Smith, T.J., & Coyne, P.J. (2005). Implantable drug delivery systems (IDDS) after failure of comprehensive medical management (CMM) can palliate symptoms in the most refractory cancer pain patients. Journal of Palliative Medicine, 8, 736–742.

To evaluate whether implantable drug delivery systems (IDDS) could help the most refractory patients failed by expert comprehensive medical management (CMM)

This was an RCT of IDDS (starting with morphine, but changing to a different drug if ineffective) plus CMM versus CMM alone in 200 patients with refractory cancer pain. Patients were randomized to CMM or IDDS. Clinical success was defined as a 20% reduction of pain regardless of toxicity or a 20% reduction of toxicity without a resulting increase in pain. A more stringent measure was a 20% reduction in both pain and toxicity. Results were obtained from weeks 4 and 12.

• N = 99 patients in the group (66 CMM only, 30 CMM plus IDDS)
• AGE: CMM only = 44–72 years; CMM plus IDDS = 32–69 years
• MALES: CMM only = 62.3 % males; CMM plus IDDS = 53.3% male
• KEY DISEASE CHARACTERISTICS: Patients had cancer. Cancers include lung, breast, prostate, colon, and pancreas.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had a visual analog scale (VAS) score of 5 or more despite pain management, were taking at least 200 mg oral morphine or equivalent, and had at least three months to live.

• RCT with crossover for clinical failure (pain 5 or more, limiting side effects, approved by investigator)

• VAS and National Cancer Institute Cancer Therapy Evaluation Program (CTEP) scales
• Composite drug toxicity score
• CMM measured by “Management of cancer pain: A quick reference guide for clinicians” (Agency for Health Care Policy and Research, 1994)

CMM patients who crossed to IDDS for the most refractory pain had a significant reduction in pain and drug toxicity. Patients who failed CMM and crossed to IDDS had a 27% reduction in pain scores and a 51% reduction in toxicity. Patients who failed CMM had a 20% reduction in pain, but pain was moderate to severe, while their opioid toxicity increased by 22%. Survival was improved in patients who received IDDS much earlier. Side effects and complications of IDDS were minimal, and there were no pump removals or infections.

Even the most refractory patients can have clinically important reductions in pain scores and drug side effects by crossing to IDDS. IDDS are shown to be comparable to other high-cost but effective cancer interventions. With refractory pain, the addition of IDDS to CMM can significantly improve pain management. A survival time of three months may be long enough for IDDS implant to be cost-effective.

• Small number of patients
• Question if improvement could be related to patients changing therapy when symptoms worsened, the Hawthorne effect, or placebo effect (implantation of a technological advanced device)
• Results may not be applicable to other centers with less experienced CMM or IDDS.

Studies need to look at the reason for improved survival with better pain control.