The placebo response and effect of time in a trial of acupuncture to treat nausea and vomiting in early pregnancy☆
Section snippets
INTRODUCTION
Nausea and vomiting in early pregnancy is a self-limiting condition, with women reporting a reduction in their symptoms as their pregnancy progresses towards the end of the first trimester. Clinical trials of interventions to reduce nausea and vomiting in pregnancy which omit a control group in the study design, have reported impressive results. In a recent randomised controlled trial of acupuncture to treat nausea and vomiting in early pregnancy, two control groups were included in the trial
METHODS
Women were volunteers to a randomised controlled trial evaluating the role of acupuncture to treat nausea and vomiting in early pregnancy, conducted at the Women’s and Children’s Hospital, South Australia. Women with a confirmed pregnancy, presenting at less than 14 weeks pregnant, with symptoms of nausea or vomiting were eligible to join the trial. Women were not eligible if there were any signs of clinical dehydration, or reason to suspect their symptoms were not due to their pregnancy. The
STATISTICAL ANALYSIS
It was an entry requirement that women experienced nausea at trial entry. A trial of 114 women would have an 80% power to detect a treatment effect of a 35% reduction in the number of women reporting nausea from 99 to 64% (alpha=0.05). The prevalence of vomiting is reported at 50% and to detect a 35% reduction in vomiting from 50 to 32.5% (alpha=0.05, beta=0.2), a sample size of 592 women was required. The sample size allowed for a 10% loss to follow up (pregnancy loss or withdrawal from the
RESULTS
Five hundred and ninety-three women were randomised to the trial between January 1997 and July 1999. Figure 1 summarises recruitment and return of data forms. We received nausea and vomiting data from 534 (90%) of women at the end of the first week of the trial and data from 443 (75%) at the end of the fourth week of the trial (Fig. 1). Assessments of the credibility of acupuncture was received from 419 (94%) women at baseline and from 391 (88%) women at the end of the study.
The median
WOMEN’S BELIEFS ABOUT ACUPUNCTURE
Women expressed positive views on the logic of acupuncture and confidence in the treatment improving their symptoms (Table 2). Women’s views did not differ between the acupuncture and sham groups at trial entry.
At the end of the trial, there was a difference in women’s views on recommending acupuncture (P<0.01) and their views on the success of acupuncture to treat other conditions between study groups (P<0.01; Table 2). Women’s confidence in recommending acupuncture to their friends was higher
PREVIOUS USE OF ACUPUNCTURE
It was feasible that women with previous acupuncture experience may have different beliefs or knowledge about acupuncture compared with the novice. Sixty-eight (17%) women reported previous acupuncture use. These women recorded higher scores on the logic of the treatment, compared with women who had no previous use of acupuncture (P<0.05; Table 3). Confidence in the treatment did not differ between women with previous acupuncture experience and women with no prior acupuncture experience.
GUESSING STUDY GROUP ALLOCATION
Three hundred and eighty (85%) women guessed which study group they were allocated to, but eight women were unable to guess. The majority of women (272, 71%) thought they were in an active acupuncture group (traditional acupuncture or PC6 acupuncture) and 100 women (26%) thought they were in the sham acupuncture group (Table 4).
We found women’s views on their perceived study group allocation differed according to their actual group allocation (P<0.0001). A higher proportion of women (102, 84%)
ESTIMATION OF THE PLACEBO RESPONSE AND THE EFFECT OF TIME ON NAUSEA
Estimates were made of the placebo response and improvement of nausea over time. Women’s nausea scores by study group (active acupuncture or sham acupuncture) are presented in Table 6.
Our data demonstrated an effect of time contributing to a decline in nausea at the end of the first and third weeks of the study (P<0.001; Table 6). There was no significant placebo response at the end of the first week but a significant placebo response was present at day 21 (P<0.001), and there was evidence that
DISCUSSION
We propose that an important aspect of the placebo response that we were able to explore in this trial was the strength of women’s expectations to improve. Women’s views on joining the study were positive and we suggest the method of recruiting women to the trial may have contributed to these optimistic views. The media was used to great effect to aid recruitment. However, the media sensationalised news of the trial, and women picking up the weekend newspaper were greeted by the heading
Acknowledgements
The authors wish to thank Kristyn Willson for her statistical support to this study.
Caroline Smith PhD, MSc, BSc, Lic Ac, Post-doctoral Research Officer, Department of Obstetrics and Gynaecology, The University of Adelaide, Women’s and Children’s Hospital, 72 King William Road, North Adelaide, SA 5006, Australia. Tel.: +61 88161 7565; Fax: +61 88161 7652; E-mail: [email protected]
References (9)
- et al.
Credibility of analogue therapy rationales
J. Behav. Ther. Exp. Psychiatry
(1972) - et al.
Introducing a placebo needle into acupuncture research
Lancet
(1998) - et al.
Acupuncture to treat nausea and vomiting in early pregnancy: randomised controlled trial
Birth
(2002) Credibility assessment in trials of acupuncture
Comp. Med. Res.
(1990)
Cited by (22)
The hip
2010, Acupuncture in Manual TherapyMeta-analysis of Acustimulation Effects on Nausea and Vomiting in Pregnant Women
2006, Explore: The Journal of Science and HealingCitation Excerpt :These trials were then evaluated using the Quality of Reports of Meta-analysis of Randomized Controlled Trials (QUOROM) guidelines.23,24 Three papers were excluded because repeated data were used from previous studies,25-27 and six additional papers were excluded because they were case studies.28-33 The remaining 17 papers were then evaluated for the quality of randomization and the quality of treatment.
Complementary and alternative medicine in obstetrics
2005, International Journal of Gynecology and ObstetricsThe terms 'acupuncture' and 'placebo' should be adequately defined in clinical trials (multiple letters) [1]
2003, Complementary Therapies in MedicinePatients' Expectancies to Acupuncture: A Systematic Review
2022, Journal of Integrative and Complementary MedicineIntegrative and complementary practices to control nausea and vomiting in pregnant women: a systematic review
2022, Revista da Escola de Enfermagem
Caroline Smith PhD, MSc, BSc, Lic Ac, Post-doctoral Research Officer, Department of Obstetrics and Gynaecology, The University of Adelaide, Women’s and Children’s Hospital, 72 King William Road, North Adelaide, SA 5006, Australia. Tel.: +61 88161 7565; Fax: +61 88161 7652; E-mail: [email protected]
Caroline Crowther MD, FRCOG, FRANZCOG, CMFM, Associate Professor, Department of Obstetrics and Gynaecology, The University of Adelaide, Women’s and Children’s Hospital, 72 King William Road, North Adelaide, SA 5006, Australia
- ☆
Funding The study was financially supported by the Department of Obstetrics and Gynaecology, the University of Adelaide and the Women’s and Children’s Hospital Research Foundation, Adelaide. Needles were donated by Cathy Herbal Products, Sydney, Australia.