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Targeted Drug Delivery

  • Education and Training
  • Efficacy
  • Products and Procedures
  • Reimbursement and Practice Management
  • Indications, Safety, and Warnings
  • Patient Selection

    There are many factors critical to the success of intrathecal drug delivery (also known as targeted drug delivery). One of the most important is patient selection.

    Details

    The overall goal for patient selection for targeted drug delivery (also known as intrathecal drug delivery) is to choose those patients most likely to experience therapeutic success while reducing the likelihood of risks, complications, and adverse events. A careful assessment by a multidisciplinary team, and discussion of the patient’s expectations and goals, will help identify appropriate candidates for targeted drug delivery.

    Choosing an Optimal Patient
    View

    Dr. Wellington: Choosing an Optimal Patient

    (1:23, 16.9 MB)

    Dr. Joshua Wellington describes ideal targeted drug delivery patients for both chronic intractable pain and cancer pain.

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    In general, targeted drug delivery can be considered for patients with chronic pain who have:

    • Chronic, intractable pain
    • Not received adequate relief from more conservative treatments
    • No untreated drug addiction
    • No contraindications to implantation

    Additionally:

    • There is objective evidence of pathology concordant with the pain complaint
    • Surgical intervention is not indicated
    • A psychological evaluation of the patient has been completed and clearance given

    Guidelines based on an experience- and knowledge-based evaluation of available evidence were published in 2010.1 These consensus guidelines suggest a thorough, multifaceted approach to the patient selection process for intrathecal drug delivery.

    Appropriate patient selection for intrathecal drug delivery includes considerations of:1

    • Preexisting medical comorbidities
    • Psychological status
    • Associated social, technical, and economic issues
    • Response to a trial assessment

     

    References
    1. Deer TR, Smith HS, Cousins M, et al. Noncancer pain for intrathecal drug delivery. Pain Physician. 2010;13:E175-E213.

    Patient Assessment

    The key steps involved with patient selection and screening tests are:

    • Review patient selection criteria
    • Qualify the patient
    • Provide patient and caregiver education
    • Conduct the screening test

    General Patient Selection Criteria

    Managing a patient’s pain entails a complete evaluation of the pain and the patient’s medications. The value of a multidisciplinary approach to assess chronic pain cannot be overstated. There are different intrathecal drug delivery selection criteria for patients with cancer pain versus patients with chronic intractable pain.


    Cancer Pain

    Patient selection for intrathecal drug delivery for cancer pain (i.e., pain due to cancer or its therapies) is usually guided by the severity of the pain, the nature of the pain, life expectancy, and the location of the pain.

    Selection criteria for patients with cancer pain include:

    • Patient experiences inadequate pain relief and/or intolerable side effects from systemic opioid therapy
    • Patient’s life expectancy is greater than 3 months
    • Patient’s body size is sufficient enough to accept the bulk and weight of the pump
    • No contraindications to surgery or the therapy exist
    • Patient has a favorable response to the screening test

    Patients with cancer are often reluctant to report the extent of their pain and, therefore, are at a particularly high risk for undertreatment of pain. Among patients with metastatic disease, 1 in 3 will have pain that interferes with the way they live.1 The cost of inadequate pain control and the related side effects of pain medications is high, both in terms of impaired function and quality of life.2-4

    It is important to consider increased assessment and referral vigilance for women,2,5 minorities,1,2,5-7 and the elderly,2,5-6 who have been shown to be at increased risk for inadequate analgesia.


    Chronic Intractable Pain

    Patient selection for the treatment of chronic intractable pain requires a closer examination of criteria. In most cases, a psychological evaluation is indicated to examine factors such as patient expectations, psychosomatic components of the pain, and secondary gain motivation.

    Selection criteria for patients with chronic intractable pain include:

    • Patient experiences inadequate pain relief and/or intolerable side effects from systemic opioid therapy
    • Patient has objective evidence of pathology
    • Patient obtains psychological clearance
    • Patient has no untreated substance abuse
    • Patient has sufficient body size to accept the bulk and weight of the pump
    • Clear therapy goals and realistic expectations have been established
    • No contraindications to surgery or the therapy exist
    • Patient has a favorable response to the screening test

    Contraindications

    The only absolute contraindication to the use of intraspinal morphine is a known allergy to morphine. For complete prescribing information, refer to the drug labeling.

    Qualify the Patient

    When evaluating a patient with chronic intractable pain for intrathecal drug delivery, there are four primary assessments on which to focus:

    • Pain
    • Functional
    • Psychological
    • Medical and radiographic

    The table below provides a checklist of assessments for use during patient selection for intrathecal drug delivery.

     
    Pain Assessment
    • Complete baseline pain assessment
      Assessment of pain is difficult to standardize. As the pain state changes, the patient's baseline usually changes as well.
    • Review patient's current situation
      For example, is the patient receiving oral, intravenous, or intramuscular opioids without adequate pain relief at reasonable doses? Does the patient have pain relief but with side effects that limit the desired activity level?
    • Obtain supplemental opiate and non-opiate history
    • Assess signs and symptoms
      Consider the intensity, distribution, and impact of pain
    Functional Assessment
    • Obtain patient functional history
      Consider using a questionnaire that inquires into personal care, sleeping, sex life, social life, and mobility
    Psychological Assessment
    • Complete psychological evaluation of patients with chronic intractable pain
    • Establish diagnosis
    • Establish patient has realistic expectations of the therapy, no secondary gain intentions, and no untreated psychological conditions that would be contraindicated for an implantable therapy
    Medical Assessment
    • Evaluate for medical contraindications to surgery
    • Conduct physical examination
    • Evaluate radiographically for patient spinal canal, if indicated

    Early on in the patient evaluation, clinicians should:

    • Obtain patient history and conduct physical examination
    • Assess and document patient’s pain-related symptoms
    • Evaluate other appropriate and less invasive therapies
    • Assess patient motivation and commitment to intrathecal drug delivery therapy

    Reasonable goals for intrathecal drug delivery should be established and documented and may include:

    • Reduction in pain
    • Reduction in use of oral medication and side effects
    • Improved function
    • Improved quality of life
    Setting Patient Goals
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    Dr. Caraway: Setting Patient Goals

    (2:28, 30.3 MB)

    Dr. David Caraway optimizes therapy outcomes through setting patient goals and expectations, paired with a psychological exam.

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    Preparing patients for the psychological assessment helps reduce resistance and promote cooperation.8 During the evaluation, clinicians should communicate that the psychological assessment:8

    • Is used to explore contributing factors of the pain and is not intended to prove that the pain is “all in the patient’s head”
    • Will help select the right treatment for managing the pain and related symptoms (e.g. fatigue, depression)
    • Use validated assessment tools

    Especially for chronic intractable pain patients, consider if:

    • Patient will benefit from the pain relief that the pump provides
    • Concurrent behavioral, coping, or other therapies would provide a better outcome

    Clinicians should:

    • Assess existence of significant psychological signs, drug addiction or behavioral problems, and unresolved issues of secondary gain
    • Identify and treat psychological co-morbidities prior to therapy
    • Evaluate patient willingness, understanding, and competency to actively participate in their intrathecal drug delivery therapy
    • Establish a baseline against which to measure improvement

    Patient and caregiver expectations should also be realistic. Candidates for intrathecal drug delivery must:

    • Be able to determine specific, measurable goals and expectations for intrathecal drug delivery
    • Want a decrease in pain and an improvement in the ability to function
    • Understand that pain has multiple components
    • Express realistic expectations about treatment outcomes
    • Be able and willing to participate in therapy and rehabilitation when appropriate

     

    Provide Patient and Caregiver Education

    Patient education is critical to managing patient expectations and the long-term success of intrathecal drug delivery. Education begins at the initial assessment and continues throughout all phases of intrathecal drug delivery. Equally important to the clinical selection of the patient, is the time to allow the patient to make an educated decision concerning his or her therapy.

    The patient, family, and caregiver need to understand the need for commitment to intrathecal drug delivery, including the importance of keeping refill appointments, and reporting unusual or unexpected symptoms. They need to be aware of the signs and symptoms of opioid and sedative drug overdose and be instructed to seek emergency medical assistance when signs or symptoms first appear.

    Patient Education
    View

    Dr. Hatheway: Patient Education

    (1:55, 23.6 MB)

    Dr. John Hatheway explains why educating the patient on targeted drug delivery and opioid taper helps ensure an informed decision.

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    Clinicians should make sure the patient understands:

    • The goal of intrathecal drug delivery is to reduce rather than eliminate pain
    • Resuming activities that the patient cannot currently perform is a good outcome
    • Supportive medical treatment (e.g. adjuvant non-opioid medication) may be required

    Refer to the SynchroMed II Infusion System Clinical Reference Guide for detailed information and procedures on patient selection for intrathecal drug delivery. The Patient Education Checklist for Trial, located in the appendix of the Clinical Reference Guide, provides a detailed list of educational topics for use during patient selection for intrathecal drug delivery.

    References
    1. Cleeland CS, Gonin R, Hatfield AK, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med. 1994;330:592-596.
    2. Cleeland CS. Undertreatment of cancer pain in elderly patients. JAMA. 1998;279(23):1914-1915.
    3. Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):4040-4049.
    4. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, et al. Intrathecal drug delivery for the management of cancer pain: a multidisciplinary consensus of best clinical practices. J Support Oncol. 2005;3(6):399-408.
    5. Carr D, Goudas L, Lawrence D, et al. Management of cancer symptoms: pain, depression, and fatigue. Evidence Report/Technology Assessment No. 61 (Prepared by the New England Medical Center Evidence-based Practice Center under Contract No 290-97-0019). AHRQ Publication No. 02-E032. Rockville, MD: Agency for Healthcare Research and Quality. July 2002. Downloaded at http://archive.ahrq.gov/downloads/pub/evidence/pdf/cansymp/cansymp.pdf on 03/15/11.
    6. Bernabei R, Gambassi G, Lapane K, Landi F, et al. Management of pain in elderly patients with cancer. JAMA. 1998;279(23):1877-1882.
    7. Cleeland CS, Gonin R, Baez L, Loehrer P, Pandya K. Pain and pain treatment in minority outpatients with metastatic cancer. Ann Intern Med. 1997;127:813-816.
    8. Doleys DM, Olson K. eds. 2007. Psychological assessment and intervention in implantable pain therapies. Medtronic, Inc. Minneapolis, MN.

    Trial

    A trial is required to assess the effectiveness of intrathecal drug delivery as a treatment option for chronic intractable pain.

    A trial can be performed:1

    • Using epidural or intrathecal administration
    • Using a single bolus injection, multiple bolus injections, or continuous infusion
    • With or without an intraspinal catheter
    Trialing Overview
    View

    Dr. Wellington: Trialing Overview

    (0:49, 10.1 MB)

    Dr. Joshua Wellington describes his trialing method, including site of service, type of dosing, and opioid discontinuation.

    View more Approaches to Targeted Drug Delivery videos

    Route of Administration for the Trial

    Morphine can be delivered into either the epidural or intrathecal space of the spine. When the epidural route of administration is used, more time is required for the morphine to cross the dura and reach the dorsal horn in the spinal cord. 

    In contrast, intrathecal morphine binds with opiate receptors in the spinal cord without having to cross the dura. Therefore, intrathecal drug delivery results in faster analgesic action and requires significantly lower doses of morphine to produce the same degree of analgesia as epidural delivery.

    Existing clinical research data do not clearly indicate that one protocol is associated with a better outcome than others. Therefore, the benefits and risks of each possible choice must be weighed.1


    Assessing the Outcome of the Trial

    The following criteria may be used to assess the outcome of the intrathecal drug delivery trial: 

    • Pain Control – Did the trial relieve the patient’s pain?
    • Activities – Did the trial improve the patient’s ability to participate in daily living activities?
    • Medication – Did the need for oral pain medications change during the screening test?

    Refer to the Intrathecal Morphine for Pain Management chapter of the SynchroMed® II Infusion System Clinical Reference Guide of the for detailed information and procedures on the patient screening test for intrathecal drug delivery.

    References
    1. Follett KA, Doleys DM. Selection of Candidates for Intrathecal Drug Administration to Treat Chronic Pain: Considerations in Pre-Implantation Trials. Medtronic, Inc. Minneapolis, MN. 2002.

    Tools and Resources

    In the Intrathecal Morphine for Pain Management chapter of the SynchroMed® II Clinical Reference Guide there are several patient selection tools and resources:

    • Patient Education Checklist for Trial
      This detailed checklist of educational topics for use during patient selection for intrathecal drug delivery is found in the appendix of the guide.
    • Patient Selection Information
      Detailed information and procedures on patient selection is included in the Patient Selection and Trials section of the guide.
    • Patient Screening Test
      Detailed information for performing the patient screening test for intrathecal drug delivery is included in the Patient Selection and Trials section of the guide.

    Patient Selection Studies

    Polyanalgesic Consensus Conference-2012: Recommendations on Trialing for Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

    "Trialing for intrathecal pump placement is an essential part of the decision-making process in placing a permanent device. In both the United States and the international community, the proper method for trialing is ill defined."

    Deer TR, Prager J, Levy R, Burton A, et. al. Neuromodulation. 2012 Apr 11. doi: 10.1111/j.1525-1403.

    Prospective Study of 3-year Follow-up of Low-dose Intrathecal Opioids in the Management of Chronic Nonmalignant Pain

    "Long-term follow-up with the use of low-dose opioids in intrathecal (IT) drug delivery system (DDS) for the treatment of intractable, severe chronic nonmalignant pain."

    Pain Med. 2012 Oct;13(10):1304-13. doi: 10.1111/j.1526-4637.2012.01451.x. Epub 2012 Jul 30.

    Patient Selection and Outcomes Using a Low-dose Intrathecal Opioid Trialing Method for Chronic Nonmalignant Pain

    "The specific aim of the current study is to report results of patients trialed using a low-dose intrathecal morphine technique in the treatment of chronic noncancer pain."

    Pain Physician. 2011 Jul-Aug;14(4):343-51.

    Consensus Guidelines for the Selection and Implantation of Patients with Noncancer Pain for Intrathecal Drug Delivery

    "Using experience- and knowledge-based expert opinion to systematically evaluate the available evidence, this article provides consensus guidelines aimed at optimizing the selection of patients with noncancer pain for intrathecal therapy."

    Deer TR, Smith HS, Cousins M, et al. Pain Physician. 2010 May-Jun;13(3):E175-E213.

    United States