Intended for healthcare professionals


Topical NSAIDs are better than placebo

BMJ 1998; 317 doi: (Published 25 July 1998) Cite this as: BMJ 1998;317:280

Safety, efficacy, and therapeutic role of NSAIDs must be clarified

  1. Martin Duerden, Assistant medical director,
  2. Stuart Barton, Medical director,
  3. Elaine Johnstone, Senior pharmacist, MeReC Publications,
  4. Kirsty MacLean, Pharmacist, MeReC Publications,
  5. Jonathan Underhill, Pharmacist, MeReC Publications,
  6. Tom Walley, Professor of pharmacology and therapeutics
  1. National Prescribing Centre, The Infirmary, Liverpool L69 3GF
  2. University of Liverpool, Liverpool L69 3GF
  3. University of Oxford, Pain Relief Unit, Churchill Hospital, Oxford OX3 7LJ

    EDITOR—Moore et al concluded in their study that topical non-steroidal anti-inflammatory drugs are better than placebo in acute and chronic musculoskeletal pain.1Does this help to define their role in practice?

    While we accept that these agents are better than placebo (this is considered during drug licensing), this does not help to decide how clinically effective they are. To definea therapeutic role for these preparations2we need comparisons with other interventions, such as oral non-steroidal anti-inflammatory drugs, topical rubefacients, or paracetamol. Of the 87 trials reviewed by Moore et al only five compared topical with oral non-steroidal anti-inflammatory drugs, and none had adequate design or power to enable comparison.

    We are also concerned about the methodology used in this review. Moore et al conclude that the trials reviewed were of a good quality. We recently reviewed this area and found that many trials had poor methodology, low numbers of patients, and short durations of treatment.3The quality analysis used by Moore et al is simplistic and may not fully evaluate the quality of the studies. We do, however, recognise the need to use some objective quantification of quality.

    Secondly, combining results from different studies of patients with varied musculoskeletal conditions may introduce errors, and a reliable meta-analysis of these agents could be difficult.4One of the reasons for this is that the heterogeneity of conditions being studied makes it difficult to compare one study with another. We are not sure whether using the random effects model compensates sufficiently.

    Thirdly, the authors were unable to eliminate positive publication bias. As drug companies were asked to volunteer their trial data, this bias may extend to unpublished studies. The small number of trials volunteered by drug companies reinforces this concern.

    While the authors concede that further comparisons of topical with oral non-steroidal anti-inflammatory drugs are required, their conclusion that topical agents are effective and safe is not supported by their paper. Furthermore, it gives no guidance on when these drugs should be used. Not only may this review give the wrong messages to prescribers but it may be used inappropriately to promote non-evidence based prescribing. Until data are published that compare these agents with other alternatives—such as paracetamol, other much cheaper rubefacients, and interventions such as rest, ice, compression, and elevation—their therapeutic role remains unclear. Without this evidence it is difficult to justify a large proportion of the £33 million spent on these drugs over the past year (Prescription Pricing Authority, data on file, Oct 1997).


    Authors' reply

    1. R A Moore, Consultant biochemist.,
    2. M R Tramer, Research fellow,
    3. D Carroll, Senior research nurse,
    4. P J Wiffen, Regional pharmaceutical adviser.,
    5. H J McQuay, Clinical reader in pain relief
    1. National Prescribing Centre, The Infirmary, Liverpool L69 3GF
    2. University of Liverpool, Liverpool L69 3GF
    3. University of Oxford, Pain Relief Unit, Churchill Hospital, Oxford OX3 7LJ

      EDITOR—Duerden et al at the National Prescribing Centre reject our findings on topical non-steroidal anti-inflammatory drugs. In August 1997 their MeReC Bulletin concluded that “this high level of prescribing [of topical non-steroidal anti-inflammatory drugs] is still not justified.” That conclusion was not based on a systematic review of literature, explicit inclusion and exclusion criteria, or explicit existing definitions of efficacy of treatment. Our review was.

      Duerden et al confuse two issues—namely, whether topical non-steroidal anti-inflammatory drugs work and whether prescribing them is appropriate. On the basis of information from over 10 000 patients we can say that these drugs work. There is no evidence thatpain from different acute injuries or chronic rheumatic conditions reacts differently to different treatments. If we kept splitting studies by condition of pain, sex, race, or some other variable, then our knowledge would be relevant for ever smaller groups of patients.

      The credibility of MeReC's advice on the appropriateness of prescribing will be diminished if that advice is perceived to be driven by cost rather than by evidence. Duerden et al ask for topical non-steroidal anti-inflammatory drugs to be compared with other (cheaper) rubefacients and rest. At the moment the evidence is stronger for topical non-steroidal anti-inflammatory drugs. We could find no recent trials of rubefacients or rest, ice, compression, and elevation. The literature on oral paracetamol in arthritic pain is sparse.

      It is not our responsibility as reviewers to provide advice on prescribing. Those whose responsibility it is need to be scrupulously careful about the evidence they use in formulating their advice. Duerden et al disparage our review by claiming (wrongly) that it offends against rules of evidence. At the same time they are prepared to recommend (cheaper) alternatives for which there is little, if any, evidence.

      We have reviewed the world's literature on topical non-steroidal anti-inflammatory drugs; comparisons with paracetamol or rest, ice, compression, and elevation do not exist. That helps to define a research agenda. In the meantime, prescribing advisers should avoid taking pot shots at the messenger just because they don't like the message.

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