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Oxford league table of analgesics in acute pain

This league table was constructed for analgesics in acute pain. Information was from systematic reviews of randomised, double-blind, single-dose studies in patients with moderate to severe pain. For each review the outcome was identical - that is at least 50% pain relief over 4-6 hours. The pain measurements were standardised, and have been validated.

The league table works because it only has apples, and is not a fruit salad. Only like is compared with like, and there is a common comparator throughout, namely placebo. Information is presented in a number of formats, but the definitive source is the full Table , which has the number of patients in the comparison, the percent with at least 50% pain relief with analgesic, the number-needed-to-treat (NNT) and the high and low 95% confidence interval. This Table will be updated as more information becomes available. PDF versions of the FULL league table and of the TRUNCATED version are available following updating in 2007. There is also a listing for oral COMBINATION analgesics.

Much of the information is about drugs or doses not commonly used, and which is therefore of academic interest only. Figure 1 shows the NNTs for a number of common drugs and doses. The details are in Table 1, with links to the full reviews.

Figure 1: 2007 League table of number needed to treat (NNT) for at least 50% pain relief over 4-6 hours in patients with moderate to severe pain, all oral analgesics except IM morphine




Table 1: The Oxford league table of analgesic efficacy (commonly used and newer analgesic doses)

The 2007 Oxford league table of analgesic efficacy
(at least 3 trials or 200 patients)
Numbers needed to treat are calculated for the proportion of patients with at least 50% pain relief over 4-6 hours compared with placebo in randomised, double-blind, single-dose studies in patients with moderate to severe pain. Drugs were oral, unless specified, and doses are milligrams. Shaded rows are intramuscular administration
Analgesic and dose (mg) Number of patients in comparison Percent with at least 50% pain relief NNT Lower confidence interval Higher confidence interval
Etoricoxib 180/240
248
77
1.5
1.3
1.7
Etoricoxib 120
500
70
1.6
1.5
1.8
Diclofenac 100
545
69
1.8
1.6
2.1
Celecoxib 400
298
52
2.1
1.8
2.5
Paracetamol 1000 + Codeine 60
197
57
2.2
1.7
2.9
Rofecoxib 50
675
54
2.3
2.0
2.6
Aspirin 1200
279
61
2.4
1.9
3.2
Ibuprofen 400
5456
55
2.5
2.4
2.7
Oxycodone IR 10 + Paracetamol 650
315
66
2.6
2.0
3.5
Diclofenac 25
502
53
2.6
2.2
3.3
Ketorolac 10
790
50
2.6
2.3
3.1
Naproxen 400/440
197
51
2.7
2.1
4.0
Piroxicam 20
280
63
2.7
2.1
3.8
Lumiracoxib 400
370
48
2.7
2.2
3.5
Naproxen 500/550
784
52
2.7
2.3
3.3
Diclofenac 50
1296
57
2.7
2.4
3.1
Ibuprofen 200
3248
48
2.7
2.5
2.9
Pethidine 100 (intramuscular)
364
54
2.9
2.3
3.9
Tramadol 150
561
48
2.9
2.4
3.6
Morphine 10 (intramuscular)
946
50
2.9
2.6
3.6
Naproxen 200/220
202
45
3.4
2.4
5.8
Ketorolac 30 (intramuscular)
359
53
3.4
2.5
4.9
Paracetamol 500
561
61
3.5
2.2
13.3
Celecoxib 200
805
40
3.5
2.9
4.4
Ibuprofen 100
495
36
3.7
2.9
4.9
Paracetamol 1000
2759
46
3.8
3.4
4.4
Paracetamol 600/650 + Codeine 60
1123
42
4.2
3.4
5.3
Paracetamol 650 + Dextropropoxyphene (65 mg hydrochloride or 100 mg napsylate)
963
38
4.4
3.5
5.6
Aspirin 600/650
5061
38
4.4
4.0
4.9
Paracetamol 600/650
1886
38
4.6
3.9
5.5
Ibuprofen 50
316
32
4.7
3.3
8.0
Tramadol 100
882
30
4.8
3.8
6.1
Tramadol 75
563
32
5.3
3.9
8.2
Aspirin 650 + Codeine 60
598
25
5.3
4.1
7.4
Paracetamol 300 + Codeine 30
379
26
5.7
4.0
9.8
Tramadol 50
770
19
8.3
6.0
13.0
Codeine 60
1305
15
16.7
11.0
48.0
Placebo
>10,000
18
N/A
N/A
N/A

 


Understanding the league table

Effective relief can be achieved with oral non-opioids and non-steroidal anti-inflammatory drugs. Analgesic efficacy is expressed as the NNT, the number of patients who need to receive the active drug for one to achieve at least 50% relief of pain compared with placebo over a 4-6 hour treatment period. The most effective drugs have a low NNT of just over 2. This means that for every two patients who receive the drug one patient will get at least 50% relief because of the treatment (the other patient may or may not obtain relief but it does not reach the 50% level).

The NNT is treatment-specific, which is useful for comparison of relative efficacy. Because these NNT comparisons are against placebo, the best NNT of 2 means that 50 of 100 patients will get at least 50% relief specifically because of the treatment. Another twenty will have a placebo response giving them at least 50% relief. With ibuprofen 400 mg, therefore, about 70 of 100 in total will have effective pain relief. For comparison, with 10 mg intramuscular morphine about 53% of patients get more than 50% pain relief. Because the effect of placebo is added in, the comparisons between analgesics are not as stark as with NNT.

It is clear that the oral NSAIDs do extremely well in this single-dose postoperative comparison. At these doses they all have NNT values of between 2 and 3, and the point estimate of the mean is below that of (i.e. better than) 10 mg of intramuscular morphine, even though the confidence intervals overlap. The simple analgesics, aspirin and paracetamol are significantly less effective than 10 mg intramuscular morphine. The point estimates of the NNT are higher, and there is no overlap of the confidence intervals. Weak opioids perform poorly in single doses on their own. Combining them with simple analgesics improves analgesic efficacy.

Drawbacks of the league table

The most important drawback is size. Small trials (or small data sets) cannot accurately estimate the magnitude of the analgesic effect. To know that the NNT of an analgesic is 3.0 with a confidence interval of 2.5 to 3.5 we need almost 1000 patients in a comparative trial. So as you contemplate the numbers, be conscious of the amount of information upon which NNTs and percent of patients with at least 50% pain relief are based. In practice any comparison with more than 250 or so patients is probably adequate.

For instance, ibuprofen 800 mg is at the top of the league, with an NNT of 1.6 and with 100% of patients achieving at least 50% pain relief. But only 76 patients have ever been involved in comparative trials with placebo. This makes the apparent wonderful result less so, and you should treat it cautiously.

The information is presented here, warts and all, so that professionals and public can make their own assessments.

What is missing?

Adverse effects from single-dose analgesic trials are rarely helpful with simple analgesics and NSAIDs, though they may be much more helpful with opioids. Work on adverse effects is being done, and a summary of this will appear on this site later in 1999.

Some analgesics used commonly outside the UK may not be represented. Again work is ongoing to plug these gaps, but so often the randomised trials (placebo-controlled, randomised, double-blind and with proper outcome measures and entry criteria), have not been done.

Finally cost information is not given here, because it can vary so much throughout the world.