Edler-Buggy S, Birtwistle J, ElMokhallalati Y, et al. Regular dosing compared with as-needed dosing of opioids for management of chronic cancer pain: systematic review and meta-analysis. Pain. 2020 Apr;161(4):703-712. doi: 10.1097/j.pain.0000000000001755. (Systematic review)

Opioids are the recommended form of analgesia for patients with persistent cancer pain, and regular dosing "by the clock" is advocated in many international guidelines on cancer pain management. The development of sustained-release opioid preparations has made regular dosing easier for patients. However, patients report that the intensity and impact of their cancer pain varies considerably day to day, and many try to find a trade-off between acceptable pain control and impact of cognitive (and other) adverse effects on daily activities. In acute care settings, (eg, postoperative) as-needed dosing and other opioid-sparing approaches have resulted in better patient outcomes compared with regular dosing. The aim of this study was to determine whether regular dosing of opioids was superior to as-needed dosing for persistent cancer pain. We systematically searched for randomised controlled trials that directly compared pain outcomes from regular dosing of opioids with as-needed dosing in adult cancer patients. We identified 4347 records, 25 randomised controlled trials meet the inclusion criteria, 9 were included in the review, and 7 of these included in meta-analysis. We found no clear evidence demonstrating superiority of regular dosing of opioids compared with as-needed dosing in persistent cancer pain, and regular dosing was associated with significantly higher total opioid doses. There was, however, a paucity of trials directly answering this question, and low-quality evidence limits the conclusions that can be drawn. It is clear that further high-quality clinical trials are needed to answer this question and to guide clinical practice.

Discipline Area Score
Physician 6 / 7
Comments from MORE raters

Physician rater

This is an important question for which data needs to be collected. The authors point out the current data does not answer this question. There is also the question of which method of dosing (and the volume of opiates prescribed) is safer from a public health point of view.

Physician rater

This provocative meta-analysis brings forward a therapeutic option that is often already used. However, the data are not conclusive due to the heterogeinity of results and small sample size. Either more well planned and adequately powered trials are run or perhaps individualization of treatment options, as suggested by the authors will remain paramount.

Physician rater

This study seeks to answer a very important question in the palliative care of patients with cancer: how should we approach opioid administration? I come from Asia and here we tend to use these drugs sparingly if possible. In other places it may be used more frequently and earlier on. The results of this meta-analysis only confirm what we already know from our varied clinical experiences - either approach can work. If one favors a reduction in opioid adverse effects then a prn strategy may be the way to go. However pain is a complicated clinical phenomenon and two patients with the exact same pathology may experience the ‘same’ pain differently; thus requiring different strategies to control - one may experience relief with as needed opioids while the other may require a regular (RTC) schedule. There is simply no one-size-fits-all approach to this in my view.
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