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Protocols For Clinical Trials (In Acupuncture)
If you are planning do some quotable research in Meridian Energy Therapies, here is a very useful set of guidelines to design and create a research project from the British Journal of Medical Acupuncture which can be easily adapted for use in our field.
June 1999 VOL 17(1) page 54
Protocols for Clinical Trials of Acupuncture
A written protocol is vital before conducting research, and should consist of sections on preliminary comments, subjects and methods, details of interventions and outcome measures, and methods of analysis. The process of developing the protocol provides a disciplined consideration of all aspects of the study.
Key wordsAcupuncture, Clinical trials, Ethics, Protocols.
IntroductionThe process of developing a protocol is a vital preparation for any research project, as it gives the researcher the opportunity to focus the mind systematically on every aspect of the study. Decisions must be made on exactly what has to be done to avoid bias, confounders and error. Possible difficulties must be anticipated and procedures devised in advance for dealing with them. The protocol should be written down in final form before the study starts. The aim is to produce a comprehensive protocol to cover all circumstances so that the investigator will not need to modify the plans later, nor make any decisions that have not been anticipated, in order to avoid the risk of introducing bias and compromising the value of the research.
The process of protocol development is also an important preparation for both ethics committee approval and grant application. Although both Local Research Ethics Committees (LRECs) and grant-awarding bodies will have their own detailed forms to complete, they will also want to see the formal protocol, and all the questions they may raise should have been considered already. Both these bodies will be interested basically in whether the researcher has defined a specific and important research question and has a good chance of answering it.
Some general guidelines for developing protocols follow, with the emphasis on controlled trials. No single set of guidelines can cover all circumstances but the general principles should be applicable. The very highest standards for designing, implementing and reporting research into drugs are contained in a European Union document entitled Good Clinical Practice (1) which aims to reassure the public that the data generated are credible and that the rights, integrity and confidentiality of subjects are protected. Good clinical practice involves detailed monitoring for quality assurance at every stage of the research, although in practice most clinical projects do not have the funds to pay for monitoring to this level. However, simply knowing about the highest available standards is likely to improve any researcher’s skill at developing a protocol.
A useful way of testing the robustness of every decision on the methodology of the proposed study is the Devil’s Advocate approach: this involves reversing all the hopes and predictions for the study. Thus, for example, it may be hoped that acupuncture will be more effective than the control intervention; but what if it is less effective, or their effectiveness turns out to be the same? Can useful conclusions still be drawn from all your hard work and effort?
Sections of the protocolTitle
The title should express the question(s) that the study is designed to answer, and briefly outline the essential method. For example, if the trial is to be randomised, then this word might appear somewhere in the title or sub-title. The title chosen now may be used for the final report.
Introduction or background
The Introduction should be as succinct as possible. Its usual structure consists, first, of introducing the medical condition, commenting on its frequency and its clinical or economic importance, and describing the current management, perhaps pointing out where conventional treatment is inadequate. Second, it should explain the possible role of acupuncture in treating the condition, or perhaps similar conditions; in designing a controlled trial, there needs to be a reasonable expectation that acupuncture will help patients, but not enough evidence to conclude that acupuncture is definitely effective for the condition. This is usually expressed as there being sufficient equipoise in clinical opinion.
Indication that a complete literature search has been done is necessary in the introduction, and essential references should be quoted to support each step of the argument. In Denmark, there is an even more demanding condition for ethical approval: the investigator should have first carried out a full systematic review on the topic! (2).
Finally, the text of the Introduction should be appropriate to act as the introduction to the final report or paper. There is a tendency for authors to use the introduction to display their extensive knowledge about the subject, but this is largely counterproductive. Readers need to learn the essential arguments, logically and clearly set out, without extraneous and baseless supposition.
Aim or research question
The researcher should be clear whether the objective of the study is to test the efficacy or the effectiveness of acupuncture. Efficacy is the extent to which acupuncture produces a beneficial result under ideal conditions, whereas effectiveness is a measure of the success of acupuncture when carried out in an average clinical environment. Efficacy studies have much tighter inclusion criteria, whereas effectiveness studies have more clinically relevant outcome measures.
Secondary questions may be asked in the trial, but should remain subordinate to the main question. However, they must be defined with just as much rigour and precision.
Subjects and methodsRecruitment
One common method of recruiting participants is from successive patients presenting with the particular condition in a clinic. Precise details should be given on how the participants are to be approached, and if it is by letter, the ethics committee will want to see it. Recruitment from media or other publicity may result in more chronic and resistant cases, or more complex psychological problems, than average. Include essential details for the screening process that will be applied, e.g. adults aged 18-65 years of either sex who have had the condition for at least 6 months.
alpha, the threshold for significance (which is typically set to 0.05)
Altman gives an excellent description of a simple method (3).
Inclusion and exclusion criteria
Exclusion criteria may include certain medical conditions (diagnosis of cancer or use of particular drugs, for example), contraindications to acupuncture (such as refusal to be needled, or major bleeding disorder), previous acupuncture treatment (for a trial that involves participant-blinding), and anything that will interfere with measuring the effect of the therapy, including lack of necessary skills (such as the ability to understand instructions on how to complete a questionnaire), the likelihood of getting better without the treatment (such as those with very mild stroke), and the use of other simultaneous treatments.
Intervention and control proceduresAcupuncture treatment
Define precisely what points will be used, how they will be stimulated and for how long with what sort of needles. If the treatment is to be individualised, state the criteria for choosing the points. This information needs to be comprehensive so that it can be repeated by other researchers and clinicians, otherwise there is little purpose in doing the research.
Schedule of interventions
Blinding of participants and evaluators
Patient evaluationFirst, specify what outcome measures will be used, and then consider the methods and schedule for collecting the data.
There are other measures, known as secondary outcome measures, which support or amplify the information from the primary measure or answer secondary questions. For example, if the primary outcome measure in a study of stroke is the Activities of Daily Living, secondary measures could include measures of spasticity, timed lo-metre walk, dysphagia, and Hospital Anxiety and Depression scale. Purpose-designed measures may also be used here, and may throw useful light on other aspect of the treatment effects that the researcher is interested in.
Statistical methodsMissing data
The method of dealing with missing data from participants who have dropped out should be specified before the study begins, to avoid the accusation of biasing the result. There are different ways of doing this: one conservative method involves substituting baseline data, which means assuming there has been no change. A more liberal method allows the substitution of an average of all the other participants’ results.
MiscellaneousCosts of study
Under this section, one should consider refunding travel costs and other out-of-pocket expenses for participants, in addition to costs of therapists, evaluators and (possibly) statistical advice and analysis, together with any equipment that may be required. Grant-awarding bodies will look for accurate estimates of all costs and clear justification for them. Ethics committees will look for any hint that the study may be biased to satisfy a sponsor, and ensure that the sponsor will not have the right to decline publication of the report.
Time schedule and feasibility
ConclusionA protocol is an essential starting point for all ethical research. Research in acupuncture has generally been of low standards, which means it has been open to bias, error and confounders. It is imperative to conduct good quality research in order to treat patients with the greatest possible benefit and least possible harm.
Adrian White MA BM BCh
of the British Medical Acupuncture Society