In evidence-based medicine, randomized controlled trials (RCTs) are the preferred method for evaluating the efficacy of interventions. In regard to acupuncture RCTs, the most difficult issues are the design of the control group and implementation of the principle of “double-blinding.” We compared the advantages and limitations associated with different control group designs in acupuncture RCTs, to assist researchers in this field.
Acupuncture is a convenient, effective, and simple form of traditional Chinese medicine that has few side effects [
Evidence-based medicine (EBM) [
The ongoing debate about the therapeutic effects of acupuncture for some diseases [
One researcher [
The purpose of this study was to systematically review the construction of control groups in RCT acupuncture studies published over the last few decades.
A literature search was performed using the PubMed English language database, using the search keywords “acupuncture” and “placebo needle.” We included studies that met the following criteria: randomized control trials (RCTs) that adopted a double-blind, single-blind, or nonblind design. We chose studies that we considered to be representative for each category of control group design. We focus our analysis on the design of control groups in acupuncture studies, instead of evaluating the efficacy of acupuncture in each study.
A survey of the literature reveals that 11 different designs exist for control groups in acupuncture RCTs, as shown in Table
Acupuncture study control group designs.
Number | Categories | Method | Purpose | Advantage | Limitation |
---|---|---|---|---|---|
(1) | Nontreatment contrast | CG: not receiving any treatment; TG: acupuncture [ |
To assess the effects of acupuncture | Observe the progression of the condition and patient recovery | No blinding; placebo effects of acupuncture are not eliminated. |
(2) | Complementary contrast | CG: standard western medicine (with [ |
To compare the effects of western medicine and western medicine plus acupuncture | Clarify the costs and side effects of acupuncture as the complementary therapy | Blinding is inadequate unless placebo acupuncture is used. |
(3) | Alternative contrast | CG: standard western medicine; |
To compare the effects of acupuncture and western medicine | Demonstrate the effectiveness of acupuncture as the alternative therapy and assess the costs and side effects | No blinding; placebo effects of acupuncture are not eliminated, resulting in the |
(4) | Nonacupuncture contrast | CG: nonpenetrating intervention, for example, TENS or laser acupuncture; |
To assess the different effects of acupuncture, TENS, and laser acupuncture | Similar amounts of time and attention are spent on each group, thereby helping to eliminate some of the placebo effect | It is impossible to ensure blinding because of the substantial differences between the CG intervention and acupuncture. |
(5) | No effects of nonacupuncture contrast | CG: mock nonpenetrating intervention, for example mock-TENS or mock laser acupuncture; |
To observe whether the therapeutic effects of acupuncture are greater than those of a nonpenetrating placebo intervention | If the TG receives TENS or laser acupuncture, elimination of the placebo effect and blinding can be assured. |
It is impossible to ensure blinding because of the substantial differences between the CG intervention and acupuncture |
(6) | Sham acupuncture contrast | CG: insertion points are not acupoints or meridians; |
To compare the effects of acupoints with sham points | The needling methods are the same in the CG and TG, resulting in an optimal elimination of placebo effect, and blinding can be performed | The effects of acupuncture on pain are underestimated. |
(7) | Nonspecific sites contrast | CG: acupuncture at acupoints which are considered to produce no or only minor effects; |
To compare the specific effects of acupuncture points | Needling methods are the same in the CG and TG, resulting in an optimal elimination of placebo effect, and blinding can be performed | The effects of acupuncture on pain are underestimated. |
(8) | Minimal acupuncture contrast* | CG: insertion points are not acupoints, and needle penetration is to a depth of less than 4 mm; |
To assess the effects of acupuncture at acupoints with manipulating stimulation | The elimination of placebo effect, blinding is ensured; the procedure is easily manipulated | Potential therapeutic effects in the control group. To increase the efficacy of blinding, acupuncturists decreased the manipulation in the TG which then reduced the effects and confounded the results, and analysis. “De-chi” was not attained |
(9) | Superficial acupuncture contrast | CG: dull needles or other tools (e.g., needle tube, toothpicks) are slapped on acupoints and tapped on them; dull needles do not prick the skin; |
To examine whether acupuncture is more effective than placebo acupuncture | The physiological reaction in the control group is minimal; the procedure is easily manipulated and suitably applied without requiring a novel study design; the blinding is effective | The operating locations were restricted to areas patients could not see, such as the neck, upper back, and dorsal side of limbs. The sensation was minimal and “de-chi” was not attained, which influenced the blinding for patients with previous experience of acupuncture; thus, the protocol cannot be used in long-term research |
(10) | Placebo needle contrast | CG: Streitberger’s needle, Park Sham Device, or Takakura’s needle with a blunt tip was tapped onto the skin; |
To observe whether real acupuncture is more effective than placebo acupuncture | The placebo effect and blinding are regarded as optimal, and, thus, the protocol has been widely used with good confidence | The major limitation of placebo needles is the associated lack of the “de-chi” sensation. Certain body sites cannot undergo acupuncture with these devices, such as the fingers, toes, and scalp, as well as sites that require transverse insertion or oblique insertion. |
(11) | Combined multiple methods contrast | ||||
(a) | CG: medicine and acupuncture placebo; TG: acupuncture and placebo medicine [ |
To reduce the psychological influence | The blinding and elimination of placebo effects were enforced to contrast the specific therapeutic effects between acupuncture and medicine | The procedure is difficult to use in long-term research | |
(b) | CG: placebo needles inserted into acupoints and real needles inserted into sham points; |
To produce similar therapeutic experience in the 2 groups; promote blinding and eliminate placebo effects | Blinding was effective, and the nonspecific effect of placebo needles was reduced | Participants with previous acupuncture experience may be conscious of the difference in acupoint site(s), which affects the blinding |
CG: Control group; TG: Test group; TENS: Transcutaneous electrical nerve stimulation; *Minimal acupuncture was termed superficial acupuncture in some studies [
The purpose of the control group is to determine the effect of the intervention by properly eliminating any placebo effect produced by the test group. Therefore, RCT study designs must include at least 1 control group. Importantly, the control group must experience the same placebo effect as the test group, and ideally participants and researchers are blinded as to whether participants receive treatment or placebo.
An ideal acupuncture control group must include three conditions. First, the design should be accepted by the study subjects, who must be blinded as to their assigned treatment group. Second, the curative effects should be minor and not give rise to special therapeutic effects that influence the results. Third, all other conditions for controls, excluding the intervention, should be identical to those used for the test group.
Four different strategies for designing control groups have been used alone or in combination in recent acupuncture RCTs: (1) absence of acupuncture needle insertion, (2) different location of inserted acupuncture needles, (3) different depth of insertion, and (4) the use of assistant tools. In regard to the absence of acupuncture needle insertion, the control group employed an imitative puncture action and no acupuncture, performed at specific acupoints, nonspecific acupoints, or sham acupoints. In regard to different locations for inserted acupuncture needles, specific acupoints consisted of the acupoints applied in the test group according to the meridian method of acupuncture, while sham acupoints comprised the points drifting off the specific acupoints or meridian above 0.5 B-cun and not on the meridian or known acupoints. However, the optimal distance for drifting off the specific acupoints or meridian remains controversial. Nonspecific acupoints are acupoints with nontherapeutic effects or minor effects that have been observed in previous research. In regard to different depth of insertion, needle insertion depths are categorized as superficial, minimal, or deep acupuncture. Superficial acupuncture does not pierce the epidermis. In minimal acupuncture, the needle penetrates to a depth of less than 4 mm and does not cause “de-chi.” Deep acupuncture involves needle passage through the hypodermis to a depth of more than 5 mm, usually 10–20 mm, and often causes “de-chi.” In reference to the use of assistant tools, placebo needles [
Laser acupuncture and TENS usually serve as nonacupuncture contrasts, meaning that they are not involved in needle insertion. Laser acupuncture has been clinically applied since the 1970s [
TENS is a noninvasive analgesic technique that is usually used to relieve nociceptive, neuropathic, and musculoskeletal pain [
Because of these possible therapeutic effects, using TENS as the control group intervention may cause underestimation of acupuncture effects. Moreover, the procedure of TENS differs from acupuncture. Therefore, blinding is impossible. It is noted that TENS should not be applied on the anterior and posterior areas of the chest because TENS may compromise pulmonary ventilation due to the stimulation of the intercostal muscles [
Needle pricking may induce nonspecific physiological reactions and diffuse noxious inhibitory controls (DNICs) [
Minimal acupuncture requires that insertion points are not acupoints and needle penetration is to a depth of less than 4 mm, while superficial acupuncture requires that dull needles or other tools (e.g., needle tube and toothpicks) are tapped onto acupoints; dull needles do not prick the skin. It was assumed that both interventions have no therapeutic effects. However, recent studies did not agree with this assumption. Lightly touching the skin stimulates mechanoreceptors coupled to slow conducting unmyelinated C afferents that causes activity in the insular region, but not in the somatosensory cortex [
Nonspecific acupuncture involves acupuncture performed at acupoints that are considered to produce only minor or no effects. However, care must be taken as to choice of nonspecific acupoints: inappropriate selection will render the study invalid. Not only does it remain controversial as to the optimal distance for drifting off specific acupoints or meridian when using sham acupuncture, but also, if two meridians are sited closely together, the sham acupoints may be located on an unintended meridian. For long-term study, both nonspecific and sham acupuncture are considered to be more appropriate as control interventions because they involve real needle insertion.
Placebo needling is considered to be a credible technique for use in subjects with little or no experience of acupuncture [
We list 11 different designs and four strategies associated with control group design in acupuncture RCTs. In clinical practice experience, efficacy is closely related to the manipulation of acupuncture performance, including the lifting and thrusting of needles or needle rotation. For example, in acupuncture analgesia, stronger stimulation (rotating needles with higher frequency and a thicker needle) will have greater efficacy than a weaker stimulation (rotating needles with lower frequency and with a thinner needle). Acupuncture manipulation is not easy to describe very clearly, so most acupuncture RCTs are performed with electroacupuncture. We suggest that acupuncture RCTs may be successfully conducted by hand manipulation if the method is properly described, including details such as the reinforcing and reducing method and acupuncture dosage. In this way, acupuncture research will be more closely related to clinical practice.
Hence, the choice of control in an RCT depends on the type of research and the therapeutic effects of acupuncture being examined. The research design should take into consideration the placebo effect, a blinded design, subject selection, measurements chosen, and any contrast between the treatment and placebo groups. Such a design will correctly reflect the result without underestimating the effect of acupuncture.
J.-G. Lin and C.-H. Chen contributed equally to this work as cofirst authors.
The authors are grateful to Ms. Iona MacDonald and Ms. Ya-Ting Wu for their help in producing the final paper. This work was supported by Grants NSC-100-2320-B-039-029-MY2 and NSC-100-2320-B-039-018 from the National Science Council, Taipei, Taiwan, and in part by the Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH101-TD-B-111-004).