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Consensus on outcome measures for chronic pain trials
Pain 113 (2005) 1–2 www.elsevier.com/locate/pain
Editorial
Consensus on outcome measures for chronic pain trials I hope that readers will take the publication of the consensus meeting report by the IMMPACT group (the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials), published in this issue of Pain (pages 9–19), as the start of a debate. The report considers the core outcome measures for chronic pain trials, covering the core chronic pain outcome domains proposed by a previous IMMPACT meeting (Turk et al., 2003) as necessary in chronic pain research. The authors are to be congratulated for organising a forum at which these matters are discussed, with a mixture of clinical scientists, industry and regulatory people. The focus is North American. The authors have a web site at www.immpact.org, that gives details of the meetings and background papers. A consensus document emerges from each meeting and is published.
1. The meat The six core outcome domains recommended by the previous IMMPACT meeting for consideration in chronic pain clinical trial design were (Turk et al., 2003): (1) (2) (3) (4)
pain physical functioning emotional functioning participant ratings of improvement and satisfaction with treatment (5) symptoms and adverse events (6) participant disposition. The recommended outcome measures for these six domains are: (1) pain intensity rated on a 0–10 numerical rating scale, unless a well-accepted disease-specific measure of pain intensity is available; in addition, the amount of any rescue analgesics used (2) physical functioning assessed by the Multidimensional Pain Inventory Interference Scale or the Brief Pain Inventory pain interference items unless a well-accepted
(3) (4) (5) (6)
disease-specific measure of physical functioning is available emotional functioning assessed by the Beck Depression Inventory and the Profile of Mood States participant ratings of overall improvement assessed by the Patient Global Impression of Change scale adverse events using passive capture of spontaneously reported events and open-ended prompts participant disposition assessed in accord with CONSORT recommendations and including documentation of treatment adherence and reasons for premature withdrawal.
2. The beef Most of us involved in designing and doing clinical trials will already be trying (or should be) to measure these outcomes. It is the choice and recommendation of particular scales that causes the problem. On the one hand, if IMMPACT sits on the fence and makes no recommendation then all this becomes motherhood and apple pie. On the other hand by recommending particular scales, then those who use a different scale for a particular domain have to consider their position. Industry and regulatory bodies may welcome a proscriptive ‘this scale for this domain’ document. The academic question of whether or not this scale is indeed the best scale may be a secondary concern. A document that was not intended to be proscriptive may become so. Given that most drug research is financed by industry it might be naive to believe that there is no risk of stifling further debate and innovation. Hence the importance of encouraging you, the wider Pain audience, to respond and debate the recommendations. The actual evidence that one scale is ‘better’ than another for a particular domain is sparse. There are few if any clear winners. Most investigators have particular scales that they have always used, feel comfortable and confident with and do not want to change. The recommendations in this document have no particular force other than she or he who shouted loudest won the vote. As an example why pick the 0–10 numerical rating scale for pain intensity? The none,
0304-3959/$20.00 q 2004 Published by Elsevier B.V. on behalf of International Association for the Study of Pain. doi:10.1016/j.pain.2004.10.019
2
Editorial / Pain 113 (2005) 1–2
slight, moderate or severe categorical scale and the 100 mm visual analogue scale have worked well across acute and chronic pain studies for some decades. The reasoning in the paper about difficulty completing the various scales did not fit with our experience. The missing data problem will occur on any scale, and surely the problem lies in the way in which that is handled in the analysis, last observation carried forward or set pain intensity to baseline, rather than in the scale. The 0–10 numerical rating scale for pain intensity has of course been used successfully in a number of recent chronic pain drug studies, and I suspect that that is why it carried the day. But that is hardly an intellectually robust reason for recommending it over the others.
this discussion about outcome measures. To a degree what the US Food and Drug Administration decrees determines the trial design, including choice of outcome measures, which the pharmaceutical companies will seek to use around the world. Once again the authors need to be congratulated for organising this consensus meeting on outcome measures. The publication of their report is the opportunity to widen the debate and involve the many others around the world who have an interest in outcome measures for clinical studies in pain. If you do not debate the recommendations then you will be tacitly accepting them. If you disagree, then now is your chance to say so.
3. What’s the problem then? References There is not really a problem. There is a worry with a consensus meeting report published in a high impact (no pun intended) journal that these recommendations are accepted without any discussion. I think this is potentially dangerous when these recommendations are based on opinion rather than evidence. Consensus recommendations on breast cancer screening some years back were contentious and had to be ‘reconsidered’. An issue here is that as it becomes more difficult and expensive to do clinical trials in North America, our colleagues in other countries, with other languages, will be investigators, and need to be engaged in
*Tel.: C44 1865225404.
Turk DC, Dworkin RH, Allen RR, Bellamy N, Brandenburg N, Carr DB, Cleeland C, Dionne R, Farrar JT, Galer BS, Hewitt DJ, Jadad A, Katz NP, Kramer LD, Manning DC, McCormick CG, McDermott M, McGrath P, Quessy S, Rappaport BA, Robinson JP, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Witter J. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain 2003;106:337–45.
Henry McQuay* Department of Pain Relief, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK
Editorial
Consensus on outcome measures for chronic pain trials I hope that readers will take the publication of the consensus meeting report by the IMMPACT group (the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials), published in this issue of Pain (pages 9–19), as the start of a debate. The report considers the core outcome measures for chronic pain trials, covering the core chronic pain outcome domains proposed by a previous IMMPACT meeting (Turk et al., 2003) as necessary in chronic pain research. The authors are to be congratulated for organising a forum at which these matters are discussed, with a mixture of clinical scientists, industry and regulatory people. The focus is North American. The authors have a web site at www.immpact.org, that gives details of the meetings and background papers. A consensus document emerges from each meeting and is published.
1. The meat The six core outcome domains recommended by the previous IMMPACT meeting for consideration in chronic pain clinical trial design were (Turk et al., 2003): (1) (2) (3) (4)
pain physical functioning emotional functioning participant ratings of improvement and satisfaction with treatment (5) symptoms and adverse events (6) participant disposition. The recommended outcome measures for these six domains are: (1) pain intensity rated on a 0–10 numerical rating scale, unless a well-accepted disease-specific measure of pain intensity is available; in addition, the amount of any rescue analgesics used (2) physical functioning assessed by the Multidimensional Pain Inventory Interference Scale or the Brief Pain Inventory pain interference items unless a well-accepted
(3) (4) (5) (6)
disease-specific measure of physical functioning is available emotional functioning assessed by the Beck Depression Inventory and the Profile of Mood States participant ratings of overall improvement assessed by the Patient Global Impression of Change scale adverse events using passive capture of spontaneously reported events and open-ended prompts participant disposition assessed in accord with CONSORT recommendations and including documentation of treatment adherence and reasons for premature withdrawal.
2. The beef Most of us involved in designing and doing clinical trials will already be trying (or should be) to measure these outcomes. It is the choice and recommendation of particular scales that causes the problem. On the one hand, if IMMPACT sits on the fence and makes no recommendation then all this becomes motherhood and apple pie. On the other hand by recommending particular scales, then those who use a different scale for a particular domain have to consider their position. Industry and regulatory bodies may welcome a proscriptive ‘this scale for this domain’ document. The academic question of whether or not this scale is indeed the best scale may be a secondary concern. A document that was not intended to be proscriptive may become so. Given that most drug research is financed by industry it might be naive to believe that there is no risk of stifling further debate and innovation. Hence the importance of encouraging you, the wider Pain audience, to respond and debate the recommendations. The actual evidence that one scale is ‘better’ than another for a particular domain is sparse. There are few if any clear winners. Most investigators have particular scales that they have always used, feel comfortable and confident with and do not want to change. The recommendations in this document have no particular force other than she or he who shouted loudest won the vote. As an example why pick the 0–10 numerical rating scale for pain intensity? The none,
0304-3959/$20.00 q 2004 Published by Elsevier B.V. on behalf of International Association for the Study of Pain. doi:10.1016/j.pain.2004.10.019
2
Editorial / Pain 113 (2005) 1–2
slight, moderate or severe categorical scale and the 100 mm visual analogue scale have worked well across acute and chronic pain studies for some decades. The reasoning in the paper about difficulty completing the various scales did not fit with our experience. The missing data problem will occur on any scale, and surely the problem lies in the way in which that is handled in the analysis, last observation carried forward or set pain intensity to baseline, rather than in the scale. The 0–10 numerical rating scale for pain intensity has of course been used successfully in a number of recent chronic pain drug studies, and I suspect that that is why it carried the day. But that is hardly an intellectually robust reason for recommending it over the others.
this discussion about outcome measures. To a degree what the US Food and Drug Administration decrees determines the trial design, including choice of outcome measures, which the pharmaceutical companies will seek to use around the world. Once again the authors need to be congratulated for organising this consensus meeting on outcome measures. The publication of their report is the opportunity to widen the debate and involve the many others around the world who have an interest in outcome measures for clinical studies in pain. If you do not debate the recommendations then you will be tacitly accepting them. If you disagree, then now is your chance to say so.
3. What’s the problem then? References There is not really a problem. There is a worry with a consensus meeting report published in a high impact (no pun intended) journal that these recommendations are accepted without any discussion. I think this is potentially dangerous when these recommendations are based on opinion rather than evidence. Consensus recommendations on breast cancer screening some years back were contentious and had to be ‘reconsidered’. An issue here is that as it becomes more difficult and expensive to do clinical trials in North America, our colleagues in other countries, with other languages, will be investigators, and need to be engaged in
*Tel.: C44 1865225404.
Turk DC, Dworkin RH, Allen RR, Bellamy N, Brandenburg N, Carr DB, Cleeland C, Dionne R, Farrar JT, Galer BS, Hewitt DJ, Jadad A, Katz NP, Kramer LD, Manning DC, McCormick CG, McDermott M, McGrath P, Quessy S, Rappaport BA, Robinson JP, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Witter J. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain 2003;106:337–45.
Henry McQuay* Department of Pain Relief, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK