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Provenge® (sipuleucel-T)

Policy Number: MP-662

Effective Date: September 24, 2016

 Latest Review Date: May 2018

Category:   Medical           

Description of Procedure or Service:

Provenge® (sipuleucel-T) is part of a class of therapeutic agent used in the treatment of asymptomatic or minimally symptomatic, androgen-independent, metastatic prostate cancer. The agent comprises specially treated dendritic cells obtained from the patient through leukapheresis. The cells are then exposed in vitro to proteins that contain prostate antigens and immunologic stimulating factors, and then reinfused back into the patient.  At reinfusion, the cells are administered as three intravenous infusions given approximately two weeks apart. The proposed mechanism of action is that the treatment stimulates the patient’s own immune system to resist spread of the cancer.

Prostate cancer is the second leading cause of cancer-related deaths among American men, with an estimated incidence of 164,690 cases and an estimated number of 29,430 deaths in 2018. In most cases, prostate cancer is diagnosed at a localized stage and is treated with prostatectomy or radiotherapy. However, some patients are diagnosed with metastatic disease or recurrent disease after treatment of localized disease. Androgen ablation is the standard treatment for metastatic or recurrent disease. However, most patients who survive long enough eventually develop androgen-independent prostate cancer. At this stage of metastatic disease, docetaxel, a chemotherapeutic agent, has been demonstrated to confer a survival benefit of 1.9 to 2.4 months in randomized clinical trials. Chemotherapy with docetaxel causes adverse effects in large proportions of patients, including alopecia, fatigue, neutropenia, neuropathy, and other symptoms. Trials evaluating docetaxel included both asymptomatic and symptomatic patients, and results suggested a survival benefit for both groups. Because of the burden of treatment and its adverse effects, most patients therefore defer docetaxel treatment until cancer recurrence is symptomatic.

Cancer immunotherapy has been investigated as a treatment which could potentially be instituted at the point of detection of androgen-independent metastatic disease before significant symptomatic manifestations have occurred. The quantity of cancer cells in the patient during this time interval is thought to be relatively low, and it is thought that an effective immune response against the cancer during this time period could effectively delay or prevent progression. Such a delay could allow a course of effective chemotherapy, such as docetaxel, to be deferred or delayed until necessary, thus providing an overall survival benefit.

In 2010, the U.S. Food and Drug Administration (FDA) approved sipuleucel-T as an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC). CRPC (also known as androgen-independent prostate cancer [AIPC] or hormone-resistant [or recurrent or refractory] prostate cancer [HRPC]) is a form of prostate cancer that is resistant to standard hormone treatment, and is further defined as follows:

Disease progression evidenced by a progressively rising prostate specific antigen (PSA) (defined as a PSA rise by 2 ng/ml or more above the nadir PSA) or an increase in tumor mass on bone scan, X-ray, computerized tomography (CT) scan or magnetic resonance image (MRI) despite a castrate level of testosterone less than 20 ng/dl.

The precise mechanism of action for sipuleucel-T is unknown. The agent is designed to direct an immune response by targeting against prostatic acid phosphatase (PAP), an antigen expressed in most prostate cancers. Autologous peripheral blood mononuclear cells, including antigen presenting cells (APCs) collected by leukapheresis are activated during culture with PAP and granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune cell activator. The final product contains a minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF as well as T cells, B cells, natural killers (NK) cells and other cells. Sipuleucel-T is indicated for autologous use.

 

Policy:

Effective for dates of service on or after September 24, 2016

Provenge (sipuleucel-T) may be considered medically necessary for the treatment of individuals with metastatic castrate-resistant prostate cancer (CRPC) or hormone refractory prostate cancer (HRPC) for a single course of treatment (three infusions) who meet ALL of the following criteria:

  • Asymptomatic or minimally symptomatic; AND

  • ECOG (Eastern Cooperative Oncology Group) performance status 0-1; AND

  • No visceral (liver, lung, or brain) metastases; AND

  • Life expectancy of greater than six months; AND

  • Serum testosterone level less than 50 ng/dl (17 nmol/l); AND

  • No treatment within the previous 28 days with systemic glucocorticoids, external-beam radiation (EBRT), surgery, or systemic therapy for prostate cancer (except medical or surgical castration); AND

  • No chemotherapy within the previous 3 months; AND

  • No pathologic long bone fracture, or spinal cord compression within the last 3 months; AND

  • Progressive disease documented by either of the following:

    • Serum prostate-specific antigen (PSA) level of greater than or equal to 5 ng/ml and evidence of progressively increasing PSA values; OR

    • Osseous metastases on imaging with objective evidence of progression regardless of PSA levels.

Provenge (sipuleucel-T) for the treatment of prostate cancer  is not medically necessary and is considered investigational for all other conditions, including when the above criteria are not met.

__________________________________________________________________

Effective for dates of service September 1, 2015 through September 23, 2016

Provenge (sipuleucel-T) may be considered medically necessary for the treatment of individuals with metastatic castrate-resistant prostate cancer (CRPC) or hormone refractory prostate cancer (HRPC) for a single course of treatment (three infusions) who meet ALL of the following criteria:

  • Asymptomatic or minimally symptomatic; AND

  • ECOG (Eastern Cooperative Oncology Group) performance status 0-1; AND

  • No visceral (liver, lung, or brain) metastases; AND

  • Life expectancy of greater than six months;

Provenge (sipuleucel-T) for the treatment of prostate cancer is not medically necessary and is considered investigational for all other conditions, including when the above criteria are not met.

 

Key Points:

Metastatic, Castration-Resistant Prostate Cancer

In 2016, Yi et al reported on a meta-analysis that identified 3 randomized controlled trials (RCTs) on sipuleucel-T for treating castration-resistant prostate cancer. A pooled analysis of the 3 RCTs found significantly improved overall survival (OS) with sipuleucel-T compared with placebo (hazard ratio [HR], 0.73, 95% confidence interval [CI], 0.61 to 0.88; I2=0%). There was no significant difference between sipuleucel-T and placebo in time to progression of prostate cancer (HR=0.88; 95% CI, 0.74 to 1.06; I2=4%). Rates of individual adverse events were pooled, and there were no significant differences between sipuleucel-T and placebo in any of the adverse events, which consisted of fatigue, back pain, headache, arthralgia, and constipation. Stroke rates were not reported.

Sipuleucel-T has been studied in 3 of double-blind, placebo-controlled randomized controlled trials (RCTs). These studies were published by Small et al (2006), Higano et al (2009), and Kantoff et al (2010), and were extensively presented in a briefing document available from the U.S. Food and Drug Administration (FDA). Patients enrolled in these trials all had castration-resistant metastatic prostate cancer, were asymptomatic or mildly symptomatic, in good physical health characterized by Eastern Cooperative Oncology Group (ECOG ) Performance Status 0 or 1, and had tumors with positive staining for prostatic acid phosphatase (PAP).

Table 1 describes the two early identically designed studies. Patients with asymptomatic metastatic prostate cancer were randomized to receive either sipuleucel-T or a control infusion of untreated dendritic cells. Principal outcome was time to disease progression, defined as the time from randomization to the first observation of disease progression. Disease progression could be defined as radiologic progression (based on several imaging criteria), clinical progression (based on prostate cancer-related clinical events, such as pathologic fracture), or pain progression (based on onset of pain corresponding to anatomic location of disease).

Studies were not designed to establish efficacy based on overall survival. On progression of cancer, patients were allowed to have additional treatment as needed including chemotherapy. Patients originally assigned to placebo were allowed to cross over by receiving their own dendritic cells pulsed with PA2024 antigen (recombinant fusion protein comprising human PAP linked to granulocyte-macrophage colony-stimulating factor), but prepared from frozen dendritic cells harvested from their initial leukapheresis procedures.

Table 1: Description of randomized Phase III Trials of Sipuleucel-T

Study Name

Design

Eligibility

Treatment

Outcomes

9901A 9902A

Randomized double-blind, placebo-controlled

Metastatic prostate cancer by imaging, asymptomatic and progressing by imaging or rising PSA

Exp: 3 infusions of vaccine

Ctl: 3 infusions of placebo dendritic cells

Primary: disease progression (radiologic, clinical, pain) Secondary: time to pain, time to progression

IMPACT

Randomized double-blind, placebo-controlled

Metastatic prostate cancer by imaging, asymptomatic or minimally symptomatic and progressing by imaging or rising PSA

Exp: 3 infusions of vaccine

Ctl: 3 infusions of placebo dendritic cells

Primary: overall survival Secondary: time to objective disease progression

Ctl: control arm; Exp: experimental arm; PSA: prostate-specific antigen

As shown in Table 2, results of study 9901A for the principal outcome of time to progression did not show a significant difference between vaccine and control. Median time to progression was 11.7 weeks for the vaccine group and 10.0 weeks for the control group.

Table 2: Results of Randomized, Phase III Trials of Sipuleucel-T

Study

Vaccine

Control

p

Study 9901A, n

82

45

Median time to progression, wk

11.7

10.0

0.052

Median time to clinical progression, wk

10.7

9.1

0.061

Overall median survival, mo

25.9

21.4

0.01

Overall survival at 36 mo, %

34

11

0.005 Multivariable adjusted, 0.002

Study 9902A, n

65

33

Median time to progression, wk

10.9

9.9

0.719

Overall median survival, mo

19.0

15.7

0.331

IMPACT study, n

341

171

Overall median survival, mo

25.8

21.7

0.032

Overall survival at 36 mo, %

31.7

23.0

0.036

Time to progression

Not reported

Not reported

HR=0.95, p=0.628

HR: hazard ratio.

A survival analysis of study 9901A was presented in the FDA briefing document, with caveats that the study was not powered to show a survival effect and that a primary method of survival analysis was not prespecified in the protocol. Using a log-rank test, median survival times were 25.9 months for vaccine-treated patients and 21.4 months for placebo-treated patients, a statistically significant difference (p=0.011). At 36 months, survival rate was 34% for vaccine-treated patients and 11% for placebo-treated patients.

The FDA briefing document shows analyses of possible confounders regarding the survival analysis. After disease progression, patients in both groups received chemotherapy, but the rate of chemotherapy was slightly higher in the placebo group (48% vs 36%, respectively). Examination of the causes of death did not reveal any obvious spurious elevation of noncancer deaths in the placebo group. The published version of study 9901A by Small et al (2006) analyzed the survival data after adjusting for prognostic factors and found a significant association of sipuleucel-T treatment and survival (hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.31 to 3.44).

Because study 9901A did not meet its principal outcome end point for efficacy, enrollment for its partner study 9902A was suspended. Its sample size was therefore smaller, and the study subsequently had lower statistical power. As shown in Table 1, results for study 9902A showed a median time to progression of 10.9 weeks in the vaccine group versus 9.9 weeks in the placebo group, which was not statistically significant. A survival analysis of study 9902A showed that median survival was 19 months in vaccine-treated patients and 15.7 months in control, which also was not statistically significant.

Higano et al (2009) pooled survival data from the two studies. Pooled analysis showed a 33% reduction in the risk of death (HR=1.50; 95% CI, 1.10 to 2.05; p=0.011). The association was robust to adjustments in imbalances in baseline prognostic factors and post progression chemotherapy use.

Because these earlier studies did not meet criteria for success for their principal end points, FDA did not approve sipuleucel-T in 2007. A larger Phase III trial of similar design called IMPACT enrolling 512 patients was designed with a principal end point of overall survival. Analyses used to support FDA approval reported a 22% reduction in overall mortality in patients treated with sipuleucel-T. Treatment extended median survival by 4.1 months, compared with placebo (25.8 months vs 21.7 months, respectively) and improved three-year survival by a relative 38%, compared with placebo (31.7% vs 23.0%, respectively). Results adjusted for subsequent docetaxel use and timing, as well as analyses examining prostate cancer-specific survival showed similar magnitude and statistical significance of the survival benefit. Of note, 14% of enrolled subjects in this trial had received prior docetaxel. In retrospective, prespecified, multivariate subgroup analysis, several baseline factors were associated with overall survival: prostate-specific antigen (PSA), lactate dehydrogenase, hemoglobin, ECOG Performance Status, alkaline phosphatase, and Gleason score. Analysis of PSA by quartiles showed that men in the lowest quartile had the greatest survival benefit with sipuleucel-T: 49% reduced mortality compared with 26% reduced mortality in the second quartile, 19% in the third quartile, and 16% in the highest quartile.

Small et al (2014) pooled data for time to disease-related pain and time to first use of opioid analgesics from all 3 RCTs. Median time to disease-related pain was 5.6 months for sipuleucel-T versus 5.3 months for control (HR=0.82; 95% CI, 0.62 to 1.09). Median time to first use of opioid analgesics was 12.6 months for sipuleucel-T versus 9.7 months for control (HR=0.76; 95% CI, 0.58 to 0.99).

Safety

Regarding the safety of sipuleucel-T, most adverse effects were Grade 1 and 2 and resolved within 48 hours. The rate of serious adverse events was not statistically different between vaccine- and placebo-treated patients. However, one difficulty in assessing potential adverse effects by comparing sipuleucel-T with placebo is that placebo comprised infusion of untreated dendritic cells, which may cause adverse effects. FDA reviewers expressed concern regarding a possible association of sipuleucel-T with cerebrovascular events, as eight (5%) of 147 vaccine-treated patients experienced cerebrovascular-related adverse events, compared with zero placebo-treated patients in the two early trials. In the latest available report of adverse effects reported in the full prescribing information, incidence of stroke was 3.5% in the sipuleucel-T group and 2.6% in the control group, but these figures appear to include data from trials evaluating a different indication. In the FDA review summarizing cerebrovascular event rates from studies 9901A, 9902A, and interim data from IMPACT, incidence of stroke was 4.9% (17/345) in sipuleucel-T-treated patients and 1.7% (3/172) in placebo-treated patients (p=0.092). FDA review called the cerebrovascular event rate a “potential safety signal” and included as part of the approval a postmarketing study, based on a registry design, to assess the risk of cerebrovascular events in 1500 patients with prostate cancer who receive sipuleucel-T.

Section Summary

For patients with metastatic, castration-resistant prostate cancer, three RCTs of sipuleucel-T have been published. The three RCTs are consistent in reporting an improvement in overall survival of approximately four months compared with placebo. Two trials also reported that 36-month survival was significantly improved for patients receiving sipuleucel-T, with absolute improvements in survival of 9% and 23%. Time to progression was slightly longer in the sipuleucel-T groups, but this difference was not statistically significant. A meta-analysis of the 3 RCTs found significantly improved OS, but not time to progression, with sipuleucel-T compared with placebo. Serious adverse events were not increased in the sipuleucel-T group. However, given data reported to FDA, there was a concern about a possible increase in stroke risk and this is being studied in an ongoing postmarketing study.

Nonmetastatic, Androgen-Dependent Prostate Cancer

In 2011, Beer et al published an RCT evaluating sipuleucel-T in the setting of nonmetastatic, androgen-dependent prostate cancer.13 Patients with prostate cancer detectable by PSA after radical prostatectomy received 3 to 4 months of androgen suppression therapy and were then randomized (2:1) to sipuleucel-T (n=117) or to control (n=59). The primary end point was time to biochemical failure. The median time to biochemical failure was 18.0 months for sipuleucel-T and 15.4 months for control. The difference between groups was not statistically significant (HR=0.936, p=0.737). The PSA doubling time after testosterone recovery was 155 days in the sipuleucel-T group and 105 days in the placebo group (p=0.038). At the data cutoff point, 16% developed distant failure. The risk of distant failure did not significantly favor the sipuleucel-T group (p=0.021); however, the authors noted that this analysis had limited power.

Section Summary

A single RCT has been performed in patients with nonmetastatic, androgen dependent prostate cancer. This trial did not show any benefit for sipuleucel-T compared with control. Therefore, evidence on treatment of nonmetastatic prostate cancer is not sufficient to determine that health outcomes are improved.

Summary

For individuals who have metastatic, castration-resistant prostate cancer who receive sipuleucel-T (Provenge), the evidence includes 3 randomized controlled trials (RCTs) and a systematic review of these RCTs.  Relevant outcomes are: overall survival, disease-specific survival, change in disease status, and treatment-related morbidity. The 2 earlier RCTs of sipuleucel-T were not specifically designed to demonstrate a difference in overall mortality but did show a survival difference. The third RCT, which was designed to demonstrate a mortality difference, showed a similar improvement in overall survival. All 3 studies were consistent in demonstrating that sipuleucel-T does not delay time to measureable progression of disease. A meta-analysis of the 3 RCTs found significantly improved overall survival, but not time to progression, with sipuleucel-T compared with placebo. Serious adverse events were not increased in the sipuleucel-T group. However, the available data suggested, but did not confirm, an increase in stroke risk; this is being evaluated in a postmarketing study. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have nonmetastatic, castration-resistant prostate cancer who receive sipuleucel-T (Provenge), the evidence includes a RCT. Relevant outcomes are: overall survival, disease-specific survival, change in disease status, and treatment-related morbidity The RCT did not find a statistically significant difference between sipuleucel-T and control in time to biochemical failure. The RCT was not designed to evaluate the impact of sipuleucel-T on mortality. The evidence is insufficient to determine the effects of the technology on health outcomes.

 

Key Words:

Provenge, Sipuleucel-T therapy, Cellular immunotherapy, prostate cancer

 

Approved By Governing Bodies

On April 29, 2010, the U.S. Food and Drug Administration (FDA) approved Provenge® (sipuleucel-T, Dendreon Corp, now Sanpower, Jiangsu, China) via a Biologics Licensing Application (BLA) for "the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer (for autologous use only).” Approval was contingent on agreement of the manufacturer to conduct a postmarketing study, based on a registry design, to assess the risk of cerebrovascular events in 1,500 patients with prostate cancer who receive sipuleucel-T.

 

Benefit Application:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.  

 

Current Coding: 

HCPCS codes:

                              Q2043        Sipuleucel-T, minimum of 50 million autologous CD54+ cells activated

                                                  with PAP-GM-CSF, including leukapheresis and all other preparatory

                                                  procedures, per infusion

 

References:

  1. Basch E, Loblaw DA, Oliver TK, et al. Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol. Oct 20 2014; 32(30):3436-3448.

  2. Beer TM, Bernstein GT, Coman JM et al.  Randomized Trial of Autologous Cellular Immunotherapy with Sipuleucel-T in Androgen-Dependent Prostate Cancer.  Clin Cancer Res 2011; 17(13):4558-4567. 

  3. Berry DL, Moinpour CM, Jiang CS, et al.  Quality of life and pain in advanced stage prostate cancer: Results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone.  J Clin Oncol 2006; 24(18):2828-35.

  4. Dendreon Corporation.  Provenge® (sipuleucel-T) prescribing information. Seattle, WA; April 2010.  Available online at www.provenge.com/pdf/prescribing-information.pdf.

  5. Fitzpatrick JM, Bellmunt J, Fizazi K et al. Optimal management of metastatic castration-resistant prostate cancer: Highlights from a European Expert Consensus Panel. Eur J Cancer 2014; 50(9):1617-27.

  6. Higano CS, Schellhammer PF, Small EJ, et al.  Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer.  Cancer 2009; 115(16):3670-9.

  7. Kantoff PW, Higano CS, Shore ND et al. Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer. N Engl J Med 2010; 363(5):411-22.

  8. Mohler JL, Armstrong AJ, Bahnson RR et al. Prostate cancer, version 3.2012: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2012; 10(9):1081-7.

  9. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: prostate cancer, version 2.2017. Available online at: www.nccn.org/professionals/physician_gls/PDF/prostate.pdf.

  10. National Cancer Institute (NCI). Surveillance, Epidemiology, and End Results (SEER). SEER Stat Fact Sheets: Prostate Cancer. www.seer.cancer.gov/statfacts/html/prost.html.

  11. Schellhammer PF, Chodak G, Whitmore JB et al. Lower Baseline Prostate-specific Antigen Is Associated With a Greater Overall Survival Benefit From Sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) Trial. Urology 2013; 81(6):1297-302.

  12. Southwest Oncology G, Berry DL, Moinpour CM, et al. Quality of life and pain in advanced stage prostate cancer: results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone. J Clin Oncol. Jun 20 2006; 24(18):2828-2835.

  13. Small EJ, Schellhammer PF, Higano CS, et al.  Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer.  J Clin Oncol 2006; 24(19):3089-94.

  14. Small EJ, Higano CS, Kantoff PW, et al. Time to disease-related pain and first opioid use in patients with metastatic castration-resistant prostate cancer treated with sipuleucel-T. Prostate Cancer Prostatic Dis. Sep 2014; 17(3):259-264.

  15. Tannock IF, de Wit R, Berry WR, et al.  Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.  N Engl J Med 2004; 351(15):1502-12.

  16. U.S. Food and Drug Administration. Cellular, Tissue and Gene Therapies Advisory Committee Meeting, Clinical Briefing Document: Provenge® (sipuleucel T), 03/29/2007. Available online at: www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4291B1_2a.pdf.

  17. U.S. Food and Drug Administration (FDA). April 29, 2010 Approval Letter – Provenge 2010; www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/Approved/ucm210215.htm.

  18. Yi R, Chen B, Duan P, et al. Sipuleucel-T and androgen receptor-directed therapy for castration-resistant prostate cancer: a meta-analysis. J Immunol Res. 2016; 2016:4543861.

 

Policy History:

Medical Policy Group, policy transferred to pharmacy with effective date September 1, 2015

Medical Policy Group, August 2016 (2): Updates to Description, Key Points, and References; policy statement updated to include criteria for serum testosterone level, documentation of disease progression, and prior treatment requirements. 

Medical Policy Group, July 2017 (2): Updates to Description, Key Points, Approved by Governing Bodies, and References; no change to policy statement.

Medical Policy Group, May 2018 (2): Updates to Description; no change in policy statement.


This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

 

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

 

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.