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Aetna Aetna
Clinical Policy Bulletin:
Infusion Pumps
Number: 0161
(Replaces CPB 110, CPB 338)

Policy

  1. Implantable Infusion Pumps

    Aetna considers implanted infusion pumps medically necessary durable medical equipment (DME) when all of the following criteria are met:

    • It is medically necessary that the drug be administered by an implanted infusion pump; and
    • The drug is medically necessary for the treatment of members (see medical necessity criteria for various types of infusion pumps below); and
    • The infusion pump has been approved by the FDA for infusion of the particular drug that is to be administered.

     

    1. Anti-spasmodic drugs

      Aetna considers an implantable infusion pump medically necessary when used to intrathecally administer anti-spasmodic drugs (e.g., baclofen) to treat chronic intractable spasticity in persons who have proven unresponsive to less invasive medical therapy as determined by the following criteria: 

      1. Member has failed a six-week trial of non-invasive methods of spasticity control, such as oral anti-spasmodic drugs, either because these methods fail to adequately control the spasticity or produce intolerable side effects; and
      2. Member has a favorable response to a trial intrathecal dosage of the anti-spasmodic drug prior to pump implantation. 

      Intrathecal baclofen (Lioresal) is considered medically necessary for the treatment of intractable spasticity caused by spinal cord disease, spinal cord injury, or multiple sclerosis and for stiff person syndrome.  Baclofen is considered medically necessary for persons who require spasticity to sustain upright posture, balance in locomotion, or increased function.

      Documentation in the member's medical record should indicate that the member's spasticity was unresponsive to other treatment methods and that the oral form of baclofen was ineffective in controlling spasticity or that the member could not tolerate the oral form of the drug.  A trial of oral baclofen is not a required prerequisite to intrathecal baclofen therapy in children ages 12 years old or less due to the increased risk of adverse effects from oral baclofen in this group.

      The medical record should document that the member showed a favorable response to the trial dosage of the baclofen before subsequent dosages are considered medically necessary.  An implanted pump for continuous fusion is considered not medically necessary for members who do not respond to a 100 mcg intrathecal bolus.

      Intrathecal baclofen is considered experimental and investigational as a treatment for neuromyotonia (Isaac's syndrome), hydrocephalus, and rheumatoid arthritis.

    2. Drugs for treatment of chronic intractable pain

      An implantable infusion pump is considered medically necessary when used to administer opioid drugs (e.g., morphine), ziconotide, and/or clonidine intrathecally or epidurally for treatment of severe chronic intractable pain of malignant or non-malignant origin in persons who have proven unresponsive to less invasive medical therapy as determined by the following criteria: 

      1. The member's history must indicate that he or she has not responded adequately to non-invasive methods of pain control, such as systemic opioids (including attempts to eliminate physical and behavioral abnormalities which may cause an exaggerated reaction to pain); and
      2. A preliminary trial of intraspinal opioid drug administration must be undertaken with a temporary intrathecal/epidural catheter to substantiate adequately acceptable pain relief, the degree of side effects (including effects on the activities of daily living), and acceptance. 

      Implantable infusion pumps for intrathecal or epidural infusion of opioids, ziconotide, and clonidine are considered experimental and investigational as a treatment for gastroparesis and for all other indications because their effectiveness for indications other than the one listed above has not been established. (Note: Currently, morphine and ziconotide are the only FDA-approved analgesics for long-term intrathecal infusion [Turk et al, 2011]).

    3. Intrahepatic chemotherapy infusion for liver metastases from colorectal cancer

      Implantable infusion pumps are considered medically necessary for administration of intrahepatic chemotherapy (e.g., floxuridine) to members with colorectal cancer and liver metastases.

      Aetna considers "one-shot" arterial chemotherapy for persons with liver metastases from colorectal cancer experimental and investigational.

      Note: An average 3 to 5 days inpatient hospitalization is medically necessary for intrahepatic chemotherapy. Hospital discharge is dependent on resolution of pain, nausea and vomiting which complicate the procedure. 

    4. Contraindications to implantable infusion pumps

      Implantable infusion pumps are considered not medically necessary for persons with the following contraindications to implantable infusion pumps: 

      1. Members who have an active infection that may increase the risk of the implantable infusion pump; or
      2. Members whose body size is insufficient to support the weight and bulk of the device; or
      3. Members with known allergy or hypersensitivity to the drug being used (e.g., oral baclofen, morphine, etc.); or
      4. Members with other implanted programmable devices where the crosstalk between devices may inadvertently change the prescription.

    5. Experimental and investigational uses of implanted infusion pumps

      Implanted infusion pumps are considered experimental and investigational for all other indications, including any of the following:

      1. Implantable infusion pumps for intrahepatic administration of chemotherapy for indications other than noted above, including treatment of primary hepatocellular carcinoma or hepatic metastases from cancers other than colorectal cancer; or
      2. Implantable pumps for the infusion of heparin for recurrent thromboembolic disease; or
      3. Implantable pumps for the infusion of insulin to treat diabetes; or
      4. Implantable pumps for the infusion of baclofen for chronic neuropathic pain (e.g., complex regional pain syndrome/reflex sympathetic dystrophy).

      See also CPB 0607 - Anesthetic Infusion Pumps.

  2. External Infusion Pumps

    Aetna considers external infusion pumps medically necessary DME for administration of any of the following medications:

    1. Certain parenteral anticancer chemotherapy drugs (e.g., cladribine, fluorouracil, cytarabine, bleomycin, floxuridine, doxorubicin, vincristine, vinblastine, cisplatin, paclitaxel) if the drug is part of an evidence-based chemotherapy regimen and parenteral infusion of the drug at a strictly controlled rate is necessary to avoid systemic toxicity or adverse effects, and the drug is administered either:(i) by continuous infusion over 8 hours; or(ii) by intermittent infusions lasting less than 8 hours that do not require the person to return to the physician's office prior to the beginning of each infusion; or
    2. Certain parenteral antifungal or antiviral drugs (e.g., acyclovir, foscarnet, amphotericin B, or ganciclovir); or
    3. Chemotherapy for primary hepatocellular carcinoma or colorectal cancer where the tumor is unresectable or the member refuses surgical excision of the tumor; or
    4. Deferoxamine for the treatment of acute iron poisoning and iron overload (only external infusion pumps are considered medically necessary); or
    5. Heparin for the treatment of thromboembolic disease and/or pulmonary embolism (only external infusion pumps used in an institutional setting are considered medically necessary); or
    6. Heparin to adequately anticoagulate women throughout pregnancy (warfarin compounds are not routinely used for this indication); or
    7. Insulin for persons with diabetes mellitus who meet the selection criteria for external insulin infusion pumps for diabetes set forth below; or
    8. Morphine or other narcotic analgesics (except meperidine) for intractable pain caused by cancer; or
    9. Other parenterally administered drugs where an infusion pump is necessary to safely administer the drug at home; or
    10. Parenteral epoprostenol or treprostinil for persons with pulmonary hypertension; or
    11. Parenteral inotropic therapy with dobutamine, milrinone, and/or dopamine.

    Aetna considers external infusion pumps experimental and investigational for all other indications.  See also CPB 0468 - Terbutaline Pump for Preterm Labor.

  3. External Insulin Infusion Pumps for Diabetes

    Aetna considers external insulin infusion pumps medically necessary DME for the persons with diabetes who meet the criteria in section A or in section B below:

    1. Members must meet all of the following criteria: 

      1. The member has been on a program of multiple daily injections of insulin (i.e., at least 3 injections per day), with frequent self-adjustments of insulin dose for at least 6 months prior to initiation of the insulin pump*; and 
      2. The member has completed a comprehensive diabetes education program; and
      3. The member has documented frequency of glucose self-testing an average of at least 4 times per day during the 2 months prior to initiation of the insulin pump**; and
      4. The member meets at least one of the following criteria while on multiple daily injections (more than 3 injections per day) of insulin: 

        1. Dawn phenomenon with fasting blood sugars frequently exceeding 200 mg/dL; or
        2. Elevated glycosylated hemoglobin level (HbA1c greater than 7.0%, where upper range of normal is less than 6.0%; for other HbA1c assays, 1% over upper range of normal); or
        3. History of recurring hypoglycemia (less than 60 mg/dL); or
        4. History of severe glycemic excursions; or
        5. Wide fluctuations in blood glucose before mealtime (e.g., pre-prandial blood glucose levels commonly exceed 140 mg/dL); or

      or

    2. The member has been on a pump prior to enrollment in Aetna, and has documented frequency of glucose self-testing an average of at least 4 times per day during the month prior to Aetna enrollment. 

      Aetna considers external infusion pumps for diabetes experimental and investigational where the above-listed criteria are not met.

      Footnote:

      * It may be considered medically necessary to initiate the use of insulin infusion pumps during pregnancy earlier than the criteria stated above to avoid fetal and maternal complications of diabetes and pregnancy. It may be considered medically necessary for poorly controlled women with diabetes to sometimes get started on the pump pre-pregnancy or in the first trimester. 

      Notes on external insulin infusion pumps

      • Aetna considers a disposable external insulin infusion pump (e.g., OmniPod Insulin Management System) an acceptable alternative to a standard insulin infusion pump for persons who meet medical necessity criteria for external insulin infusion pumps.
      • Aetna's medical necessity criteria for external infusion pumps for diabetes have been adapted from Medicare national policy on external insulin infusion pumps, as outlined in CMS's Coverage Issues Manual Section 60-14.
      • Documentation of continued medical necessity of the external insulin infusion pump requires that the member be seen and evaluated by the treating physician at least once every 6 months.
      • External subcutaneous insulin infusion pumps are only considered medically necessary for persons who have demonstrated ability and commitment to comply with a regimen of pump care, frequent self-monitoring of blood glucose, and careful attention to diet and exercise.
      • Some external insulin infusion pumps (e.g., Paradigm Real-Time Insulin Pump and Continuous Glucose Monitoring System, Animas OneTouch PING) are able to take results of the blood glucose reading, calculate the appropriate insulin infusion rate, wirelessly transmit the results from the blood glucose monitor to the pump, and automatically adjust the insulin infusion rate, saving the member some extra steps. These insulin pump features, when present, are considered integral to the external insulin infusion pump and blood glucose monitor.
      • The pump must be ordered by and follow-up care of the member must be managed by a physician with experience managing persons with insulin infusion pumps and who works closely with a team including nurses, diabetic educators, and dieticians who are knowledgeable in the use of insulin infusion pumps.

      See also CPB 0070 - Diabetes Tests, Programs and Supplies.

  4. Supplies and Drugs used with Implantable or External Infusion Pumps

    Aetna considers supplies that are needed for the effective use of the DME medically necessary. 

    Such supplies include those drugs and biologicals that must be put directly into the equipment in order to achieve the therapeutic benefit of the DME or to assure the proper functioning of the equipment.

  5. Replacement Pumps

    1. Replacement of a functioning insulin pump with an insulin pump with wireless communication to a glucose monitor is considered not medically necessary as such wireless communication has not been shown to improve clinical outcomes
    2. Replacement of an external insulin pump is considered medically necessary for children who require a larger insulin reservoir.
    3. The replacement of infusion pumps that are out of warranty, are malfunctioning, and cannot be refurbished is considered medically necessary.
  6. Transdermal Insulin Delivery Systems

    Aetna considers transdermal insulin delivery systems (e.g., V-Go™ disposable insulin delivery device) experimental and investigational becasue their effectiveness has not been established.



Background

Baclofen (Lioresal) is a derivative of gamma aminobutyric acid (GABA) that acts specifically at the spinal end of the upper motor neurons to cause muscle relaxation.  Intrathecal baclofen may be indicated for patients with severe chronic spasticity of spinal cord origin. An implantable infusion pump is required for the administration of intrathecal baclofen.  Intrathecal baclofen therapy is indicated for persons with severe chronic spasticity of spinal cord origin (including multiple sclerosis) that is refractory to oral baclofen or where there are unacceptable side effects from oral baclofen at the effective dose. The patient should be shown to respond to a single intrathecal bolus dose of up to 100 mcgs of baclofen. A positive response is defined as an average two-point drop on an objective muscle tone or spasm screening system (e.g., The Ashworth and Spasm scale). According to available guidelines, intrathecal baclofen therapy is not considered appropriate if the patient has a history of hypersensitivity to Lioresal, is pregnant or has inadequate birth control, has severely impaired renal function, has severe hepatic or gastrointestinal disease, or has cerebral lesions as the source of spasticity.

Brennan and Whittle (2008) stated that continuous infusion of intrathecal baclofen (ITB) via a subcutaneously implanted pump has developed over the past 2 decades as a powerful tool in the management of spasticity in various adult and pediatric neurological conditions. Acting more focally on spinal GABA receptors, ITB causes fewer systemic side effects than orally administered baclofen. The result is facilitation of daily caring, and symptomatic relief from painful spasm. With increasing experience of ITB use, novel applications and indications are emerging. These include the management of dystonia and chronic neuropathic pain. However, despite some recent authoritative reviews, there is still uncertainty about optimal use and evaluation of this therapy.

Shilt et al (2008) stated that ITB is an effective treatment of spasticity in patients with cerebral palsy (CP). However, several recent reports have raised concerns that the treatment may be associated with a rapid progression of scoliosis. The objective of this study was to further examine the effect of ITB treatment on the progression of scoliosis in patients with CP. Spastic CP patients who were ITB candidates were followed radiographically. Baseline Cobb angles of the primary curve were measured during the period of ITB pump insertion and at the most recent follow-up visit. Each patient was matched with a control patient by the diagnosis of CP, age, sex, topographical involvement, and initial Cobb angle. The mean rate of change in Cobb angle was compared between ITB and control patients using paired-t test. A multiple linear regression model was used to examine the difference, controlling for age, sex, topographical involvement, and initial Cobb angle. A total of 50 ITB patients and 50 controls were included in the analysis. There was no statistically significant difference between the mean change in Cobb angle in ITB patients (6.6 degrees per year) compared with the matched control patients (5.0 degrees per year, p = 0.39). The results from the multiple regression analysis also failed to show a statistically significant difference (0.92 degrees per year difference between ITB patients and controls, p = 0.56). The authors concluded that the progression of scoliosis in CP patients with ITB treatment is not significantly different from those without ITB treatment. The findings suggest that patients receiving ITB experience a natural progression of scoliosis similar to the natural history reported in the literature.

The discovery of spinal opiate receptors, and that the binding of morphine at relatively low concentrations to these receptors produced effective analgesia have led to the development of intraspinal analgesia for the management of pain.  This mode of opioid administration has become an attractive alternative for cancer patients whose pain is not relieved by conventional drugs and/or routes; and for others who cannot tolerate the side effects of systemic administration of opioids in the dose needed for adequate analgesia as the disease progresses.  A popular procedure for intraspinal administration of opioids analgesics is the implantation of an infusion pump which allows the direct delivery of opioids to the receptors in the spinal cord continuously and/or in an intermittent manner.

Available evidence indicates that chronic intrathecal opioids administration via implantable pumps can provide satisfactory pain relief for patients who suffer from intractable cancer pain.  In addition, it allows the patients to be less dependent on hospital services, thus improving the quality of their lives. Studies have also shown that the same method of treatment was successful in providing quality analgesia to carefully selected patients who experienced chronic pain from nononcologic origins, although reductions in pain and improvements in function is observed less consistently in noncancer pain. Some investigators have reported untoward side effects of intrathecal opioid administration, including development of a fibrous mass around the tip of the catheter, resulting in compression of the intrathecal space with displacement of the spinal cord.

To be considered for spinal analgesia, a patient must have a normal platelet count and no coagulation disorder, infection, or other problems that might preclude the use of spinal drugs.  Before the implantation of a permanent infusion system, an efficacy test is usually performed to assess the patient's response and dose.  One or several trial doses of 5 to 10 mg of epidural morphine, or 0.5 to 1.0 mg intrathecal morphine is/are administered while all other analgesic medications are stopped.  Subjective pain ratings and undesirable side effects are evaluated for several days.  A decision to implant the pump is made only if pain is markedly reduced and other opioid analgesics are not needed by the patient.

Aetna's medical necessity criteria for external infusion pumps for diabetes have been adapted from Medicare national policy on external insulin infusion pumps, as outlined in CMS's Coverage Issues Manual Section 60-14.

There is some limited evidence that external insulin infusion pumps improve glycemic control over multiple daily injections in persons with type 2 diabetes (Hammond, 2004; Pickup & Renard, 2008; Fatourechi, et al., 2009), although not all studies have been consistent (see, e.g., Raskin, et al., 2003; Herman, et al., 2005; Berthe, et al., 2007; Parkner, et al., 2008).

Fatourechi et al (2009) reported on a metaanalysis of randomized controlled clinical trials of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) in persons with diabetes.  The investigators identified 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study hemoglobin A1c (HbA1c) levels.  The investigators reported that patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, -0.2 %; 95 % confidence interval (CI): -0.3 to -0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95 % CI: 0.23 to 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95 % CI: 0.33 to 2.03).  Adolescents and adults with type 1 diabetes enrolled in cross-over trials had no-nsignificantly fewer minor hypoglycemia episodes per patient per week (-0.08; 95 % CI: -0.21 to 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95 % CI: 0.16 to 1.20; p (interaction) = 0.03).  The investigators reported that outcomes were not different in patients with type 2 diabetes.  The investigators concluded that "[c]ontemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia.  In type 2 diabetes, CSII and MDI had similar outcomes.  The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data."

Guidelines from the American Association of Clinical Endocrinologists (Robard, et al., 2007) provide a grade C recommendation for patients with type 2 diabetes, "[c]onsider use of continuous subcutaneous insulin infusion in insulin-treated patients." Guidelines from the National Institute for Health and Clinical Excellence (2008) do not recommend use of CSII in persons with type 2 diabetes.

An American Association of Clinial Endocrinologists (2010) consensus statement on insulin pumps in diabetes included a recommendation for use of insulin pumps in persons with type 2 diabetes. The consensus stated that the ideal continuous subcutaneous insulin infusion (CSII) candidate would be a patient with type 1 diabetes mellitus or absolutely insulin-deficient type 2 diabetes mellitus who currently performs 4 or more insulin injections and 4 or more self-monitored blood glucose measurements daily, is motivated to achieve tighter blood glucose control, and is willing and intellectually and physically able to undergo the rigors of insulin pump therapy initiation and maintenance. The consensus statement also included a recommendation for use of insulin infusion pumps in selected patients with insulin-requiring type 2 diabetes mellitus who satisfy any or all of the following: 1) C-peptide positive but with suboptimal control on a maximal program of basal/bolus injections; 2) substantial “dawn phenomenon”; 3) erratic lifestyle (eg, frequent long distance travel, shift-work, unpredictable schedules leading to difficulty maintaining timing of meals); 4) severe insulin resistance, candidate for U500 insulin by continuous subcutaneous insulin infusion (CSII). The consensus statement said that current literature on insulin pump use has focused primarily on the benefits of CSII in patients with type 1 diabetes mellitus, with some attention to the role of CSII in patients with severely insulin-deficient type 2 diabetes mellitus. The consensus statement indicated that "few clinical investigations have examined CSII use in patients with type 2 DM." The consensus statement noted that one analysis of 4 randomized controlled trials in patients with type 2 diabetes mellitus (citing Monami, et al.) found no significant HbA1c improvements and no significant differences in hypoglycemic risk with CSII versus multiple daily injection therapy over 12 weeks. The consensus statement noted, however, that there was a nonsignificant trend toward decreased insulin requirements was observed among CSII patients. The statement also cited other recent meta-analysis of insulin pump therapy in type 2 diabetes, one by Jeitler, et al. (2008) which they interpreted as finding "no conclusive CSII benefits for patients with type 2 DM", and a meta-analysis by Fatourechi, et al. (2009), which they interpreted as finding "CSII and MDI outcomes were similar among patients with type 2 DM." The consensus statement also referenced a nested case-control study of the use of insulin infusion pumps versus non-pump therapy in pregnant women with type 2 diabetes or gestational diabetes (Simmons, et al., 2001).

A systematic evidence review by Mukhopadhyay et al (2007) found no advantage of using continuous subcutaneous insulin infusion (CSII) over multiple daily injections in pregnant women with diabetes.  The investigators identified randomized controlled clinical trials of the effects of CSII versus multiple daily insulin injections on glycemic control and pregnancy outcome in women with diabetes.  Studies were rated for quality independently by 2 reviewers.  Summary weighted mean differences and odds ratios were estimated for insulin dose, birthweight, gestational age, mode of delivery, hypoglycemic/ketotic episodes, worsening retinopathy, neonatal hypoglycemia, and rates of intrauterine fetal death.  Six randomized clinical trials met the inclusion criteria.  The investigators found that pregnancy outcomes and glycemic control were not significantly different among treatment groups.  The investigators found higher numbers of ketoacidotic episodes and diabetic retinopathy in the CSII group, but these differences did not reach statistical significance.  The investigators found that this systematic review did not find any advantage or disadvantage of using CSII over multiple daily injections in pregnant diabetic women.

Cummins et al (2010) examined the clinical effectiveness and cost-effectiveness of using CSII to treat diabetes. These investigators updated the previous assessment report by reviewing evidence that has emerged since the last appraisal, and took account of developments in alternative therapies, in particular the long-acting analog insulins, which cause fewer problems with hypoglycaemia. The primary focus for type 1 diabetes mellitus (T1DM) was the comparison of CSII with MDI, based on the newer insulin analogs, but trials of neutral protamine Hagedorn (NPH)-based MDI that had been published since the last assessment were identified and described in brief. For type 2 diabetes mellitus (T2DM), all trials of MDI versus CSII were included, whether the long-acting insulin was analog or not, because there was no evidence that analog-based MDI was better than NPH-based MDI. Trials that were shorter than 12 weeks were excluded. Information on the patients' perspectives was obtained from 4 sources: (i) the submission from the pump users group -- Insulin Pump Therapy (INPUT); (ii) interviews with parents of young children who were members of INPUT; (iii) some recent studies; and (iv) from a summary of findings from the previous assessment report. Economic modeling used the Center for Outcomes Research (CORE) model, through an arrangement with the NICE and the pump manufacturers, whose submission also used the CORE model. The 74 studies used for analysis included 8 randomized controlled trials (RCTs) of CSII versus analog-based MDI in either T1DM or T2DM, 8 new (since the last NICE appraisal) RCTs of CSII versus NPH-based MDI in T1DM, 48 observational studies of CSII, 6 studies of CSII in pregnancy, and 4 systematic reviews. The following benefits of CSII were highlighted: better control of blood glucose levels, as reflected by HbA1c levels, with the size of improvement depending on the level before starting CSII; reduction in swings in blood glucose levels, and in problems due to the dawn phenomenon; fewer problems with hypoglycemic episodes; reduction in insulin dose per day, thereby partly off-setting the cost of CSII; improved quality of life, including a reduction in the chronic fear of severe hypoglycemia; more flexibility of lifestyle -- no need to eat at fixed intervals, more freedom of lifestyle and easier participation in social and physical activity; and benefits for the patients' family. The submission from INPUT emphasised the quality of life gains from CSII, as well as improved control and fewer hypoglycemic episodes. Also, there was a marked discrepancy between the improvement in social quality of life reported by successful pump users, and the lack of convincing health-related quality of life gains reported in the trials. With regard to economic evaluation, the main cost of CSII is for consumables, such as tubing and cannulae, and is about 1800 to 2000 pounds per year. The cost of the pump, assuming 4-year life, adds another 430 to 720 pounds per year. The extra cost compared with analog-based MDI averages 1700 pounds. Most studies, assuming a reduction in HbA1c level of 1.2 %, found CSII to be cost-effective. The authors concluded that based on the totality of evidence, using observational studies to supplement the limited data from RCTs against best MDI, CSII provides some advantages over MDI in T1DM for both children and adults. However, there was no evidence that CSII is better than analog-based MDI in T2DM or in pregnancy. They stated that further trials with larger numbers and longer durations comparing CSII and optimized MDI in adults, adolescents and children are needed. In addition, there should be a trial of CSII versus MDI with similar provision of structured education in both arms. A trial is also needed for pregnant women with pre-existing diabetes, to investigate using CSII to the best effect.

Transdermal insulin delivery has been advocated as a needle-free alternative to subcutaneous injection conventionally used to treat diabetes.  However, the effectiveness of transdermal insulin delivery in the management of diabetic patients has not been established.

Zu et al (2011) described the preparation and characterization of chitosan (CS)-polyvinyl alcohol (PVA) blend hydrogels for the controlled release of nano-insulin; CS- PVA blend hydrogels were prepared using glutaraldehyde as the cross-linking agent.  The obtained hydrogels, which have the advantages of both PVA and CS, can be used as a material for the transdermal drug delivery (TDD) of insulin.  The nano-insulin-loaded hydrogels were prepared under the following conditions: 1.2g of polyethylene glycol, 1.5 g of CS, 1.2 g of PVA, 1.2 ml of 1 % glutaraldehyde solution, 16 ml of water, and 40 mg of nano-insulin with 12 mins of mixing time and 3 mins of cross-linking time. The nano-insulin-loaded hydrogels were characterized using scanning electron microscopy, energy dispersive spectrometry, Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermo-gravimetric analysis, X-ray diffraction, and its mechanical properties were analyzed.  The results showed that all molecules in the hydrogel have good compatibility and they formed a honeycomb-like structure.  The hydrogel also showed good mechanical and thermal properties.  The in-vitro drug release of the hydrogel showed that the nano-insulin accorded with Fick's first law of diffusion and it has a high permeation rate (4.421 μg/(cm(2)hr)).  The authors concluded that these results suggested that the nano-insulin-loaded hydrogels are a promising non-invasive TDD system for diabetes chemotherapy.

Ito et al (2012) developed a dissolving microneedle (DM) application system, where 225 to 300 insulin-loaded DMs were formed on a chip.  After the heat-sealed sheet is removed, the system covered with the press-through package layer is put on the skin.  By pressing with the hand, insulin DMs were inserted into the skin.  Factors affecting the penetration depth of DM were studied using applicator in-vitro and in-vivo experiments.  The penetration depth was determined for rat and human skin.  Two-layered DM array chips were prepared to obtain complete absorption of insulin and administered to the rat abdominal skin.  Plasma glucose levels were measured for 6 hrs.  By comparing the hypoglycemic effect with that obtained after subcutaneous injection, relative pharmacological availability was determined.  The penetration depth increased from 21 +/- 3 μm to 63 +/- 2 μm in proportion to application speed to isolated rat skin, at 0.8 to 2.2 m/s.  Human skin showed similar results in the penetration depth.  The in-vivo penetration depth was dependent on the force (0.5 to 2.5 N) and duration (1 to 10 mins), as the secondary application force.  The penetration depth was 211 +/- 3 μm with 3-min duration in the in-vivo rat experiment.  Dissolving microneedle array chips having an insulin-loaded space of 181.2 +/- 4.2 and 209 +/- 3.9 μm were evaluated in the rat.  Relative pharmacological availability values of insulin from DMs were 98.1 +/- 0.8 % and 98.1 +/- 3.1 %, respectively.  The authors concluded that these findings suggested the usefulness of the 2-layered DM application system for the transdermal delivery of insulin.

Rosenfeld et al (2012) described patient perceptions regarding their experience and reported findings in a retrospective analysis of glycemic control in a cohort of patients who used the V-Go, a mechanical, 24-hr disposable, subcutaneous continuous insulin delivery device that delivers a preset basal infusion rate and on-demand insulin.  Patients used the V-Go and answered telephone surveys about their perception of device use.  Corresponding clinical data were retrospectively collected before V-Go initiation, after 12 weeks of use, at the end of treatment, and 12 weeks after discontinuation.  Analyses were performed with non-parametric statistical tests.  A total of 23 patients participated in this study.  Mean values of the following characteristics were documented: patient age, 61 years; body mass index, 30 kg/m2; diabetes duration, 16 years; duration of insulin therapy, 7 years; average duration of V-Go use, 194 days; and mean total daily insulin dose, 50 U at baseline, 46 U while on V-Go, and 51 U after stopping V-Go treatment.  Mean patient rating of the overall experience was 9.1 at 12 weeks on a scale from 1 to 10 (10 being most positive).  Mean hemoglobin A1c value decreased from baseline (8.8 % to 7.6 %; [p = 0.005]) while using the V-Go, and it increased to 8.2 % after treatment.  Fasting plasma glucose trended from 205 mg/dL at baseline to 135 mg/dL while using V-Go and increased to 164 mg/dL after V-Go was stopped.  Weight was essentially unchanged.  No differences in hypoglycemic events were found; site reactions were minor.  The authors concluded that glycemic control improved when patients were switched to the V-Go for insulin delivery, and it deteriorated when the V-Go was discontinued.  The main drawbacks of this study were its retrospective nature, small sample size, and short-term follow-up.  These preliminary findings need to be validated by well-designed studies.

Furthermore, UpToDate reviews on “General principles of insulin therapy in diabetes mellitus” (McCulloch, 2012a), “Insulin therapy in adults with type 1 diabetes mellitus” (McCulloch, 2012b), and “Insulin therapy in type 2 diabetes mellitus” (McCulloch, 2012c) do not mention the use of transdermal insulin delivery.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
Implantable Infusion Pumps:
CPT codes covered if selection criteria are met:
36563
36576
36578
36583
36590
62350 - 62351
62355
62360 - 62362
62365
62367 - 62370
95990 - 95991
96365 - 96368
96374 - 96376
96409 - 96411
96413 - 96417
96422 - 96425
96522
96523
99601 - 99602
HCPCS codes covered if selection criteria are met:
A4220 Refill kit for implantable infusion pump
A4221 Supplies for maintenance of drug infusion catheter, per week (list drug separately)
A4223 Infusion supplies not used with external infusion pump, per cassette or bag (list drugs separately)
A4300 Implantable access catheter, (e.g., venous, arterial, epidural subarachnoid, or peritoneal, etc) external access
A4301 Implantable access total catheter, port/reservoir (e.g., venous, arterial, epidural, subarachnoid, peritoneal, etc.)
A4305 Disposable drug delivery system, flow rate of 50 ml or greater per hour [not covered for intralesional administration of narcotic analgesics and anesthetics]
A4306 Disposable drug delivery system, flow rate of less than 50 ml per hour [not covered for intralesional administration of narcotic analgesics and anesthetics]
C1772 Infusion pump, programmable (implantable)
C1891 Infusion pump, nonprogrammable, permanent (implantable)
C2626 Infusion pump, nonprogrammable, temporary (implantable)
C8957 Intravenous infusion for therapy/diagnosis; initiation of prolonged infusion (more than 8 hours), requiring use of portable or implantable pump
E0782 Infusion pump, implantable, nonprogrammable (includes all components, e.g., pump, catheter, connectors, etc.)
E0783 Infusion pump system, implantable, programmable (includes all components, e.g., pump, catheter, connectors, etc.)
E0785 Implantable intraspinal (epidural/intrathecal) catheter used with implantable infusion pump, replacement
E0786 Implantable programmable infusion pump, replacement (excludes implantable intraspinal catheter)
J0475 Injection baclofen, 10 mg
J0476 Injection, baclofen, 50 mcg for intrathecal trial
J0735 Injection, clonidine HCl, 1 mg
J2270 Injection, morphine sulfate, up to 10 mg
J2271 Injection, morphine sulfate, 100 mg
J2275 Injection, morphine sulfate (preservative-free sterile solution), per 10 mg
J2278 Injection, ziconotide, 1 microgram
J9000 - J9999 Chemotherapy drugs
Q0081 Infusion therapy, using other than chemotherapeutic drugs, per visit
Q0084 Chemotherapy administration by infusion technique only, per visit
S0093 Injection, morphine sulphate, 500 mg (loading dose for infusion pump)
S5035 Home infusion therapy, routine service of infusion device (e.g., pump maintenance)
S5036 Home infusion therapy, repair of infusion device (e.g., pump repair)
S5497 Home infusion therapy, catheter care/maintenance, not otherwise classified; includes administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S5502 Home infusion therapy, catheter care/maintenance, implanted access device, includes administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment, (drugs and nursing visits coded separately), per diem (use this code for interim maintenance of vascular access not currently in use)
S5517 Home infusion therapy, all supplies necessary for restoration of catheter patency or declotting
S5518 Home infusion therapy, all supplies necessary for catheter repair
S9325 Home infusion therapy, pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem (do not use this code with S9326, S9327 or S9328)
S9326 Home infusion therapy, continuous (24 hours or more) pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9327 Home infusion therapy, intermittent (less than 24 hours) pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9328 Home infusion therapy, implanted pump pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9329 Home infusion therapy, chemotherapy infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem (do not use this code with S9330 or S9331)
S9330 Home infusion therapy, continuous (24 hours or more) chemotherapy infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9331 Home infusion therapy, intermittent (less than 24 hours) chemotherapy infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9363 Home infusion therapy, antispasmodic therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
HCPCS codes not covered for indications listed in the CPB:
J1817 Insulin for administration through DME (i.e., insulin pump) per 50 units
S9336 Home infusion therapy, continuous anticoagulant infusion therapy (e.g., Heparin), administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9353 Home infusion therapy, continuous insulin infusion therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
ICD-9 codes covered if selection criteria are met (not all inclusive):
153.0 - 154.8 Malignant neoplasm of colon, rectum, rectosigmoid junction, and anus
197.7 Secondary malignant neoplasm of liver, specified as secondary
333.91 Stiff-man syndrome
336.1 Vascular myelopathies
338.0 Central pain syndrome
338.21 - 338.29 Chronic pain
338.3 Neoplasm related pain (acute) (chronic)
338.4 Chronic pain syndrome
340 Multiple sclerosis
342.10 - 342.12 Spastic hemiplegia
343.0 - 343.9 Infantile cerebral palsy
344.00 - 344.09 Quadriplegia and quadriparesis
344.1 Paraplegia
728.85 Spasm of muscle
781.0 Abnormal involuntary movements
781.2 Abnormality of gait
806.00 - 806.09 Fracture of vertebral column with spinal cord injury
952.00 - 952.09 Spinal cord injury without evidence of spinal bone injury
ICD-9 codes not covered for indications listed in the CPB:
001.0 - 139.8 Infectious and parasitic diseases
249.00 - 249.91 Secondary diabetes mellitus
250.00 - 250.93 Diabetes mellitus
331.3 - 331.5 Hydrocephalus
415.11 - 415.19 Pulmonary embolism and infarction
444.0 - 445.89 Arterial embolism and thrombosis and atheroembolism
451.0 - 453.9 Phlebitis and thrombophlebitis and other venous embolism and thrombosis
536.3 Gastroparesis
648.00 - 648.04 Diabetes mellitus complicating pregnancy, childbirth, or the puerperium
648.80 - 648.84 Abnormal glucose tolerance complicating pregnancy, childbirth, or the puerperium
655.00 - 655.03 Central nervous system malformation in fetus affecting management of mother [hydrocephalus]
714.0 - 714.9 Rheumatoid arthritis and other inflammatory polyarthropathies
729.2 Neuralgia, neuritis, and radiculitis, unspecified
741.00 – 741.03 Spina bifida with hydrocephalus
742.3 Congenital hydrocephalus
783.22 Underweight
V12.51 Personal history of venous thrombosis and embolism
V12.52 Personal history of thrombophlebitis
V14.5 Personal history of allergy to narcotic agent
V14.6 Personal history of allergy to analgesic agent
V45.00 - V45.09 Cardiac device in situ
V45.85 Insulin pump status
V58.67 Long-term (current) use of insulin
Other ICD-9 codes related to the CPB:
V10.05 Personal history of malignant neoplasm of large intestine
V10.06 Personal history of malignant neoplasm of rectum, rectosigmoid junction, and anus
V53.09 Fitting and adjustment of other devices related to nervous system and special senses
V58.11 - V58.12 Encounter for antineoplastic chemotherapy and immunotherapy
External Infusion Pumps:
CPT codes covered if selection criteria are met:
96365 - 96368
96374 - 96376
96409 - 96411
96413 - 96417
96422 - 96425
96521
99601 - 99602
HCPCS codes covered if selection criteria are met:
A4221 Supplies for maintenance of drug infusion catheter, per week (list drugs separately)
A4222 Infusion supplies for external drug infusion pump, per cassette or bag (list drugs separately)
A4230 Infusion set for external insulin pump, nonneedle cannula type
A4231 Infusion set for external insulin pump, needle type
A4232 Syringe with needle for external insulin pump, sterile, 3cc
A4300 Implantable access catheter, (e.g., venous, arterial, epidural subarachnoid, or peritoneal, etc) external access
A4301 Implantable access total catheter, port/reservoir (e.g., venous, arterial, epidural, subarachnoid, peritoneal, etc.)
A4305 Disposable drug delivery system, flow rate of 50 ml or greater per hour [not covered for intralesional administration of narcotic analgesics and anesthetics]
A4306 Disposable drug delivery system, flow rate of less than 50 ml per hour [not covered for intralesional administration of narcotic analgesics and anesthetics]
A9274 External ambulatory insulin delivery system, disposable, each, includes all supplies and accessories
C8957 Intravenous infusion for therapy/diagnosis; initiation of prolonged infusion (more than 8 hours), requiring use of portable or implantable pump
E0779 Ambulatory infusion pump, mechanical, reusable, for infusion 8 hours or greater
E0780 Ambulatory infusion pump, mechanical, reusable, for infusion less than 8 hours
E0781 Ambulatory infusion pump, single or multiple channels, electric or battery operated, with administrative equipment, worn by patient
E0784 External ambulatory infusion pump, insulin [V-Go disposable insulin delivery device not covered]
E1520 Heparin infusion pump for hemodialysis
J0475 Injection baclofen, 10 mg
J0476 Injection baclofen, 50 mcg for intrathecal trial
J0895 Injection, defoxamine mesylate [Desferal], 500 mg
J1250 Injection, Dobutamine HCL, per 250 mg
J1644 Injection, Heparin sodium, per 1,000 units
J1815 Injection insulin, per 5 units
J1817 Insulin for administration through DME (i.e., insulin pump) per 50 units
J2260 Injection, milrinone lactate, 5 mg
J9000 - J9999 Chemotherapy drugs
K0601 - K0605 Replacement battery for external infusion pump owned by patient
Q0081 Infusion therapy, using other than chemotherapeutic drugs, per visit
Q0084 Chemotherapy administration by infusion technique only, per visit
S9140 Diabetic management program, follow-up visit to non-MD provider
S9141 Diabetic management program, follow-up visit to MD provider
S9145 Insulin pump initiation, instruction in initial use of pump (pump not included)
S9336 Home infusion therapy, continuous anticoagulant infusion therapy (e.g., Heparin), administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9345 Home infusion therapy, anti-hemophilic agent infusion therapy (e.g., factor VIII); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits codes separately), per diem
S9346 Home infusion therapy, alpha-1-proteinase inhibitor (e.g., Prolastin); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9347 Home infusion therapy, uninterrupted, long-term, controlled rate intravenous or subcutaneous infusion therapy (e.g., epoprostenol); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9348 Home infusion therapy, sympathomimetic/inotropic agent infusion therapy (e.g., Dobutamine); administrative services, professional pharmacy services, care coordination, all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9353 Home infusion therapy, continuous insulin infusion therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9355 Home infusion therapy, chelation therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9357 Home infusion therapy, enzyme replacement intravenous therapy; (e.g., Imiglucerase); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9359 Home infusion therapy, antitumor necrosis factor intravenous therapy; (e.g., Infliximab); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9363 Home infusion therapy, anti-spasmodic therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9373 Home infusion therapy, hydration therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem (do not use with hydration therapy codes S9374-S9377 using daily volume scales)
S9374 Home infusion therapy, hydration therapy; 1 liter per day, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9375 Home infusion therapy, hydration therapy; more than 1 liter but no more than 2 liters per day, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9376 Home infusion therapy, hydration therapy; more than 2 liters but no more than 3 liters per day, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9377 Home infusion therapy, hydration therapy; more than 3 liters per day, administrative services, professional pharmacy services, care coordination, and all necessary supplies (drugs and nursing visits coded separately), per diem
S9455 Diabetic management program, group session
S9460 Diabetic management program, nurse visit
S9490 Home infusion therapy, corticosteroid infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9494 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately, per diem) (do not use with home infusion codes for hourly dosing schedules S9497 - S9504)
S9497 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 3 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9500 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 24 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9501 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 12 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9502 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 8 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9503 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 6 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9504 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 4 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
Other HCPCS codes related to the CPB:
E0607 Home blood glucose monitor
J1642 Injection, heparin sodium, (heparin lock flush), per 10 units
ICD-9 codes covered if selection criteria are met (not all-inclusive):
001.0 - 139.8 Infectious and parasitic diseases
153.0 - 154.8 Malignant neoplasm of colon, rectum, rectosigmoid junction, and anus
155.0 - 155.2 Malignant neoplasm of liver and intrahepatic bile ducts
249.00 - 249.91 Secondary diabetes mellitus
250.00 - 250.93 Diabetes mellitus
275.0 Disorders of iron metabolism
338.3 Neoplasm related pain (acute) (chronic)
415.11 - 415.19 Pulmonary embolism and infarction
416.0 Primary pulmonary hypertension
416.8 Other chronic pulmonary heart diseases
444.0 - 445.89 Arterial embolism and thrombosis and atheroembolism
451.0 - 453.9 Phlebitis and thrombophlebitis and other venous embolism and thrombosis
648.00 - 648.04 Diabetes mellitus complicating pregnancy, childbirth, or the puerperium
648.80 - 648.84 Abnormal glucose tolerance complicating pregnancy, childbirth, or the puerperium
671.00 - 671.94 Venous complications in pregnancy and the puerperium
673.00 - 673.84 Obstetrical pulmonary embolism
964.0 Poisoning by iron and its compounds
V58.67 Long-term (current) use of insulin
Other ICD-9 codes related to the CPB:
V45.85 Insulin pump status
V58.11 - V58.12 Encounter for antineoplastic chemotherapy and immunotherapy


The above policy is based on the following references:
  1. Gianino JM, York MM, Paice JA, et al. Quality of life: Effect of reduced spasticity from intrathecal baclofen. J Neurosci Nurs. 1998;30(1):47-54.
  2. Jaremko J, Rorstad O. Advances toward the implantable artificial pancreas for treatment of diabetes. Diabetes Care. 1998;21(3):444-450.
  3. Belicar P, Lassmann-Vague V. Local adverse events associated with long-term treatment by implantable insulin pumps. The French EVADIAC Study Group experience. Evaluation dans le Diabete du Traitement par Implants Actifs. Diabetes Care. 1998;21(2):325-326.
  4. Harvey SC, O'Neil MG, Pope CA, et al. Continuous intrathecal meperidine via an implantable infusion pump for chronic, nonmalignant pain. Ann Pharmacother. 1997;31(11):1306-1308.
  5. Armstrong RW, Steinbok P, Cochrane DD, et al. Intrathecally administered baclofen for treatment of children with spasticity of cerebral origin. J Neurosurg. 1997;87(3):409-414.
  6. Lassmann-Vague V, Guerci B, Hanaire-Broutin H, et al. Use of implantable insulin pumps: The EVADIAC position. Recommendations of ALFEDIAM (French Language Association for the Study of Diabetes and Metabolic Diseases). Evaluation dans le Diabete du Traitement par Implants Actifs. Diabetes Metab. 1997;23(3):234-250.
  7. Albright AL. Intrathecal baclofen in cerebral palsy movement disorders. J Child Neurol. 1996;11 Suppl 1:S29-S35.
  8. Saudek CD, Duckworth WC, Giobbie-Hurder A, et al. Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent diabetes mellitus: A randomized clinical trial. Department of Veterans Affairs Implantable Insulin Pump Study Group. JAMA. 1996;276(16):1322-1327.
  9. Krames, E. Intraspinal opioid therapy for chronic non-malignant pain: Current practice and clinical guidelines. J Pain Symptom Manage. 1996;11(6):333-352.
  10. Vague P, Lassmann-Vague V, Belicar P, Alessis C. The implantable insulin pump in the treatment of diabetes. Hopes and reality? Bull Acad Natl Med. 1996 ;180(4):831-841; discussion 841-843.
  11. Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: Report of 38 cases. Pain. 1986;25:171-186.
  12. Coombs DW, Saunders RL, Gaylor MS, et al. Relief of continuous chronic pain by intraspinal narcotics infusion via an implanted reservoir. JAMA. 1983;250(17):2336-2339.
  13. Martin JK, O'Connell MJ, Wieand HS, et al. Intra-arterial floxuridine vs systemic fluorouracil for hepatic metastases from colorectal cancer. Arch Surg. 1990;125(8):1022-1027.
  14. Rougier P, Laplanche A, Huguier M, et al. Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: Long term results of a prospective randomized trial. J Clin Oncol. 1992;10(7):1112-1118.
  15. U.S. Department of Health and Human Services, Health Care Financing Administration (HCFA). Infusion pumps. Medicare Coverage Issues Manual §60-14. HCFA Pub. 6. Baltimore, MD: HCFA; 2000.
  16. Doci R, Bignami P, Bozzetti F, et al. Intrahepatic chemotherapy for unresectable hepatocellular carcinoma. Cancer. 1988;61(10):1983-1987.
  17. No authors listed. Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. Meta-analysis Group in Cancer. J Natl Cancer Inst. 1996;88(5):252-258.
  18. Durand-Zaleski I, Roche B, Buyse M, et al. Economic implications of hepatic arterial infusion chemotherapy in treatment of nonresectable colorectal liver metastases. Meta-analysis Group in Cancer. J Natl Cancer Inst. 1997;89(11):790-795.
  19. Lorenz M, Staib-Sebler E, Koch B, et al. The value of postoperative hepatic arterial infusion following curative liver resection. Anticancer Res. 1997;17(5B):3825-3833.
  20. National Heritage Insurance Company (NHIC). External infusion pumps. Local Coverage Determination No. L5044. Durable Medical Equipment Medicare Administrative Contractor (DME MAC) Jurisdiction A. Chico, CA: NHIC; revised March 1, 2008. 
  21. Urabe T, Kaneko S, Matsushita E, et al. Clinical pilot study of an intrahepatic arterial chemotherapy with methotrexate, 5-fluorouracil, cisplatin and subcutaneous interferon-alpha-2b for patients with locally advanced hepatocellular carcinoma. Oncology. 1998;55(1):39-47.
  22. Rougier P. Are there indications for intraarterial hepatic chemotherapy or isolated liver perfusion? The case of liver metastases from colorectal cancer. Recent Results Cancer Res. 1998;147:3-12.
  23. Okada S. Chemotherapy in hepatocellular carcinoma. Hepatogastroenterology. 1998;45 (Suppl 3):1259-1263.
  24. Sakai Y, Izumi N, Tazawa J, et al. Treatment for advanced hepatocellular carcinoma by transarterial chemotherapy using reservoirs or one-shot arterial chemotherapy. J Chemother. 1997;9(5):347-351.
  25. Soga K, Nomoto M, Ichida T, et al. Clinical evaluation of transcatheter arterial embolization and one-shot chemotherapy in hepatocellular carcinoma. Hepatogastroenterology. 1988;35(3):116-120.
  26. American Diabetes Association: Clinical practice recommendations 1995. Diabetes Care. 1995;18(Supp 1):1-96.
  27. U.S. Department of Health and Human Services, Health Care Financing Administration (HCFA). Continuous subcutaneous insulin infusion pump. Decision Memorandum. Issue # CAG-00041. Baltimore, MD: HCFA; August 26, 1999. Available at: http://www.hcfa.gov/quality/8b3% 2Di2.htm. Accessed September 28, 1999.
  28. The Diabetes Control and Complications Trial Research Group. Implementation of treatment protocols in the Diabetes Control and Complications Trial. Diabetes Care. 1995;18(3):361-376.
  29. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986.
  30. Marcus AO, Fernandez MP. Insulin pump therapy. Acceptable alternative to injection therapy. Postgrad Med. 1996;99(3):1-7.
  31. Koivisto VA, Yki-Järvinen H, Helve E, et al. Pathogenesis and prevention of the dawn phenomenon in diabetic patients treated with CSII. Diabetes. 1986;35:78-82.
  32. Bode B, Steed RD, Davidson PC. Reduction in severe hypoglycemia with long-term continuous subcutaneous insulin infusion in type I diabetes. Diabetes Care. 1996;19(4):324-327.
  33. Farkas-Hirsch R, Hirsch IB. The question is answered. Now what?. Diabetes Care. 1994;17(3):237-238.
  34. Eichner HL, Selam J, Holleman CB, et al. Reduction of severe hypoglycemic events in type I (insulin dependent) diabetic patients using continuous subcutaneous insulin infusion. Diabetes Res. 1988;8(4):189-193.
  35. Kitzmiller JL, Gavin LA, Gin GD, et al. Preconception care of diabetes: Glycemic control prevents congenital anomalies. JAMA. 1991;265(6):731-736.
  36. Reichard P. Are there any glycemic thresholds for the serious microvascular diabetic complications? J Diab Comp. 1995;9:25-30.
  37. Agency for Health Care Policy and Research (AHCPR). Reassessment of external insulin infusion pumps. AHCPR Assessment No. 9. Rockville, MD: AHCPR; July 1991.
  38. American Medical Association (AMA). Continuous subcutaneous insulin infusion. Diagnostic and Therapeutic Technology Assessment. Chicago, IL: AMA; 1989.
  39. U.S. Department of Health and Human Services, Health Care Financing Administration (HCFA). Medicare will cover insulin pumps for beneficiaries. Press Release. Baltimore, MD: HCFA; September 24, 1999. Available at: http://www.hcfa.gov/news/pr1999/pr990924.htm. Accessed September 28, 1999.
  40. National Institute for Clinical Excellence (NICE). Guidance on the use of continuous subcutaneous insulin infusion for diabetes. Technology Appraisal Guidance No. 57. London, UK: NICE; February 2003. Available at: http://www.nice.org.uk/pdf/57_Insulin_pumps_fullguidance.pdf. Accessed October 10, 2003.
  41. Williams JE, Louw G, Towlerton G. Intrathecal pumps for giving opioids in chronic pain: A systematic review. Health Technol Assess. 2000;4(32):iii-iv, 1-65.
  42. Institute for Clinical Systems Improvement (ICSI). Dorsal rhizotomy and intrathecal baclofen for lower extremity spasticity associated with cerebral palsy. Technology Assessment Report. Bloomington, MN: ICSI; 2000.
  43. Villanueva E, Anderson J. Intrathecal baclofen for spasticity. Evidence Centre Report. Clayton, VIC: Monash Institute of Public Health & Health Services Research, Centre for Clinical Effectiveness (CCE); 2000.
  44. American Diabetes Association. Continuous subcutaneous insulin infusion. Diabetes Care. 2003;26 Suppl 1:S125.
  45. Medtronic MiniMed. The Paradigm Wireless Diabetes Management System. Northridge, CA: Medtronic MiniMed; 2004. Available at: http://www.minimed.com/patientfam/
    pf_ipt_paradigm_pump_overview.shtml. Accessed February 24, 2004.
  46. Centers for Medicare & Medicaid Services (CMS). Decision memo for insulin pump: C-peptide levels as a criterion for use (CAG-00092R). Baltimore, MD: CMS; December 17, 2004. Available at: http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=109. Accessed March 4, 2005.
  47. Sampson FC, Hayward A, Evans G, et al. The effectiveness of intrathecal baclofen in the management of patients with severe spasticity. InterTASC Report No. 06/2000. Sheffield, UK: Trent Institute for Health Services Research, Universities of Leicester, Nottingham and Sheffield; 2000.
  48. Oduneye F. Insulin pumps, conventional and intensive multiple injection insulin therapy for type 1 diabetes mellitus. Bazian Ltd., eds. London, UK: Wessex Institute for Health Research and Development, University of Southampton; 2002.
  49. Bayram N, van Wely M, van der Veen F. Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev. 2004;(1):CD000412.
  50. Colquitt JL, Green C, Sidhu MK, et al. Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes. Health Technol Assess. 2004;8(43):iii, 1-171.
  51. Hansel DE, Hansel CR, Shindle MK, et al. Oral baclofen in cerebral palsy: Possible seizure potentiation? Pediatr Neurol. 2003;29(3):203-206.
  52. Simpson B, Middleton P, Maddern G. Implantable spinal infusion devices for chronic pain and spasticity: An accelerated systematic review. Stepney, SA: Australian Safety and Efficacy Register of New Interventional Procedures - Surgical (ASERNIP-S); 2003.
  53. Taricco M, Adone R, Pagliacci C, Telaro E. Pharmacological interventions for spasticity following spinal cord injury. Cochrane Database Syst Rev. 2000;(2):CD001131.
  54. Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev. 2003;(4):CD001332.
  55. Andersen J, Hartling L, Tjosvold L, Watt J. Oral baclofen for the management of spasticity in children with cerebral palsy (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2005;(3):CD005357.
  56. Misso ML, O'Connor DA, Egberts KJ, Shaw J. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2005;(1):CD005103.
  57. Rice JE, O'Donnell ME. Intrathecal baclofen for treating spasticity in children with cerebral palsy (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2004;(1):CD004552.
  58. Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat. Intrathecal baclofen pump for spasticity. Health Technology Review. Toronto, ON: Ontario Ministry of Health and Long-Term Care; May 2005.
  59. Cote B, St-Hilaire C. Comparison of the insulin pump and multiple daily insulin injections in intensive therapy for type 1 diabetes. Montreal, QC: Agence d'Evaluation des Technologies et des Modes d'Intervention en Sante (AETMIS); 2004.
  60. Roberts DJ, Rees D, Howard J, et al. Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia. Cochrane Database Syst Rev. 2005;(4):CD004450.
  61. Eisenach JC, DuPen S, Dubois M, et al. Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group. Pain. 1995;61(3):391-399.
  62. Boswell G, Bekersky I, Mekki Q, Eisenach J. Plasma concentrations and disposition of clonidine following a constant 14-day epidural infusion in cancer patients. Clin Ther. 1997;19(5):1024-1030.
  63. Portas M, Marty JY, Buttin C, et al. Refractory pain in children with cancer: Role of peridural analgesia. Arch Pediatr. 1998;5(8):851-860.
  64. Mercadante S. Neuraxial techniques for cancer pain: An opinion about unresolved therapeutic dilemmas. Reg Anesth Pain Med. 1999;24(1):74-83.
  65. Mercadante S, Portenoy RK. Opioid poorly-responsive cancer pain. Part 3. Clinical strategies to improve opioid responsiveness. J Pain Symptom Manage. 2001;21(4):338-354.
  66. Exner HJ, Peters J, Eikermann M. Epidural analgesia at end of life: Facing empirical contraindications. Anesth Analg. 2003;97(6):1740-1742.
  67. Wasiak J. Can clonidine be used in effectively in epidural and intrathecal catheters? Evidence Centre Report. Clayton, VIC: Monash Institute of Public Health & Health Services Research, Centre for Clinical Effectiveness; March 10, 2000.
  68. Farrar D, Tuffnell DJ, West J. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. Cochrane Database Syst Rev. 2007;(3):CD005542.
  69. Mukhopadhyay A, Farrell T, Fraser RB, Ola B. Continuous subcutaneous insulin infusion vs intensive conventional insulin therapy in pregnant diabetic women: A systematic review and metaanalysis of randomized, controlled trials. Am J Obstet Gynecol. 2007;197(5):447-456.
  70. Hammond P. Continuous subcutaneous insulin infusion: Short-term benefits apparent, long-term benefits speculative. Br J Diabetes Vasc Dis. 2004;4(2):104-108.
  71. Brennan PM, Whittle IR. Intrathecal baclofen therapy for neurological disorders: A sound knowledge base but many challenges remain. Br J Neurosurg. 2008;22(4):508-519.
  72. Shilt JS, Lai LP, Cabrera MN, et al. The impact of intrathecal baclofen on the natural history of scoliosis in cerebral palsy. J Pediatr Orthop. 2008;28(6):684-687.
  73. Caird MS, Palanca AA, Garton H, et al. Outcomes of posterior spinal fusion and instrumentation in patients with continuous intrathecal baclofen infusion pumps. Spine. 2008;33(4):E94-E99.
  74. Pickup JC, Renard E. Long-acting insulin analogs versus insulin pump therapy for the treatment of type 1 and type 2 diabetes. Diabetes Care. 2008;31 Suppl 2:S140-145.
  75. Raskin P, Bode BW, Marks JB, et al. Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes: A randomized, parallel-group, 24-week study. Diabetes Care. 2003;26(9):2598-2603.
  76. Fatourechi MM, Kudva YC, Murad MH, et al. Clinical review: Hypoglycemia with intensive insulin therapy: A systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections.
    J Clin Endocrinol Metab. 2009;94(3):729-740.
  77. Rodbard HW, Blonde L, Braithwaite SS, et al.; AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13 Suppl 1:1-68.
  78. Berthe E, Lireux B, Coffin C, et al. Effectiveness of intensive insulin therapy by multiple daily injections and continuous subcutaneous infusion: A comparison study in type 2 diabetes with conventional insulin regimen failure. Horm Metab Res. 2007;39(3):224-229.
  79. Parkner T, Laursen T, Vestergaard ET, et al. Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long-acting insulin in Type 2 diabetes. Diabet Med. 2008;25(5):585-591.
  80. Herman WH, Ilag LL, Johnson SL, Martin CL, et al. A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes. Diabetes Care. 2005;28(7):1568-1573.
  81. National Institute for Health and Clinical Excellence (NICE). Continuous subcutaneous insulin infusion for the treatment of diabetes mellitus. Review of technology appraisal guidance 57. NICE Technology Appraisal Guidance 151. London, UK: NICE; July 2008.
  82. Hoving MA, van Raak EP, Spincemaille GH, et al. Efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy: A randomised controlled trial. Eur J Paediatr Neurol. 2009;13(3):240-246.
  83. Logtenberg SJ, Kleefstra N, Houweling ST, et al. Improved glycemic control with intraperitoneal versus subcutaneous insulin in type 1 diabetes: A randomized controlled trial. Diabetes Care. 2009;32(8):1372-1377.
  84. Lassmann-Vague V, Clavel S, Guerci B, et al; Société francophone du diabète (ex ALFEDIAM). When to treat a diabetic patient using an external insulin pump. Expert consensus. Société francophone du diabète (ex ALFEDIAM) 2009. Diabetes Metab. 2010;36(1):79-85.
  85. Cummins E, Royle P, Snaith A, et al. Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: Systematic review and economic evaluation. Health Technol Assess. 2010;14(11):iii-iv, xi-xvi, 1-181.
  86. Grunberger G, Bailey TS, Cohen AJ, et al.; AACE Insulin Pump Management Task Force. Statement by the American Association of Clinical Endocrinologists Consensus Panel on insulin pump management. Endocr Pract. 2010;16(5):746-762.
  87. Pickup JC. Management of diabetes mellitus: Is the pump mightier than the pen? Nat Rev Endocrinol. 2012;8(7):425-433.
  88. Alsaleh FM, Smith FJ, Taylor KM. Experiences of children/young people and their parents, using insulin pump therapy for the management of type 1 diabetes: Qualitative review. J Clin Pharm Ther. 2012;37(2):140-147.
  89. Zu Y, Zhang Y, Zhao X, et al. Preparation and characterization of chitosan-polyvinyl alcohol blend hydrogels for the controlled release of nano-insulin. Int J Biol Macromol. 2012;50(1):82-87.
  90. Ito Y, Nakahigashi T, Yoshimoto N, et al. Transdermal insulin application system with dissolving microneedles. Diabetes Technol Ther. 2012;14(10):891-899.
  91. Rosenfeld CR, Bohannon NJ, Bode B, et al. TheV-Go insulin delivery device used in clinical practice: Patient perception and retrospective analysis of glycemic control. Endocr Pract. 2012;18(5):660-667.
  92. McCulloch DK. General principles of insulin therapy in diabetes mellitus. Last reviewed December 2012a. UpToDate Inc. Waltham, MA.
  93. McCulloch DK. Insulin therapy in adults with type 1 diabetes mellitus. Last reviewed December 2012b. UpToDate Inc. Waltham, MA.
  94. McCulloch DK. Insulin therapy in type 2 diabetes mellitus. Last reviewed December 2012c. UpToDate Inc. Waltham, MA.
  95. Valentino L, Pillay KV, Walker J. Managing chronic nonmalignant pain with continuous intrathecal morphine. J Neurosci Nurs. 1998;30(4):233-239, 243-244.
  96. Angel IF, Gould HJ Jr, Carey ME. Intrathecal morphine pump as a treatment option in chronic pain of nonmalignant origin. Surg Neurol. 1998;49(1):92-98; discussion 98-99.
  97. Harvey SC, O'Neil MG, Pope CA, et al. Continuous intrathecal meperidine via an implantable infusion pump for chronic, nonmalignant pain. Ann Pharmacother. 1997;31(11):1306-1308.
  98. Yoshida GM, Nelson RW, Capen DA, et al. Evaluation of continuous intraspinal narcotic analgesia for chronic pain from benign causes. Am J Orthop. 1996;25(10):693-694.
  99. Winkelmuller M, Winkelmuller W. Long-term effects of continuous intrathecal opioid treatment in chronic pain of nonmalignant etiology. J Neurosurg. 1996;85(3):458-467.
  100. Levy R, Leiphart J, Dills C. Analgesic action of acute and chronic intraspinally administered opiate and alpha 2-adrenergic agonists in chronic neuropathic pain. Stereotact Funct Neurosurg. 1994;62(1-4):279-289.
  101. Ebel H, Buschmann D, Conzen M, et al. [Initial experiences with implantable pump systems for intrathecal therapy of chronic pain conditions] Nervenarzt. 1993;64(7):468-473.
  102. Krames ES. Intrathecal infusional therapies for intractable pain: Patient management guidelines. J Pain Symptom Manage. 1993;8(1):36-46.
  103. Hassenbusch SJ, Stanton-Hicks MD, Soukup J, et al. Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions for intractable non-cancer pain. Neurosurgery. 1991;29(1):76-82.
  104. Rodriguez Lopez MJ, de la Torre Liebanas M, Sanchez-Guijo Bernal JJ, et al. [Treatment of chronic pain of oncologic origin with epidural or intrathecal morphine administered by continuous or programmable flow implanted pumps] Rev Esp Anestesiol Reanim. 1990;37(6):339-345.
  105. Hassenbusch SJ, Pillay PK, Magdinec M, et al. Constant infusion of morphine for intractable cancer pain using an implanted pump. J Neurosurg. 1990;73(3):405-409.
  106. Robert G. Implantable infusion devices (IIPs) for long-term pain management. DEC Report 55. Southampton, UK: Wessex Institute for Health Research and Development (WIHRD); 1996.
  107. Williams J E, Louw G, Towlerton G. Intrathecal pumps for giving opioids in chronic pain: A systematic review. Health Technol Assess. 2000;4(32):1-65.
  108. Simpson B, Middleton P, Maddern G. Implantable spinal infusion devices for chronic pain and spasticity: A accelerated systematic review. ASERNIP-S Report No. 42. North Adelaide, SA: Royal Australasian College of Surgeons, Australian Safety and Efficacy Register of New Interventional Procedures (ASERNIP) - Surgical; 2003.
  109. Turk DC, Wilson HD, Cahana A, et al. Treatment of chronic non-cancer pain.  Lancet. 2011;377(9784):2226-2235.


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