. All told, FoundationOne CDx testing performed on 1/29/19 was likely to have been more beneficial than other methods of evaluating this patient.
Appeal type: Experimental
Decision: Overturned

Summary Reviewer 2
A 66-year-old female enrollee has requested authorization and coverage for ablation of varicose veins, right and left accessory ablation.  The Health Insurer has denied this request indicating that the requested services are considered investigational for treatment of the enrollees medical condition. The physician reviewer found that there is sufficient support for the requested services in this clinical setting.  Patients with anterior accessory saphenous vein reflux and patients with the great saphenous vein reflux demonstrate similar disease-specific features.  Following great saphenous veins ablation, persistent non-refluxing branches do not appear to have an adverse impact on clinical outcome two years after successful ablation of the great saphenous vein.  Although there is limited clinical data to recommend ablation of the non-axial veins, the published data suggest it is effective in selected patients.  There is evidence to support sclerotherapy in the treatment of accessory recurrent varicose veins following ablation.  Thus, ablation of varicose veins, right and left accessory ablation is likely to be more effective than other treatment options.  Based upon the information set forth above, the requested services are likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Insurers denial should be overturned.
Appeal type: Experimental
Decision: Upheld

Summary Reviewer 2 
 
A 62-year-old male enrollee has requested reimbursement for genetic testing performed on 
9/29/20. The Health Insurer has denied this request and reported that the services at issue were 
investigational for the evaluation of the enrollees medical condition. At issue is whether the 
services at issue were likely to have been more beneficial for evaluation of the enrollee's condition 
than any available standard therapy. The physician reviewer found that several studies have 
evaluated tumor markers in cutaneous squamous cell carcinoma and identified associations with 
aggressive tumors. As the composite definition of high-risk cutaneous squamous cell carcinoma 
remains unclear, the identification of reliable biomarkers is particularly promising in aiding the 
recognition of patients at risk for poor outcomes and guiding clinical disease management. 
DecisionDx-SCC is a 40-gene expression profile test that has been developed to stratify patients 
with high-risk cutaneous squamous cell carcinoma into three classes based on the three-year 
metastasis risk. Per the article by Farberg and colleagues, the integration of the gene expression 
profile with the American Joint Committee on Cancer 8 (AJCC 8)  and the Brigham and Womens 
Hospital (BWH) staging systems identified a subgroup of 24 patients at very high risk of metastasis 
(16 of whom were T1/T2 according to the AJCC 8 and 17 of whom were T1/T2a according to the 
BWH staging system) who would benefit from high-intensity management. Conversely, subgroups 
of patients classified as AJCC 8 T3/T4 or BWH T2b/T3 were assigned to class 1 based on their 
risk of metastasis. These patients would have been appropriately managed with low-intensity 
treatment. Currently, high-risk is largely defined by tumor size and region of disease. The standard 
of care is to use clinical factors to decide risk. However, the services at issue were likely to have 
been of additional benefit. Therefore, the genetic testing performed on 9/29/20 was likely to have 
been more beneficial than any available standard therapy.
Appeal type: Experimental
Decision: Overturned

Summary Reviewer 2


A 57-year-old female enrollee has requested reimbursement for digital breast tomosynthesis performed on 9/01/16.  The Health Insurer has denied this request indicating that the service at issue was considered investigational for evaluation of the enrollees medical condition. The physician reviewer found that breast tomosynthesis provides advantages to radiologists interpreting mammograms, especially in women with dense tissue.  This tomographic method often allows the reader to separate dense glandular elements from underlying mass/architectural distortion and results in decrease callbacks and increase overall diagnostic accuracy and detection of small cancers compared to two-dimensional mammography alone.  Thus, the addition of breast tomosynthesis to the usual two-dimensional mammographic protocol was likely of greater benefit to the patient than had her mammogram been done with two-dimensional imaging alone.  Based upon the information set forth above, the service at issue was likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. The Health Insurers denial should be overturned.
Appeal type: Experimental
Decision: Upheld

Summary Reviewer 1

A 50-year-old male enrollee has requested authorization and coverage for transcatheter insertion of permanent leadless implantable pacemaker. The Health Insurer has denied this request and reported that the requested services are investigational for the treatment of the enrolleeas medical condition. The physician reviewer found that the accepted indications for leadless pacemakers generally include younger patients, those with difficult venous access or other anatomical issues, making transvenous placement or pocket creation problematic, certain sports or work-related use of the upper extremity where long-term lead trauma might be expected and absence of need for dual chamber pacing, such as permanent atrial fibrillation. This patient has none of these indications. Moreover, uncertainties exist about the long-term clinical outcomes associated with leadless pacemakers because most studies only report acceptable pacing capture thresholds as the primary efficacy endpoint. Therefore, transcatheter insertion of permanent leadless implantable pacemaker is not likely to be more beneficial than any available standard therapy.
Appeal type: Experimental
Decision: Overturned

Summary Reviewer 1

The parent of a five-year-old male enrollee has requested reimbursement for gene testing performed on 11/20/15. The Health Plan has denied this request indicating that the testing at issue was considered investigational for evaluation of the enrollees generalized epilepsy of unknown etiology. The physician reviewer found the clinical utility of CMA is well established in the peer-reviewed literature and is considered first-line genetic tests for individuals with developmental delays and autism spectrum disorders according to the American Academy of Pediatrics (AAP) and the American College of Medical Genetics (ACMG) (Schaefer, et al; Moeschler, et al).  Olson and colleagues evaluated the role of copy number variation (CNV) abnormalities detectable using CMA testing in patients with epilepsy. The authors found that in at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or hotspots. Copy number abnormalities were found to play an important role in patients with epilepsy. The authors concluded that because the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy. Similarly, Striano and colleagues compared 279 patients with unexplained epilepsy to patients with non-syndrome intellectual disability and healthy controls using CMA. The authors found that patients with epilepsy show a significantly increased burden of large, rare, gene-rich CNVs. Several specific (ion channel) genes were noted to have a specific association between the identified CNVs and epilepsy (Striano, et al). Moreover, CMA has been shown to provide clinically actionable information with results influencing medical care by precipitating medical referrals, diagnostic imaging, and specific laboratory testing (Coulter, et al). For the reasons provided, the gene testing performed on 11/20/15 was likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. Based upon the information set forth above, the testing at issue was likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. The Health Insurers denial should be overturned.
Appeal type: Experimental
Decision: Overturned

Summary Reviewer 3

A 62-year-old female enrollee has requested reimbursement for the ThyGenX Thyroid Oncogene Panel testing provided on 11/18/15. The Health Insurer has denied this request indicating that the testing at issue was considered investigational for evaluation of the enrollees thyroid nodule. The physician reviewer found that thyGenX testing is generally considered standard protocol on all FNA samples taken on thyroid nodules. There is sufficient peer-reviewed medical literature demonstrating that this test can be easily performed and can help avoid needless surgeries. In this patients case, the initial biopsy results were indeterminate, and the ThyGenX testing results prevented the patient from having to undergo an unnecessary surgery. All told, the ThyGenX Thyroid Oncogene Panel testing provided on 11/18/15 was likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. Based upon the information set forth above, the testing at issue was likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. The Health Insurers denial should be overturned.
Appeal type: Experimental
Decision: Upheld

Summary Reviewer 3

A 56-year-old male enrollee has requested reimbursement for des-gamma-carboxy prothrombin (DCP) testing performed on the enrollee on 5/29/15. The Health Insurer has denied this request indicating that the service at issue was considered investigational for evaluation of the enrollees medical condition. The physician reviewer found that patients with cirrhosis are at risk for hepatocellular carcinoma (Mancebo, et al).  Guidelines from the American Association for the Study of Liver Disease (AASLD) recommend screening every six months in patients with cirrhosis due to the risk of developing hepatocellular carcinoma (Bruix and Sherman). Surveillance ultrasound and alpha-fetoprotein (AFP), which are screening modalities for hepatocellular carcinoma in patients with cirrhosis, have sensitivities of only 44% and 66%, respectively (Singal, et al). Clinical studies show that hepatocellular carcinoma can present with positive AFP, AFP subtype L3, or des gamma carboxy prothrombin (DCP) with only some overlap (Li and Satomura). DCP is an effective marker for the development and progression of hepatocellular carcinoma (Durazo, et al; Yuen and Lai).  For these reasons, the DCP testing performed on 5/29/15 was likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. Based upon the information set forth above, the services at issue were likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. The Health Insurers denial should be overturned.
Appeal type: Experimental
Decision: Upheld

Summary Reviewer 2


A 30-year-old female enrollee has requested reimbursement for the Anser ADA serological markers performed on 8/21/15. The Health Insurer has denied this request indicating that the testing at issue is considered investigational for treatment of the enrollees medical condition.  The physician reviewer found that in this case, Anser ADA was recommended to direct the management of the patients Crohns disease. The use of Anser ADA has not been clinically proven to improve patient clinical outcomes, and has not definitively demonstrated clinical utility. The effectiveness of Anser ADA compared with conventional courses of action remains unproven. Patients being treated with adalimumab may experience loss of response, but the appropriate method for determination of the cause for loss of response is not clear. The published studies on the use of anti-adalimumab antibodies and serum levels are retrospective and/or observational in nature (Karmiris, et al; Imaeda, et al). The study by Karmiris and colleagues found no direct relationship between trough serum adalimumab concentration or anti-adalimumab antibody and short-term treatment efficacy. In addition, prospective controlled trials providing evidence for the effectiveness of anti-adalimumab antibody testing and serum level testing as part of a clinical management strategy are lacking. Therefore, the medical literature does not support Anser ADA as likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. Based upon the information set forth above, the testing at issue was not likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. The Health Insurers denial should be upheld.
Appeal type: Experimental
Decision: Upheld

Summary Reviewer 3
A 60-year-old female enrollee has requested reimbursement for DecisionDx-Melanoma testing performed on 4/15/19. The Health Insurer has denied this request and reported that the services at issue were investigational for the evaluation of the enrolleeas melanoma. The physician reviewer found that Melanoma is a cancer that is curable in its earliest stages. Cutaneous melanoma is initially treated by wide surgical excision and sampling of sentinel lymph nodes for those with high depth of invasion, 0.76-1.0 mm. Metastases to regional lymph nodes may be amenable to excision, but this suggests a high risk for the development of metastatic disease in the future. Such patients may be observed or treated with interferon-alpha. The data on DecisionDx-Melanoma testing has not made it part of routine analysis after sentinel lymph node biopsy. There has also been some lack of consistency between various genes being used as biomarkers. The test is novel, and it is unclear how best to incorporate it into the treatment algorithm beyond standard staging techniques. Thus, DecisionDx-Melanoma testing performed on 4/15/19 was not likely to have been more beneficial than other methods of evaluating this patient.
Appeal type: Experimental
Decision: Upheld

Summary Reviewer 2


A 54-year-old female enrollee has requested reimbursement for Anser IFX measurement of serum infliximab (IFX) provided on 11/30/15. The Health Plan has denied this request indicating that the service at issue was considered investigational for evaluation the enrollees ulcerative colitis.The physician reviewer found the Prometheus Anser IFX test is a quantitative measurement of serum infliximab (IFX) and anti-IFX antibodies. Some evidence exists that low serum levels of infliximab or adalimumab and/or the presence of antibodies to infliximab or adalimumab may play a role in primary or secondary response failures. However, there are few well controlled clinical trials to confirm that use of the Anser testing leads to improved patient outcomes or quality of life as opposed to the standard method of treatment (Steenholdt, et al; Nanda, et al). As such, the clinical utility of measuring drug antibody concentrations has not been established, and it has not been established how patient management would change based on test results. Moreover, it has not yet been established whether the use of threshold levels aid in the discrimination of treatment response, or has the optimal timing of when to measure antibody levels been established. In this case, the patients failure to tolerate 6-mercaptopurine may have proved etiologic, rather than a failure of Remicade, in exacerbating proctitis. Thus, the Anser IFX measurement of serum infliximab (IFX) provided on 11/30/15 was not likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. Based upon the information set forth above, the testing at issue was not likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. The Health Insurers denial should be upheld.
Appeal type: Experimental
Decision: Upheld

Summary Reviewer 1 
 
A 63-year-old female enrollee has requested reimbursement for Guardant360 testing performed 
on 2/04/21. The Health Insurer has denied this request and reported that the services at issue 
were  investigational  for  the  evaluation  of  the  enrollees  medical  condition.  The  physician 
reviewer found that the National Comprehensive Cancer Network guidelines recommend biopsy 
of recurrence of disease. This patient has not been confirmed to have recurrent disease, just 
suspected.  Comprehensive  somatic  profiling  is  typically  reserved  for  confirmed  disease 
recurrence. It is not used to monitor for disease recurrence. Should she have confirmed disease 
recurrence, then several prior lines of therapy would be available prior to turning to therapies 
that may be revealed in targeted testing. Therefore, Guardant360 testing performed on 2/04/21 
was not likely to have been more beneficial than any available standard therapy.
Appeal type: Experimental
Decision: Overturned

Summary Reviewer 3


A 53-year-old female enrollee has requested reimbursement for the bilateral three dimensional digital breast tomosynthesis provided on 10/16/15. The Health Insurer has denied this request indicating that the services at issue are considered investigational for evaluation of the enrollees risk for breast cancer.  The physician reviewer found that there is currently a lack of peer-reviewed literature that supports the use of three dimensional breast tomosynthesis compared to available techniques, especially in a patient without an increased risk of breast cancer. Although breast tomosynthesis may be a promising technique, its clinical efficacy is yet to be substantiated in randomized clinical trials. All told, the digital breast tomosynthesis on 10/16/15 was not likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy.  Based upon the information set forth above, the services at issue were not likely to be more beneficial for evaluation of the patients medical condition than any available standard therapy. The Health Insurers denial should be upheld.