Name of Policy: Islet Transplantation

Transcription

1 Name of Policy: Islet Transplantation Policy #: 300 Latest Review Date: June 2014 Category: Surgery Policy Grade: B Background/Definitions: As a general rule, benefits are payable under Blue Cross and Blue Shield of Alabama 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. Page 1 of 11

2 Description of Procedure or Service: Pancreatectomy is utilized in the treatment of patients with chronic pancreatitis. Autologous islet transplantation, performed in conjunction with pancreatectomy, is proposed to reduce the likelihood of insulin-dependent diabetes. Moreover, allogeneic islet transplantation is being investigated as a treatment or cure for selected patients with Type I diabetes. In autologous islet transplantation, during the pancreatectomy procedure, islet cells are isolated from the resected pancreas using enzymes, and a suspension of the cells is injected into the portal vein of the patient s liver. Once implanted, the beta cells in these islets begin to make and release insulin. In the case of allogeneic islet cell transplantation, cells are harvested from the deceased donor s pancreas, processed, and injected into the recipients portal vein. Up to three donor pancreas transplants may be required to achieve insulin independence. Allogenic transplantation may be performed in the radiology department. Chronic Pancreatitis Primary risk factors for chronic pancreatitis include toxic-metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis, or obstructive (the TIGAR-O classification system). Patients with chronic pancreatitis may experience intractable pain that can only be relieved with a total or near total pancreatectomy. However, the pain relief must be balanced against the certainty that the patient will be rendered an insulin-dependent diabetic. Autologous islet transplantation has been investigated as a technique to prevent this serious morbidity. Type I Diabetes Allogeneic islet transplantation has been used for type1 diabetes to restore normoglycemia and, ultimately, reduce or eliminate the long-term complications of diabetes such as retinopathy, neuropathy, nephropathy, and cardiovascular disease. Islet transplantation potentially offers an alternative to whole-organ pancreas transplantation. However, a limitation of islet transplantation is that two or more donor organs are usually required for successful transplantation, although experimentation with single-donor transplantation is occurring. A pancreas that is rejected for whole-organ transplant is typically used for islet transplantation. Therefore, islet transplantation is recommended only for patients with frequent and severe metabolic complications who have consistently failed to achieve control with insulin-based management. In 2000, a modified immunosuppression regimen increased the success of allogeneic islet transplantation. This regimen was developed in Edmonton, Canada and is known as the Edmonton protocol. Policy: Autologous pancreas islet transplantation meets Blue Cross and Blue Shield of Alabama s medical criteria for coverage as an adjunct to a total or near total pancreatectomy in patients with chronic pancreatitis. Page 2 of 11

3 Allogeneic islet transplantation does not meet Blue Cross and Blue Shield of Alabama s medical criteria for coverage for the treatment of Type 1 diabetes and is considered investigational. Islet transplantation in all other situations does not meet Blue Cross and Blue Shield of Alabama s medical criteria for coverage and is considered investigational. Blue Cross and Blue Shield of Alabama 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. Blue Cross and Blue Shield of Alabama 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. Key Points: Chronic Pancreatitis In 2012, Bramis et al published a systematic review of studies on islet transplantation after total pancreatectomy in patients with chronic pancreatitis. The investigators searched for studies reporting on patients who had been treated with total, subtotal or completion pancreatectomy followed by islet autotransplantation. Case series were included if they included more than five patients and reported outcomes for consecutive patients. A total of 72 full-text articles were reviewed, and five studies were found to meet inclusion criteria. The postoperative insulin independence rate in the five studies ranged from 10% (mean follow-up, eight years) to 46% (mean follow-up, five years). In the study with the longest follow-up, the insulin independence rate was 28% at ten years. Two studies reported postoperative morphine use. In one study, patients reported a mean postoperative decrease in morphine use of 116 mg and in the other, a mean decrease of 55 mg of morphine was reported. An earlier systematic review of studies on islet transplantation after pancreatectomy was published in 2011 by Dong et al. Studies were included regardless of design or sample size. After reviewing 84 studies, 15 observational studies were found to meet eligibility criteria. There were 11 studies of total pancreatectomy, two studies of partial pancreatectomy, and two studies that included both types of surgery. Sample sizes in individual studies ranged from three to 173 patients. Thirteen studies included patients with chronic pancreatitis, and two included patients with benign pancreatic tumors. The pooled 30-day mortality was 5% (95% confidence interval [CI], 2% to 10%), and the cumulative mortality at one year (reported by ten studies) was 4.9% (95% CI, 2.6% to 7.3%) In a pooled analysis of data from 14 studies, the rate of insulin dependence at last follow-up was 4.6 per 100 person years (95% CI, 1.53 to 7.62). The pooled rate of insulin independence at one year (five studies) was 27% (95% CI, 21% to 33%) and at two years (three studies) was 21% (95% CI, 16% to 27%). Page 3 of 11

4 Representative studies included in the systematic reviews or published more recently are described next: A large single center series was reported by Sutherland et al in The study included 409 patients with chronic pancreatitis who underwent total pancreatectomy and islet transplantation between February 1977 and September Fifty-three of the 409 patients (13%) were children between the ages of five and 18 years. Actuarial survival postsurgery was 96% in adults and 98% in children after one year and 89% in adults and 98% in children after five years. A total of 15.9% of patients experienced surgical complications requiring reoperation during the initial admission. The most common reason for reoperation was bleeding, occurring in 9.5% of patients. At three years, 30% of patients were insulin independent (25% of adults and 55% of children). A survey of quality-of-life outcomes was initiated in October 2008; responses were available for 102 patients. At baseline, all 102 patients reported using narcotics for pain. At 12 months, the proportion of patients on narcotics decreased to 56% (n=32), and at 24 months, 41% of respondents (n=21) reported using narcotics. A 2014 study by Chinnakotla et al included 484 patients with chronic pancreatitis. Patients underwent total pancreatectomy and immediate islet auto transplantation. Using a Kaplan- Meier analysis method, ten-year survival was 84%. Patient survival at five years was 90.3% in the 80 patients with hereditary/genetic pancreatitis and 89.7% in the 404 patients with nonhereditary pancreatitis; the difference between groups was not statistically significant. Pancreatitis pain decreased significantly after the procedures, and there was no statistically significant difference in the rate of pancreatitis pain between the groups with and without genetic/hereditary disease. In 2008, Webb et al reported on 46 patients who had total pancreatectomy with immediate islet auto transplantation. Twelve had periods of insulin independence for a median of 16.5 months (range, 2 63 months), and five remain insulin independent. Insulin requirements increased over the ten-year follow-up, as have HgA1c levels; however, all patients tested were C-peptide positive at their most recent assessment, and high fasting and stimulated C-peptide positive values recorded at ten years after transplantation suggest significant graft function in the long term. Type 1 Diabetes In April 2004, TEC completed an evidence report on islet cell transplantation in type 1 diabetes in its capacity as an Evidence-based Practice Center for the Agency for Healthcare Research and Quality. The evidence report found that published data on clinical outcomes of islet-alone transplantation were limited by small patient numbers; few transplant centers, short duration of follow-up, and lack of standardized methods of reporting clinical outcomes. Rare, serious adverse events have occurred in patients given islet transplants; recent procedure modifications reportedly minimize risks of these adverse events. No procedure-related deaths, cytomegalovirus infection, or post-transplantation lymphoproliferative disease have been reported for islet-alone transplantation. The 2008 report from the Collaborative Islet Transplant Registry (CITR), which collects and monitors data on allogeneic islet transplantation in North America, Europe, and Australia, had Page 4 of 11

5 325 adult recipients in their registry as of April Three years after first infusion, 23% of islet-alone recipients were insulin independent (defined as insulin independent two or more weeks), 29% were insulin dependent with detectable C-peptide, 26% had lost function, and 22% had missing data. Seventy percent achieved insulin independence at least once, 71% of whom were still insulin independent 1 year later and 52% at two years. Factors that favored primary outcomes were higher number of islet infusions, greater number of total islet equivalents infused, lower pretransplant HbA1c levels, processing centers related to the transplant center, and larger islet size. The CITR published an updated report in 2012; the focus of the article was changes in outcomes over time. The number of patients receiving islet transplants was 214 during , 255 between mid and 208 from A total of 575 of the 677 (85%) islet transplant recipients received islets only; the remainder underwent simultaneous kidney and islet transplants. In the group, rates of insulin independence were 51% after one year, 36% after two years, and 27% after three years. Rates for the group were 66%, 55% and 44%, respectively. The incidence of clinically reportable adverse events in the first year after infusion decreased from 50% to 53% in to 38% in The rates of peritoneal hemorrhage or gallbladder infusion were 5.4% in and 3.1% in The authors did not report findings separately for the subset of patients who underwent islet-only transplants. In 2011, Thompson et al in Canada published findings from a prospective crossover study of intensive medical therapy (pretransplant) versus islet cell transplantation in patients with Type 1 diabetes. The article reported on 45 patients; at the time of data analysis, 32 had received islet cell transplants. Median follow-up was 47 months pretransplant and 66 months post-transplant. The overall mean HbA1c was 7.8% pretransplant and 6.7% post-transplant; this difference was statistically significant, p< In the 16 patients for whom sufficient data pre- and posttransplant were available on renal outcomes, the median decline in glomerular filtration rate (ml/min/month) was -6.7 pretransplant and -1.3 post-transplant (p=0.01). Retinopathy was assessed using the International Scale, which categorizes nonproliferative diabetic retinopathy as mild, moderate, or severe. Retinopathy progressed in 10 of 82 (12%) eyes pretransplant versus 0 of 51 post-transplant (p<0.01). (The numbers of patients in the retinopathy analyses were not reported). The rate of change in nerve conduction velocity did not differ significantly between groups (exact numbers not reported). The authors noted that their finding of reduced microvascular complications after islet transplantation may be due, in part, to their choice of maintenance immunosuppression. The study used a combination of tacrolimus and mycophenolate mofetil. Several case series have also been published. These series tend to have small sample sizes and relatively short-term follow-up. Representative series are described next. In 2013, Rickels et al reported on 12 patients with Type 1 diabetes and severe hypoglycemia who had islet transplantation. Mean glycosylated hemoglobin decreased from 7.0% ± 0.3% before the procedure to 5.6% ± 0.1% after six to seven months, p<0.01. All of the insulin sensitivity measures were significantly less than normal before islet transplantation and not significantly different from normal after transplantation. Adverse events were not discussed. Page 5 of 11

6 In 2013, O Connell et al reported on 17 patients with Type 1 diabetes and severe hypoglycemia who underwent islet transplantation in Australia. The primary end point was the proportion of patients who had had an HbA1c less than 7% and no severe hypoglycemic events two months after the initial transplant. (Patients could have one or two infusions.) Fourteen of the 17 (82%) patients achieved the primary end point. Nine (53%) patients attained insulin independence for a median of 26 months. At the time of data analysis for this publication, six patients remained insulin independent. Most adverse events related to immunosuppression. Seven of the 17 (41%) patients developed mild lymphopenia and one developed Clostridium difficile colitis; these all responded to treatment. Eight patients developed anemia shortly after transplant and one required a blood transfusion. Procedure-related complications included one partial portal vein thrombosis and three postoperative bleeds; two of the bleeds required transfusion. Patients were followed for different amounts of time; long-term follow-up data were not available for a consistent length of time. In 2012, Vantyghem et al reported on 23 patients with Type 1 diabetes who underwent islet transplantation; 14 had islet-only transplants, and nine had islet after kidney transplants. Median HbA1c was 8.3% at baseline and 6.7% at three years. Ten of the 23 patients (43%) were insulin independent three years after islet transplantation. Findings were not reported separately for the islet-only transplant recipients. Recent papers have highlighted research in the areas of islet cell regenerative therapy including stem-cell technology, encapsulating islets to protect them from the host immune system by a semipermeable capsule, transplantation site, and xenotransplantation. In addition, novel immunosuppressive regimens using biologics have been discussed. Summary Autologous islet transplantation is proposed in conjunction with pancreatectomy for patients with chronic pancreatitis. Although the published experience with autologous islet cell transplantation is limited, the procedure appears to significantly decrease the incidence of diabetes after total or near total pancreatectomy in patients with chronic pancreatitis. In addition, this procedure is not associated with serious complications itself and is performed as an adjunct to the pancreatectomy procedure. Thus, this may be considered medically necessary. The techniques for allogeneic islet cell transplants are evolving, and the impact on the net health outcome is still uncertain. Moreover, longer follow-up with larger numbers of patients is needed before conclusions can be drawn about the safety of allogeneic islet transplantation and its impact on diabetes mellitus and associated complications. Thus, this technology is considered investigational for patients with diabetes Type 1. Practice Guidelines, and Position Statements NICE guidance published in 2008 states that the evidence on allogeneic pancreatic islet cell transplantation for Type 1 diabetes mellitus shows short-term efficacy with some evidence of long term efficacy evidence on safety shows that serious complications may occur and the longterm immunosuppression required is also associated with risk of adverse events. The procedure is particularly indicated for patients with hypoglycemia unawareness or those already on immunosuppressive therapy because of renal transplantation. A 2008 update of guidance on autologous islet cell transplantation for improved glycemic control after pancreatectomy states Page 6 of 11

7 that studies show some short-term efficacy, although most patients require insulin therapy in the long term. Complications result mainly from the major surgery involved in pancreatectomy rather than from the islet cell transplantation. Key Words: Allogeneic islet cell transplantation, islet cell transplantation, pancreas, autologous islet cell transplantation Approved by Governing Bodies: Islet cells are subject to regulation by the U.S. Food and Drug Administration (FDA), which classifies allogeneic islet cell transplantation as somatic cell therapy, requiring premarket approval. Islet cells also meet the definition of a drug under the federal Food, Drug, and Cosmetic Act. Clinical studies to determine safety and effectiveness outcomes of allogeneic islet transplantation must be conducted under FDA investigational new drug (IND) regulation. While at least 35 IND applications have been submitted to the FDA, no center has yet to submit a biologics license application. 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 contracts: 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: CPT Codes: Pancreatectomy, total or subtotal, with autologous transplantation of pancreas or pancreatic islet cells Unlisted procedure, pancreas (Effective for dates of service on or after January 1, 2012) HCPCS: G0341 Percutaneous islet cell transplant, includes portal vein catheterization and infusion G0342 Laparoscopy for islet cell transplant, includes portal vein catheterization and infusion G0343 Laparotomy for islet cell transplant, includes portal vein catheterization and infusion S2102 Transplant, islet cell tissue, allogeneic Page 7 of 11

8 Previous Coding: 0141T 0142T 0143T Pancreatic islet cell transplantation through portal vein, percutaneous (Deleted effective January 1, 2012) Pancreatic islet cell transplantation through portal vein, open (Deleted effective January 1, 2012) Laparoscopy, surgical, pancreatic islet cell transplantation through portal vein (Deleted effective January 1, 2012) References: 1. Aguayo-Mazzucato C, bonner-weir S. Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol 2010;6(3): Alejandro R, Barton FB, Hering BJ et al update from the Collaborative Islet Transplant Registry. Transplantation 2008;86(12): Badet L, Benhamou PY, et al. Expectations and strategies regarding islet transplantation: Metabolic data from the GRAGIL 2 trial. Transplantation, July 2007; 84(1): Barton FB, Rickels MR, Alejandro R et al. Improvement in outcomes of clinical islet transplantation: Diabetes Care 2012; 35(7): Blue Cross Blue Shield Association. Islet transplantation. Medical Policy Reference Manual, February Bramis K, Gordon-Weeks AN, Friend PJ et al. Systematic review of total pancreatectomy and islet autotransplantation for chronic pancreatitis. Br J Surg 2012; 99(6): Chinnakotla S, Radosevich DM, Dunn TB et al. Long-term outcomes of total pancreatectomy and islet auto transplantation for hereditary/genetic pancreatitis. J Am Coll Surg 2014; 218(4): Close N, Alejandro R, Hering B, et al. Second annual analysis of the collaborative islet transplant registry. Transplant Proc, January-February 2007; 39(1): Collaborative Islet Transplant Registry (CITR) Annual Report. CITR Coordinating Center. The EMMES Corporation, Rockville, MD. July 1, spitfire.emmes.com/study/isl/reports/citr%20annual%20report%201%20july% %20CD.pdf. 10. Cure P, Pileggi A, Froud T et al. Improved metabolic control and quality of life in seven patients with type 1 diabetes following islet after kidney transplantation. Transplantation 2008;85(6): De Vos P, Spasojevic M, Faas MM. Treatment of diabetes with encapsulated islet. Adv Exp Med Biol 2010;670: Dong M, Parsaik AK, Erwin PJ et al. Systematic review and meta-analysis: islet autotransplantation after pancreatectomy for minimizing diabetes. Clin Endocrinol (Oxf) 2011; 75(6): Esker B, Cooper DK. Overcoming the barriers to xenotransplantation: prospects for the future. Expert Rev Clin Immunol 2010;6(2): Fiorina P and Secchi A. Pancreatic islet cell transplant for treatment of diabetes. Endocrinol Metab Clin North America, December 2007; 36(4): Frank A, Deng S, Huang X, et al. Transplantation for type I diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets. Ann Surg 2004; 240(4): Page 8 of 11

9 16. Froud T, Ricordi C, Baidal DA, et al. Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience. Am J Transplant 2005; 5(8): Garcea G, Weaver J, Phillips J et al. Total pancreatectomy with and without islet cell transplantation for chronic pancreatitis: a series of 85 consecutive patients. Pancreas 2009;38(1): Leitato CB, Tharavanij T, Cure P et al. Restoration of hypoglycemia awareness after islet transplantation. Diabetes Care 2008;31(11): National Institute for Health and Clinical Excellence. Allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus Available online at Last accessed March, National Institute for Health and Clinical Excellence. Autologous pancreatic islet cell transplantation for improved glycemic control after pancreatectomy Available online at Last accessed March, O'Connell PJ, Holmes-Walker DJ, Goodman D et al. Multicenter Australian trial of islet transplantation: improving accessibility and outcomes. Am J Transplant 2013; 13(7): Piper MA, Seidenfeld J, Aronson N. Islet Transplantation in Type 1 Diabetes Mellitus. Evidence Report/Technology Assessment No. 98 (Prepared by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No ). AHRQ Publication No. 04-E Rockville, MD: Agency for Healthcare Research and Quality, April Posselt AM, Szot GL, Frassetto LA et al. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation 2010; 90(12): Rickels MR, Kong SM, Fuller C et al. Improvement in insulin sensitivity after human islet transplantation for type 1 diabetes. J Clin Endocrinol Metab 2013; 98(11):E Robertson RP, Lanz KJ, Sutherland DE, et al. Prevention of diabetes for up to 13 years by autoislet transplantation after pancreatectomy for chronic pancreatitis. Diabetes 2001; 50(1): Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med 2006; 355(13): Sponsored by University Hospital Grenoble. Trial Comparing Metabolic Efficiency of Islet Graft to Intensive Insulin Therapy for Type 1 Diabetes's Treatment (TRIMECO) (NCT ). Available online at: Last accessed March, Sponsored by University of British Columbia. A Comparison of Islet Cell Transplantation with Medical Therapy on the Risk of Progression of Diabetic Retinopathy and Diabetic Macular Edema (NCT ) Available online at: Last accessed April, Sponsored by Vancouver Coastal Health. A comparison of strict glucose control with usual care at the time of islet cell transplantation (NCT ). Available online at: Last accessed March, Sutherland DE, Gruessner AC, Carlson AM et al. Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes. Transplantation 2008;86(12): Page 9 of 11

10 31. Sutherland DE, Radosevich DM, Bellin MD et al. Total pancreatectomy and islet autotransplantation for chronic pancreatitis. J Am Coll Surg 2012; 214(4): Tan J, Yang S, Cai J et al. Simultaneous islet and kidney transplantation in seven patients with type 1 diabetes and end-stage renal disease using a glucocorticoid-free immunosuppressive regimen with alemtuzumab induction. Diabetes 2008;57(10): Thompson DM, Meloche M, Ao Z et al. Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation 2011; 91(3): van der Windt DJ, Bottino R, Kumar G et al. Clinical islet xenotransplantation: how close are we? Diabetes 2012; 61(12): Vantyghem MC, Raverdy V, Balavoine AS et al. Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (beta-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (beta-score greater than 3). J Clin Endocrinol Metab 2012; 97(11):E Wahoff DC, Papalois BE, Najarian JS, et al. Autologous islet transplantation to prevent diabetes after pancreatic resection. Ann Surg 1995; 222(4): Warnock Gl, Thompson DM, Meloche RM et al. A multi-year analysis of islet transplantation compared with intensive medical therapy on progression of complication in type 1 diabetes. Transplantation 2008; 86(12): Webb Ma, Illouz SC, Pollard CA et al. Islet auto transplantation following total pancreatectomy: a long-term assessment of graft function. Pancreas 2008;37(3): Policy History: Medical Policy Group, February 2007 (3) Medical Policy Administration Committee, February 2007 Available for comment March 1-April 14, 2007 Medical Policy Group, January 2009 (1) Medical Policy Panel, June 2010 Medical Policy Group, June 2010 (2) Medical Policy Group, June 2011 (1): Update to Description, Key Points and References Medical Policy Group, December 2011 (1): 2012 Coding Updates; deleted 0141T, 0142T, 0143T and replaced all with unlisted code Medical Policy Group, June 2012 (3): 2012 Updates Key Points & References Medical Policy Panel, June 2013 Medical Policy Group, June 2013 (3): 2013 Updates to Description, Key Points and References; no change in policy statement Medical Policy Group, October 2013 (3): Removed ICD-9 Procedure codes; no change to policy statement. Medical Policy Panel, May 2014 Medical Policy Group, June 2014 (3): 2014 Updates to Description, Key Points & References; added clarification to policy statement Islet transplantation in all other situations does not meet Blue Cross and Blue Shield of Alabama s medical criteria for coverage and is considered investigational no change in content Page 10 of 11

11 This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a caseby-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. Page 11 of 11