Study design and subjects

We conducted a randomised, controlled trial with blinded evaluation and statistical analysis of results. It was carried out at the pain management unit in a public primary care centre in southern Spain, over a period of two years. The unit caters for the population of three primary care centres (75 000 inhabitants).

All the doctors at the three health centres in the study area received information about the study and inclusion criteria. We also informed them about the procedure for referring patients to the pain management unit, to be included in the selection process, and requested their collaboration in selecting patients to take part. Such patients were outpatients in whom osteoarthritis of the knee had been clinically and radiologically diagnosed according to the criteria of the American College of Rheumatology.6 The illness had to be symptomatic at the moment of selection. All patients gave their informed consent before taking part in the study.

The pain management unit applied the following criteria for inclusion in the study: patients had to be aged 45 years or older, with pain in one or both knees for the preceding three months or longer, and with radiological evidence of osteoarthritis of the knee (at least grade 1 according to the Ahlbäck classification,7 table 1). They had to be outpatients and willing and able to complete the study questionnaire. Criteria for exclusion were previous treatment with acupuncture; contraindication to medication with diclofenac; inflammatory, metabolic, or neuropathic arthropathies; severe concomitant illnesses that might interfere with the clinical evaluation of the patient; severe or generalised dermopathy; pregnancy or existing treatment with antineoplasic, corticoid, or immunosuppressive drugs.

The patients were divided into two groups, an intervention group treated with acupuncture plus diclofenac and a control group given placebo acupuncture plus diclofenac. We used a computer program to assign the patients randomly to one or the other group8; the invention group comprised 48 participants and the control group 49. We used a simple random allocation method. We sent out sealed opaque envelopes. Only the doctor applying the treatment was aware which group each patient had been assigned to, and he did not participate in any phase of the subsequent evaluation. We took precautions to maintain the confidentiality of the data concerning the participating patients. Before starting treatment, all patients observed a one week period during which they did not take any NSAIDs.

Treatment applied

True and placebo acupuncture

A doctor specialising in acupuncture (accredited by the Beijing University of Medical Sciences (China) and by the Scientific Society of Medical Acupuncture (ACMAS Huangdi, Spain)) selected acupuncture points on the basis of traditional treatment methods found to be effective for osteoarthritis of the knee.9 10 The standard acupuncture intervention entailed the insertion of sterile, single use, 30 gauge, and 45 mm length acupuncture needles into the local points GB34, SP9, EX-LE5, and ST36 (fig 1). The distal points were KI3, SP6, LI4, ST40. For each of the points in question the acupuncturist determined the patient's sensation of Deqi (an elicitation of needle sensation to check that the puncture was performed in the correct site). A WQ-10D1 electrostimulator was used to stimulate all the needles inserted into the local points electrically, in pairs. The treatment lasted 12 weeks, starting with visit 0 and ending with visit 11. The doctor carried out the final evaluation at visit 12, one week after the treatment had ended.

View larger version:

• In a new window

• Download as PowerPoint Slide

Fig 1

Location of selected acupuncture points

The same specialist carried out the placebo acupuncture, at the same frequency and for the same duration as for the group receiving the true intervention. Retractable needles went into small adhesive cylinders, such that the needle was supported but did not perforate the skin.11 The acupuncturist then placed the needles over the same points as were used for the true acupuncture group. He connected the same pairs of electrodes and simulated the electrical connection.

Statistical analysis

We used a freeware program14 to calculate the sample size for a mean total WOMAC score of 20 (SD 10) for the intervention group and of 33 (SD 28) for the control group, with bilateral contrast, a significance level of 0.05, and a power of 0.80. The minimum sampling size was 69. Assuming a maximum dropout rate of 20% we increased the minimum sample size to 83 patients. We selected 97 patients (fig 2).

View larger version:

• In a new window

• Download as PowerPoint Slide

Fig 2

Flow of participants through the trial

We performed a baseline analysis of the two groups to seek clinically relevant differences, considering sociodemographics, severity of illness, and result. For the dropout analysis we used the Mann-Whitney U test for independent samples, together with Fisher's exact statistic (table 2).

We used SPSS, version 11.5, to analyse the results by intention to treat, on the basis of the improvement in the total WOMAC score, on the pain visual analogue scale, and the PQLC score, using Student's t test for independent samples. We set P < 0.05 as the significance level for all the tests. For patients who withdrew, the score we used for each variable was the worst of the scores obtained for the intervention group and the best obtained for the control group. When a diagnosis of bilateral osteoarthritis of the knee had been made, the knee with the worse results at baseline was the knee we evaluated in the final analysis.

Mean results

Acupuncture as a complementary therapy to pharmacological treatment of osteoarthritis of the knee is more effective than pharmacological treatment alone, in terms of reducing pain and rigidity, and improving physical functioning and health related quality of life.

According to the criterion that an improvement in quality of life requires changes in at least two of the variables measured by the PQLC, the acupuncture provided to the intervention group was more effective than the placebo treatment in improving patients' quality of life.

True and placebo acupuncture

We decided to use a technique in the control group that did not require transcutaneous penetration, thus avoiding neurophysiological and neurochemical responses owing to the stimulation of cutaneous receptors; the intervention and control groups received treatments that were apparently identical: real acupuncture plus medication versus placebo acupuncture plus medication. By supplying both groups with medication, we sought to overcome possible ethical objections related to the role of the control group in the study.

Blinding procedure

Although the standard treatment was given for 12 weeks, participants who dropped out of the study were mainly from the control group, and only six people were lost to the study because their condition did not improve. To reinforce the blinding of the groups we expanded the criteria for selection of study patients to include the requirement that they should not have received previous acupuncture treatment; none of the participants lost to the study made any reference to belonging to one or the other of the two groups. Both the evaluation of the results and the statistical analysis were carried out in a blind fashion. These factors reinforce our belief that the blinding procedure applied was successful.

Limitations of the study

Observation of the sample groups over a period of 12 weeks may be insufficient to evaluate the effects of treatment in the medium term. Moreover, we did not test the patients' awareness of belonging to one or the other group, and so their complete “blindness” cannot be assured. Another possible limitation was the absence of techniques to verify the behaviour of the therapist, although the time spent with each patient was recorded; this was always close to the mean value (29.4 minutes).

Taking into account the duration of the study (12 weeks), we recorded patients' body mass index at the beginning and the end of the study, to evaluate the possible confounding effect of weight loss or gain. We found no significant differences.

We used different measurement techniques to evaluate the results obtained, testing whether the changes were all in the same direction and checking the consistency of the efficacy end points. We decided to use the categorical version of the WOMAC index because of the low cultural level of the population in the study area, and Spain's index of quality of life (PQLC) as a valid test for chronically ill patients. We considered the “total accumulated consumption of diclofenac” an objective variable with which to measure the responses of the two sample groups. As osteoarthritis is still an incurable illness, treatment is fundamentally aimed at improving the patient's quality of life, which is why we included this variable in the study. The consistency of the results is endorsed by the fact that the different aspects of physical functioning improved, according to both indices, the WOMAC and the PQLC. It is noteworthy that the evaluators were unaware of the group to which the patient had been assigned.

Comparison with other studies and outlook

The studies published to date have methodological deficiencies in the description and application of the method chosen for randomisation, the concealment of the treatment assignation scheme, the homogeneity of the groups to be compared, the control of co-interventions, the lack of control over participants' compliance with medical instructions, and the “blinding” of patients and evaluators; and the heterogeneity of follow up periods was high.15^–18 We attempted to improve on the methodological design of previous work, using a controlled, single blind, randomised trial with evaluation and analysis by third parties; the sample size was appropriate, and we controlled for possible confounding factors to a suitable degree; the professionals involved were suitably qualified; the placebo was adequately chosen; and the quality control of the materials used was ensured. We put particular emphasis on ascertaining the patient's sensation of Deqi when acupuncture was applied, and on describing secondary effects and the success of the technique in improving the patient's quality of life (PQLC).

Similar results were found in a small, short term and long term study, carried out by using the waiting list as the control group,15 and in another study that compared acupuncture plus baseline treatment with baseline treatment alone.16 In these studies, the absence of a placebo was a serious limitation to the validity of the conclusions; a third study incorporated a placebo, but in a hospital environment considered to be of low quality,5 whereas treatment was of greater intensity and duration of treatment was shorter.17 Another study compared acupuncture with sham acupuncture and found no statistically significant differences.18

Future research should extend the observation period after treatment in order to evaluate the duration of the improvement obtained and to establish treatment protocols.