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The effects of homeopathic Argentum nitricum on test anxiety
The effects of homeopathic Argentum nitricum on test anxiety D. G. Baker, 1,2 S. P. Myers, 2 I. Howden, 1 L. Brooks 2 1
School of Natural and Complementary Medicine, Southern Cross University, Lismore, Australia, 2 Australian Centre for Complementary Medicine Education and Research, Universities of Queensland and Southern Cross, Lismore, Australia
SUMMARY. Objectives: (1) To replicate a study of the efficacy of Argentum nitricum 12X in the reduction of test anxiety as demonstrated previously. (2) To investigate the correlation between individuals identified to match the A. nitricum profile and the reduction of test anxiety. To compare traditionally prepared homeopathic A. nitricum 12X with radionically-prepared A. nitricum 12X and placebo. Design: A double blind, placebo-controlled, randomised clinical trial with three arms. Setting: The study was conducted at Southern Cross University, Lismore, Australia. Subjects: Sixty-two test anxious university students. Interventions: Subjects were randomised to one of three groups: traditionally prepared homeopathic A. nitricum 12X, radionically-prepared A. nitricum 12X, or placebo. After screening, each group received treatment twice a day for 4 days after which they were re-tested. Outcome measures: Primary: The Revised Test Anxiety Scale. Secondary: The Test Anxiety Scale; 36-item A. nitricum questionnaire. Results: The results of this study did not replicate the Stanton study. No correlation between the reduction of test anxiety and the A. nitricum profile was demonstrated. No significant differences between treatments were demonstrated. Conclusion: This study demonstrated that homeopathic A. nitricum 12X does not reduce test anxiety in a general population of university students. © 2003 Elsevier Science Ltd. All rights reserved.
preparations was developed. In stark contrast to traditionally manufactured homeopathic preparations, radionic preparations are produced with no physical relationship between the original substance and the preparation. In 1982, H.E. Stanton2 reported a placebocontrolled trial on the effect of Argentum nitricum 12X on test anxiety in 40 subjects. Stanton demonstrated that the homeopathic preparation significantly improved test anxiety compared to a placebo, using the Test Anxiety Scale3 (TAS, P < 0.0042). The current study was designed with two principal aims. The first was to attempt to replicate the Stanton study and the second was to develop a methodological platform as a basis for future research into homeopathy. This research platform was dependent on the trial replication. Provided that the Stanton study was replicable, the intention was to
INTRODUCTION Background
D.G. Baker BNat (Hons), P.O. Box 1264, Byron Bay, NSW 2481, Australia. Tel.: +61 2 6685 6819; Fax: +61 2 6685 6974; E-mail: dbaker10@ scu.edu.au
Homeopathy is a system of medicine developed by Dr. Samuel Hahnemann just over 200 years ago and is based on the principle of Similia Similibus Curentur, “Like Cures Like”. Homeopathic preparations are manufactured from material that is serially diluted often to a point beyond which it is considered there is no trace of the original substance. Radionics is a system of diagnosis and treatment developed by Dr. Albert Abrams1 during the latter part of the nineteenth century. It is based on the purported transference of patient information via an electromagnetic medium, initially wires, then the telephone and then the earth itself. Utilising radionic theory, a process for the manufacture of homeopathic
Complementary Therapies in Medicine (2003), 11, 65–71 doi:10.1016/S0965-2299(03)00059-1
© 2003 Elsevier Science Ltd. All rights reserved.
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replicate this study numerous times using it to answer fundamental questions about homeopathy. The additional question built into this current study was a comparison between traditionally manufactured homeopathic preparations and radionic preparations. The specific hypotheses to be tested were that traditionally-prepared A. nitricum 12X will show: 1. significant improvement on the Revised Test Anxiety Scale (RTA)4 in comparison to placebo; 2. no difference on the RTA in comparison to placebo; 3. significant improvement on the RTA in comparison to radionically-prepared A. nitricum 12X; 4. significant correlation between the A. nitricum profile and the amount of positive change in the RTA.
METHODS A randomised, double blind, placebo-controlled clinical study with three parallel arms was undertaken. The first arm consisted of the traditionally-prepared A. nitricum, the second arm used the radionicallyprepared A. nitricum, and the third arm received a placebo. A power calculation, using variability data from Stanton, setting α and β at 0.05 and 0.8, respectively and looking for an effect size of 15%, from baseline to completion, required 20 subjects in each arm of
Fig. 1 Inclusion and exclusion criteria.
the study. Subjects were recruited from the student body of Southern Cross University, 70 of whom met eligibility requirements and were accepted into the study on a first come basis. Figure 1 lists the full inclusion/exclusion criteria. The study required each individual to take five drops of the allocated preparation in 30 ml of water twice daily for 4 consecutive days. Subjects were instructed to hold the liquid in the mouth for 30 s prior to swallowing and ensure the preparation was taken at least 30 min away from any oral intake, including smoking and toothpaste. Pre-trial testing used RTA as the primary outcome measurement and TAS and the A. nitricum profile questionnaire as secondary outcome measures. The A. nitricum profile questionnaire was developed specifically to assess the level of equivalence of the subject with the A. nitricum profile. Eight key A. nitricum symptoms were embedded in the 36 items, each item being scored using a 5-point Likert scale. Only the eight selected items were scored giving a possible total score of 40. Post-trial testing was conducted within 1 week of completion and used the RTA and the TAS. Brauer Biotherapies Pty Ltd (Adelaide) manufactured the homeopathic preparation specifically for the study. The A. nitricum 12X is the same preparation as that available commercially in Australia. The placebo and the carrier liquid for the radionic preparation were also supplied by Brauer and were from the same alcohol/water mixture used
The effects of homeopathic Argentum nitricum on test anxiety
for the traditionally prepared preparation. An independent practitioner, under the supervision of the researcher, prepared the radionic preparations using a potency simulator (Rae Extended Range Potency Simulator-B, England). The placebo preparation was indistinguishable from the other preparations. A randomisation schedule (blocks of four subjects) was generated by a staff member independent of the study using a random number generator program (Microsoft Excel, Microsoft Corp., Redmond, Washington, USA). Bottles containing the study preparations were numbered according to the schedule and distributed to subjects in numerical order. Access to the randomisation schedule was not available to researchers until all data had been collected. Statistical analysis was conducted using the SPSS for Windows 10.0.5 (SPSS Inc, Chicago, IL, USA). Parallel sets of analyses were run for the TAS and RTA variables. The statistical model employed was analysis of covariance (ANCOVA) with the post-score as the dependent variable, the pre-score as the covariate and the treatments as the factor. Sums of squares were sequentially partitioned so that the post-scores were adjusted for pre-scores. Alpha was set at 0.05. The Human Ethics Committee of Southern Cross University, acting according to the Australian National Health and Medical Research guidelines, approved the study. Informed consent was obtained from all subjects who participated in this study.
RESULTS One hundred and thirteen individuals, from the Southern Cross University student population, volunteered for screening. Seventy of these met the study entry criteria, were randomised and commenced the study. Average age of the subjects was 30.3 years, ranging from 18.5 to 52.2 years. Sixty-two subjects completed the study (53 females and 9 males), three withdrew, and five were lost to follow-up. Of the three withdrawals, one subject failed to comply with the study protocol, one subject left the university and one subject withdrew after commencing medication for illness. Data relevant to those who withdrew was not included in the analysis. Prior to analysis of pre- and post-treatment scores, the sample was assessed for homogeneity as a re-
Table 1
67
sult of factors that became evident as the study progressed. These secondary factors were: • a gender imbalance with a predominance of females across the groups; • screening outside the university examination period (3 weeks prior to examination commencement as well as 2 weeks of examination) against screening inside the examination period; • a time lag of more than 3 days between screening and the trial commencement against no time lag; • a time lag of more than 1 week between trial completion and post-testing against no time lag. ANCOVA with α set at 0.05 demonstrated no significant differences between groups, that is, the population sample was unaffected by the secondary factors.
PRIMARY OUTCOME ENDPOINTS Revised Test Anxiety Scale Analysis of covariance demonstrated no statistical difference between treatments on the post-score RTA means after adjustment for pre-score RTA means (F = 1.054; d.f. = 2.29; P = 0.362). The pre-treatment grand mean was calculated to be 60.706. Table 1 contains the means, standard error and confidence limits for the RTA post-treatment scores. Post hoc power calculations were conducted (α = 0.05 and β = 0.8) and indicated that the study had the power (power = 0.80) to show a difference of 1.81 on the RTA scores. This confirms that the study was adequately powered to demonstrate a 5% difference between groups.
SECONDARY OUTCOME ENDPOINTS Test Anxiety Scale Analysis of covariance demonstrated no statistical difference between treatments on the post-score TAS means after adjustment for pre-score TAS means (F = 0.827; d.f. = 2.39; P = 0.445). The pre-treatment grand mean was calculated to
RTA results
Treatment
Traditional homeopathy Radionic Placebo
n
21 18 23
Mean
64.133 59.268 58.717
S.E.
2.955 3.030 2.404
95% confidence interval Lower
Upper
58.089 53.070 53.800
70.178 65.465 63.635
Means, standard error and 95% confidence intervals for RTA results after adjustment of dependent variable (post-treatment mean) for the covariant (pre-treatment mean).
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Complementary Therapies in Medicine Table 2
TAS results
Treatment
n
Traditional homeopathy Radionic Placebo
Mean
21 18 23
22.357 20.270 22.427
S.E.
1.316 1.507 1.196
95% confidence interval Lower
Upper
19.696 17.223 20.007
25.018 23.318 24.846
Means, standard error and 95% confidence intervals for TAS results after adjustment of dependent variable (post-treatment mean) for the covariant (pre-treatment mean).
Table 3 Descriptive data: sample sizes, means and standard deviations for pre-treatment RTA and TAS scores of profile groups Profile group
Instrument
Argentum nitricum Non-A. nitricum A. nitricum Non-A. nitricum
RTA RTA TAS TAS
Traditional (n) 61.00 60.55 25.10 22.00
± ± ± ±
10.89 (10) 9.78 (11) 5.32 (10) 4.56 (11)
be 21.685. Table 2 contains the means, standard error and confidence limits for the TAS post-treatment scores. Post hoc power calculations were conducted (α = 0.05 and β = 0.8) and indicated that the study had the power (power = 0.80) to show a difference of 0.95 on the TAS scores, equivalent to a 3% difference between groups.
Argentum nitricum profile Analysis was conducted using the ANCOVA model. No significant difference was found between A. ni-
Radionic (n) 64.25 62.90 25.38 25.40
± ± ± ±
10.53 (8) 6.19 (10) 4.81 (8) 3.20 (10)
Placebo (n) 67.36 66.75 25.91 25.17
± ± ± ±
9.98 (11) 10.44 (12) 8.38 (11) 5.67 (12)
tricum and non-A. nitricum profile groups. A feature of this analysis is the smaller numbers in each of the treatment sub-groups caused by the classification of the overall sample into the two profile groups. Pre-treatment sample sizes, means and standard deviations are presented in Table 3 and these can be compared with the corresponding data for post-treatment RTA and TAS scores in Tables 4 and 5, respectively. Post hoc power calculations (α = 0.05 and β = 0.8) showed that the sub-group samples were too small to demonstrate less than a 22% difference between groups.
Table 4 Descriptive data: RTA means, standard error and 95% confidence intervals for profile groups by treatment Profile group
A. nitricum Non-A. nitricum A. nitricum Non-A. nitricum A. nitricum Non-A. nitricum
Treatment
Traditional homeopathy Traditional homeopathy Radionic Radionic Placebo Placebo
n
10 11 8 10 11 12
Mean
55.90 58.09 58.63 53.60 62.00 59.92
S.E.
4.24 3.19 4.60 2.99 3.88 4.80
95% confidence interval Upper
Lower
46.30 50.99 47.75 46.84 53.37 49.35
65.60 65.19 69.50 60.36 70.63 70.49
The means, standard errors and 95% confidence intervals for post-treatment RTA scores by profile groups and treatment.
Table 5 Descriptive data: TAS means, standard error and 95% confidence intervals for profile groups by treatment Profile group
Treatment
n
Mean
S.E.
A. nitricum Non-A. nitricum A. nitricum Non-A. nitricum A. nitricum Non-A. nitricum
Traditional homeopathy Traditional homeopathy Radionic Radionic Placebo Placebo
10 11 8 10 11 12
21.80 22.73 23.00 21.50 25.18 22.92
2.11 1.66 1.16 2.07 2.40 2.65
95% confidence interval Upper
Lower
17.03 19.03 20.25 16.81 19.83 17.08
26.57 26.42 25.75 26.19 30.54 28.75
The means, standard errors and 95% confidence intervals for post-treatment TAS scores by profile groups and treatment.
The effects of homeopathic Argentum nitricum on test anxiety Table 6 groups
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Pre-treatment test means and standard deviations by treatment
Study instrument
Traditional homeopathy
Radionic
Placebo
60.76 ± 10.1 23.48 ± 5.1 13.10 ± 1.9b
63.5 ± 8.2 25.39 ± 3.9
67.04 ± 10.0 25.52 ± 6.9 13.10 ± 1.9
RTA TAS Stanton TASa
Means and standard deviations for pre-treatment scores. a The Stanton study did not include the radionic preparation as a variable. b The Stanton study used the older 1960 version of the TAS whereas the current study employed the 1980 version.
Table 7
Comparison of pre-treatment TAS scores Pre-treatment mean
Expressed as percentage
13.10a 24.79b
81.9 67.0
Stanton TAS TAS
Conversion of pre-treatment TAS means to percentages. a Maximum score = 16. b Maximum score = 37.
BASELINE ANXIETY LEVELS The means and standard deviations of the unadjusted pre-treatment scores on the TAS were used to allow comparison with the previous study.2 Differences are noted between the TAS scores of the two studies because the previous study employed the 16-item 1960 version of the TAS whereas the current study employed the later 37-item 1978 version. Table 6 presents these data. Conversion of the pre-treatment TAS means to percentages allowed a comparison to be made between the two sets of data. This comparison revealed a mean anxiety level of 81.9% for the Stanton study and 67.0% for the present study. Table 7 presents these data.
DISCUSSION This study was set up to replicate and extend the study by Stanton.1 One of the drivers to replicate this study was the lack of replication of clinical trials in homeopathy. While the range of clinical conditions for which homeopathy has demonstrated efficacy is broad,5–7 only two attempts at replication were found in the literature. Jacobs et al.8,9 replicated the results of a trial of individualised homeopathic treatment of acute diarrhoea in two discrete paediatric populations, Nicaragua and Nepal, although there was some difference in the method of prescription and trial duration. Both trials demonstrated a significant outcome in favour of homeopathic treatment over placebo. Independent replication of these results by a different research group would add further weight to the strength of both the specific outcome and the evidence for homeopathic preparations being different from placebo.
Independent replication did occur in trials demonstrating the efficacy of Oscillococcinum® , a patented, commercially available preparation for the treatment of influenza.10,11 Both of these trials showed a significant decrease in symptoms in the active treatment group after 48 h when compared with placebo. The use of this complex is controversial as it does not reflect traditional homeopathic philosophy whereby the individual is prescribed the single remedy most closely matching the total symptom picture. A meta-analysis of seven Oscillococcinum® trials concluded that the preparation probably reduced the duration of influenza and influenza-like symptoms, however, the evidence was not strong enough to support a general recommendation for its use as a routine treatment. Confirmatory trials of Oscillococcinum® as a treatment are needed.12 Until homeopathic research is demonstrated to be independently replicable it will fail to meet an important criterion of scientific credibility. To this end, this study used a ‘state of the art’ test anxiety measurement instrument, implemented protocols to allow the comparison between traditionally manufactured and radionically manufactured preparations and tested the correlation between treatment and subjects identified as matching the A. nitricum profile. Analysis of the data revealed no significant reduction in test anxiety, no significant difference between treatments and no significant correlation between the profile and treatments. The null hypothesis could not be rejected. For replication purposes, this study did not include a stressor, the absence of which may have exerted some influence on outcomes. The study examined the effect of the treatments on trait test anxiety, that is, the subject’s predisposition to test
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anxiety. State anxiety, the more transitory reaction to a stressful event that includes the dimensions of worry and emotionality was untested. It may be the case that without the challenge of a stressor a change brought about by treatment is not apparent. If the empirically observed effect of A. nitricum on exam anxiety were diminution of the emotional component, its effect would not be observed. The measurement of the emotionality component of test anxiety may require the addition of another measurement instrument such as the State-Trait Anxiety Inventory.13 A comparison of pre-treatment means (Table 6) suggest a difference in the baseline anxiety levels between the Stanton study and this one. Conversion of the pre-treatment TAS means to percentages allowed a closer comparison to be made between the two sets of data (Table 7). This comparison revealed that the pre-treatment means of the Stanton sample were noticeably higher than the pre-treatment means for this study, the inference being that baseline anxiety levels for the two groups were quite different. It is possible that these differences contributed conflicting results. Differences in the method of recruitment could account for this. Where Stanton pre-selected the 40 subjects with the highest pre-treatment scores, this study set a threshold of 18/37 on the TAS14 as an entry criterion, with 60 subjects being defined as the minimum population according to power calculations. A methodological quality score of 36.4% was calculated for the Stanton study using an instrument designed by Chalmers et al.15 This demonstrated that the methodology used in the Stanton trial was flawed in several aspects. The trial report did not fully specify the blinding or randomisation design. Blinding, randomisation and compliance were untested. Inclusion and exclusion criteria were not described and no justification for the sample size was given. The statistical analysis was poorly reported with no description of a proper retrospective analysis and no statement of the method of treatment of withdrawal data. Homeopathically, the administration of homeopathic A. nitricum as a single specific preparation for test anxiety is in contrast to the homeopathic philosophy of individualisation of the prescription to suit each subject. The Stanton method arose from a reference to the use of A. nitricum as an anxiolytic, or, “funk pills”.16 In replicating the prior Stanton study, homeopathic preparation individualisation was not a factor in the current study and so an in-depth homeopathic interview to ascertain a remedy match was not considered a requirement. As a substitute for this process, the A. nitricum profile was developed as a strategy to identify those subjects who matched the remedy profile, that is, those subjects who would have been prescribed A. nitricum had an interview been conducted. Twenty-nine subjects (47%) matched the A. nitricum profile. Given the cohort recruited and the characteristic picture of A.
nitricum, such a high percentage may have been expected. The use of the questionnaire effectively changed the study from a three-armed study into one with six treatment sub-groups, each with a smaller sample size. Smaller sample size is usually associated with decreased study power. Post hoc power calculations (α = 0.05 and β = 0.8) showed that the reduced numbers in each sub-group were not adequate to demonstrate the expected 15% difference between the groups. In fact, the sub-group numbers only enabled an effect size of 22% or greater to be observed. This may be considered a significant design flaw. The study needed to recruit larger numbers or have been conducted exclusively with a population who matched the A. nitricum profile. It is recommended that further studies include a primary outcome measure for the state component of test anxiety, such as the State-Trait Anxiety Inventory.13 The inclusion of a stressor is necessary to stimulate the state test anxiety. In this case, university examinations are an ideal opportunity for such research. Consideration might be given to the inclusion of a positive anxiolytic against which the placebo and homeopathic preparations may be compared. As in homeopathic studies, problems of individualisation are inherent in clinical studies of traditional Chinese medicine. Bensoussan et al.17 overcame this by randomising subjects to receive an individualised Chinese formulation, placebo or a standardised Chinese formulation. This design can be readily adapted for further research into test anxiety where A. nitricum is used as the standardised preparation.
CONCLUSION The statistically significant results of the Stanton study were not replicated in the current study. A non-significant effect was demonstrated for the use of A. nitricum 12X in the reduction of test anxiety in a general student population. More specifically, this study has demonstrated no general effect of A. nitricum 12X on the reduction of the trait component of test anxiety in a university student population. Post hoc power calculations indicate that the sample size was adequate to detect a 5% difference between the groups had one existed. The emotional aspect of anxiety was not measured. The non-significant results of this study indicate that homeopathic A. nitricum 12X is not an appropriate preparation to use in the reduction of trait test anxiety in a general population of university students. There appears to be no difference between traditionally manufactured and radionically manufactured preparations and placebo. However, the questions raised by this study indicate that the use of homeopathic preparations in the reduction of test anxiety requires further research.
The effects of homeopathic Argentum nitricum on test anxiety ACKNOWLEDGEMENT The authors gratefully acknowledge the contribution of Brauer Biotherapies Pty Ltd (Adelaide) in the manufacture of the test preparations.
REFERENCES 1. Tansley DV. Radionics interface with the Ether-Fields. Devon, UK: Health Science Press, 1975. p. ix. 2. Stanton HE. Test and anxiety. A five-drop solution. Educ News 1981; 17: 12–15. 3. Sarason I. Experimental approaches to test anxiety attention and the uses of information. In: Spielberger CD, ed. Anxiety: Current trends in theory and research, vol 2. New York: Academic Press, 1972. p. 112. 4. Benson J, El-Zahhar N. Further refinement and validation of the Revised Test Anxiety Scale. Struct Equation Model 1994; I(3): 203–221. 5. Kleijnan J, Knipschild P, ter Riet G. Clinical trials of homeopathy. Br Med J 1991; 302: 316–323. 6. Linde K, Clausius N, Ramirez G et al. Are the clinical effects of homeopathy placebo effects? A meta analysis of placebo controlled trials. Lancet 1997; 350: 834–843. 7. Linde K, Melchart D. Randomised controlled trials of individualised homeopathy: a state-of-the-art review. J Altern Complement Med 1998; 4(4): 371–388. 8. Jacobs J, Jiminez LM, Gloyd S, Carares FE, Gaitan MP, Crothers D. Homeopathic treatment of diarrhoea. A randomised clinical trial in Nicaragua. Br Homeopathic J 1993; 82: 83–86.
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9. Jacobs J, Jiminez LM, Malthouse S, Chapman E, Crothers D, Masuk M, Jonas WB. Homeopathic treatment of acute childhood diarrhoea: results from a clinical trial in Nepal. J Altern Complement Med 2000; 6(2): 131–139. 10. Ferley JP, Zmirou D, D’Adhemar D, Balducci F. A controlled evaluation of a homeopathic preparation in the treatment of influenza-like symptoms. Br J Clin Pharmacol 1989; 27: 329–335. 11. Papp R, Schuback G, Beck E, Burkard G, Bengel J, Lehrl S, Belon P. Oscillococcinum® in patients with influenza-like syndromes: a placebo-controlled double-blind evaluation. Br Homeopathic J 1998; 87: 69–76. 12. Vickers AJ, Smith C. Homeopathic Oscillococcinum® for preventing and treating influenza and influenza-like syndromes (Cochrane Review). In: The Cochrane Library, Issue 4. Oxford: Update Software, 2002. 13. Spielberger CD. State-Trait Anxiety Inventory (STAI) form Y. Palo Alto, CA: Consulting Psychologists Press, 1983. 14. Sarason I. The Test Anxiety Scale (revised). In: Spielberger CD, Sarason IG, eds. Stress and anxiety, vol. 5. New York: Hemisphere/Wiley, 1978, p. 198. 15. Chalmers TC, Smith Jr H, Blackburn B et al. Method for assessing the quality of a randomised control trial. Control Clin Trials 1981; 2: 31–49. 16. Blackie MG. In: Stanton HE, ed. The patient, not the cure. Op. cit., p. 14. 17. Bensoussan A, Talley NJ, Hing M, Menzies R, Guo A, Ngu M. Treatment of Irritable Bowel Syndrome with Chinese herbal medicine: a randomised controlled trial. J Am Med Assoc 1998; 280(18): 155–159.
School of Natural and Complementary Medicine, Southern Cross University, Lismore, Australia, 2 Australian Centre for Complementary Medicine Education and Research, Universities of Queensland and Southern Cross, Lismore, Australia
SUMMARY. Objectives: (1) To replicate a study of the efficacy of Argentum nitricum 12X in the reduction of test anxiety as demonstrated previously. (2) To investigate the correlation between individuals identified to match the A. nitricum profile and the reduction of test anxiety. To compare traditionally prepared homeopathic A. nitricum 12X with radionically-prepared A. nitricum 12X and placebo. Design: A double blind, placebo-controlled, randomised clinical trial with three arms. Setting: The study was conducted at Southern Cross University, Lismore, Australia. Subjects: Sixty-two test anxious university students. Interventions: Subjects were randomised to one of three groups: traditionally prepared homeopathic A. nitricum 12X, radionically-prepared A. nitricum 12X, or placebo. After screening, each group received treatment twice a day for 4 days after which they were re-tested. Outcome measures: Primary: The Revised Test Anxiety Scale. Secondary: The Test Anxiety Scale; 36-item A. nitricum questionnaire. Results: The results of this study did not replicate the Stanton study. No correlation between the reduction of test anxiety and the A. nitricum profile was demonstrated. No significant differences between treatments were demonstrated. Conclusion: This study demonstrated that homeopathic A. nitricum 12X does not reduce test anxiety in a general population of university students. © 2003 Elsevier Science Ltd. All rights reserved.
preparations was developed. In stark contrast to traditionally manufactured homeopathic preparations, radionic preparations are produced with no physical relationship between the original substance and the preparation. In 1982, H.E. Stanton2 reported a placebocontrolled trial on the effect of Argentum nitricum 12X on test anxiety in 40 subjects. Stanton demonstrated that the homeopathic preparation significantly improved test anxiety compared to a placebo, using the Test Anxiety Scale3 (TAS, P < 0.0042). The current study was designed with two principal aims. The first was to attempt to replicate the Stanton study and the second was to develop a methodological platform as a basis for future research into homeopathy. This research platform was dependent on the trial replication. Provided that the Stanton study was replicable, the intention was to
INTRODUCTION Background
D.G. Baker BNat (Hons), P.O. Box 1264, Byron Bay, NSW 2481, Australia. Tel.: +61 2 6685 6819; Fax: +61 2 6685 6974; E-mail: dbaker10@ scu.edu.au
Homeopathy is a system of medicine developed by Dr. Samuel Hahnemann just over 200 years ago and is based on the principle of Similia Similibus Curentur, “Like Cures Like”. Homeopathic preparations are manufactured from material that is serially diluted often to a point beyond which it is considered there is no trace of the original substance. Radionics is a system of diagnosis and treatment developed by Dr. Albert Abrams1 during the latter part of the nineteenth century. It is based on the purported transference of patient information via an electromagnetic medium, initially wires, then the telephone and then the earth itself. Utilising radionic theory, a process for the manufacture of homeopathic
Complementary Therapies in Medicine (2003), 11, 65–71 doi:10.1016/S0965-2299(03)00059-1
© 2003 Elsevier Science Ltd. All rights reserved.
65
66
Complementary Therapies in Medicine
replicate this study numerous times using it to answer fundamental questions about homeopathy. The additional question built into this current study was a comparison between traditionally manufactured homeopathic preparations and radionic preparations. The specific hypotheses to be tested were that traditionally-prepared A. nitricum 12X will show: 1. significant improvement on the Revised Test Anxiety Scale (RTA)4 in comparison to placebo; 2. no difference on the RTA in comparison to placebo; 3. significant improvement on the RTA in comparison to radionically-prepared A. nitricum 12X; 4. significant correlation between the A. nitricum profile and the amount of positive change in the RTA.
METHODS A randomised, double blind, placebo-controlled clinical study with three parallel arms was undertaken. The first arm consisted of the traditionally-prepared A. nitricum, the second arm used the radionicallyprepared A. nitricum, and the third arm received a placebo. A power calculation, using variability data from Stanton, setting α and β at 0.05 and 0.8, respectively and looking for an effect size of 15%, from baseline to completion, required 20 subjects in each arm of
Fig. 1 Inclusion and exclusion criteria.
the study. Subjects were recruited from the student body of Southern Cross University, 70 of whom met eligibility requirements and were accepted into the study on a first come basis. Figure 1 lists the full inclusion/exclusion criteria. The study required each individual to take five drops of the allocated preparation in 30 ml of water twice daily for 4 consecutive days. Subjects were instructed to hold the liquid in the mouth for 30 s prior to swallowing and ensure the preparation was taken at least 30 min away from any oral intake, including smoking and toothpaste. Pre-trial testing used RTA as the primary outcome measurement and TAS and the A. nitricum profile questionnaire as secondary outcome measures. The A. nitricum profile questionnaire was developed specifically to assess the level of equivalence of the subject with the A. nitricum profile. Eight key A. nitricum symptoms were embedded in the 36 items, each item being scored using a 5-point Likert scale. Only the eight selected items were scored giving a possible total score of 40. Post-trial testing was conducted within 1 week of completion and used the RTA and the TAS. Brauer Biotherapies Pty Ltd (Adelaide) manufactured the homeopathic preparation specifically for the study. The A. nitricum 12X is the same preparation as that available commercially in Australia. The placebo and the carrier liquid for the radionic preparation were also supplied by Brauer and were from the same alcohol/water mixture used
The effects of homeopathic Argentum nitricum on test anxiety
for the traditionally prepared preparation. An independent practitioner, under the supervision of the researcher, prepared the radionic preparations using a potency simulator (Rae Extended Range Potency Simulator-B, England). The placebo preparation was indistinguishable from the other preparations. A randomisation schedule (blocks of four subjects) was generated by a staff member independent of the study using a random number generator program (Microsoft Excel, Microsoft Corp., Redmond, Washington, USA). Bottles containing the study preparations were numbered according to the schedule and distributed to subjects in numerical order. Access to the randomisation schedule was not available to researchers until all data had been collected. Statistical analysis was conducted using the SPSS for Windows 10.0.5 (SPSS Inc, Chicago, IL, USA). Parallel sets of analyses were run for the TAS and RTA variables. The statistical model employed was analysis of covariance (ANCOVA) with the post-score as the dependent variable, the pre-score as the covariate and the treatments as the factor. Sums of squares were sequentially partitioned so that the post-scores were adjusted for pre-scores. Alpha was set at 0.05. The Human Ethics Committee of Southern Cross University, acting according to the Australian National Health and Medical Research guidelines, approved the study. Informed consent was obtained from all subjects who participated in this study.
RESULTS One hundred and thirteen individuals, from the Southern Cross University student population, volunteered for screening. Seventy of these met the study entry criteria, were randomised and commenced the study. Average age of the subjects was 30.3 years, ranging from 18.5 to 52.2 years. Sixty-two subjects completed the study (53 females and 9 males), three withdrew, and five were lost to follow-up. Of the three withdrawals, one subject failed to comply with the study protocol, one subject left the university and one subject withdrew after commencing medication for illness. Data relevant to those who withdrew was not included in the analysis. Prior to analysis of pre- and post-treatment scores, the sample was assessed for homogeneity as a re-
Table 1
67
sult of factors that became evident as the study progressed. These secondary factors were: • a gender imbalance with a predominance of females across the groups; • screening outside the university examination period (3 weeks prior to examination commencement as well as 2 weeks of examination) against screening inside the examination period; • a time lag of more than 3 days between screening and the trial commencement against no time lag; • a time lag of more than 1 week between trial completion and post-testing against no time lag. ANCOVA with α set at 0.05 demonstrated no significant differences between groups, that is, the population sample was unaffected by the secondary factors.
PRIMARY OUTCOME ENDPOINTS Revised Test Anxiety Scale Analysis of covariance demonstrated no statistical difference between treatments on the post-score RTA means after adjustment for pre-score RTA means (F = 1.054; d.f. = 2.29; P = 0.362). The pre-treatment grand mean was calculated to be 60.706. Table 1 contains the means, standard error and confidence limits for the RTA post-treatment scores. Post hoc power calculations were conducted (α = 0.05 and β = 0.8) and indicated that the study had the power (power = 0.80) to show a difference of 1.81 on the RTA scores. This confirms that the study was adequately powered to demonstrate a 5% difference between groups.
SECONDARY OUTCOME ENDPOINTS Test Anxiety Scale Analysis of covariance demonstrated no statistical difference between treatments on the post-score TAS means after adjustment for pre-score TAS means (F = 0.827; d.f. = 2.39; P = 0.445). The pre-treatment grand mean was calculated to
RTA results
Treatment
Traditional homeopathy Radionic Placebo
n
21 18 23
Mean
64.133 59.268 58.717
S.E.
2.955 3.030 2.404
95% confidence interval Lower
Upper
58.089 53.070 53.800
70.178 65.465 63.635
Means, standard error and 95% confidence intervals for RTA results after adjustment of dependent variable (post-treatment mean) for the covariant (pre-treatment mean).
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Complementary Therapies in Medicine Table 2
TAS results
Treatment
n
Traditional homeopathy Radionic Placebo
Mean
21 18 23
22.357 20.270 22.427
S.E.
1.316 1.507 1.196
95% confidence interval Lower
Upper
19.696 17.223 20.007
25.018 23.318 24.846
Means, standard error and 95% confidence intervals for TAS results after adjustment of dependent variable (post-treatment mean) for the covariant (pre-treatment mean).
Table 3 Descriptive data: sample sizes, means and standard deviations for pre-treatment RTA and TAS scores of profile groups Profile group
Instrument
Argentum nitricum Non-A. nitricum A. nitricum Non-A. nitricum
RTA RTA TAS TAS
Traditional (n) 61.00 60.55 25.10 22.00
± ± ± ±
10.89 (10) 9.78 (11) 5.32 (10) 4.56 (11)
be 21.685. Table 2 contains the means, standard error and confidence limits for the TAS post-treatment scores. Post hoc power calculations were conducted (α = 0.05 and β = 0.8) and indicated that the study had the power (power = 0.80) to show a difference of 0.95 on the TAS scores, equivalent to a 3% difference between groups.
Argentum nitricum profile Analysis was conducted using the ANCOVA model. No significant difference was found between A. ni-
Radionic (n) 64.25 62.90 25.38 25.40
± ± ± ±
10.53 (8) 6.19 (10) 4.81 (8) 3.20 (10)
Placebo (n) 67.36 66.75 25.91 25.17
± ± ± ±
9.98 (11) 10.44 (12) 8.38 (11) 5.67 (12)
tricum and non-A. nitricum profile groups. A feature of this analysis is the smaller numbers in each of the treatment sub-groups caused by the classification of the overall sample into the two profile groups. Pre-treatment sample sizes, means and standard deviations are presented in Table 3 and these can be compared with the corresponding data for post-treatment RTA and TAS scores in Tables 4 and 5, respectively. Post hoc power calculations (α = 0.05 and β = 0.8) showed that the sub-group samples were too small to demonstrate less than a 22% difference between groups.
Table 4 Descriptive data: RTA means, standard error and 95% confidence intervals for profile groups by treatment Profile group
A. nitricum Non-A. nitricum A. nitricum Non-A. nitricum A. nitricum Non-A. nitricum
Treatment
Traditional homeopathy Traditional homeopathy Radionic Radionic Placebo Placebo
n
10 11 8 10 11 12
Mean
55.90 58.09 58.63 53.60 62.00 59.92
S.E.
4.24 3.19 4.60 2.99 3.88 4.80
95% confidence interval Upper
Lower
46.30 50.99 47.75 46.84 53.37 49.35
65.60 65.19 69.50 60.36 70.63 70.49
The means, standard errors and 95% confidence intervals for post-treatment RTA scores by profile groups and treatment.
Table 5 Descriptive data: TAS means, standard error and 95% confidence intervals for profile groups by treatment Profile group
Treatment
n
Mean
S.E.
A. nitricum Non-A. nitricum A. nitricum Non-A. nitricum A. nitricum Non-A. nitricum
Traditional homeopathy Traditional homeopathy Radionic Radionic Placebo Placebo
10 11 8 10 11 12
21.80 22.73 23.00 21.50 25.18 22.92
2.11 1.66 1.16 2.07 2.40 2.65
95% confidence interval Upper
Lower
17.03 19.03 20.25 16.81 19.83 17.08
26.57 26.42 25.75 26.19 30.54 28.75
The means, standard errors and 95% confidence intervals for post-treatment TAS scores by profile groups and treatment.
The effects of homeopathic Argentum nitricum on test anxiety Table 6 groups
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Pre-treatment test means and standard deviations by treatment
Study instrument
Traditional homeopathy
Radionic
Placebo
60.76 ± 10.1 23.48 ± 5.1 13.10 ± 1.9b
63.5 ± 8.2 25.39 ± 3.9
67.04 ± 10.0 25.52 ± 6.9 13.10 ± 1.9
RTA TAS Stanton TASa
Means and standard deviations for pre-treatment scores. a The Stanton study did not include the radionic preparation as a variable. b The Stanton study used the older 1960 version of the TAS whereas the current study employed the 1980 version.
Table 7
Comparison of pre-treatment TAS scores Pre-treatment mean
Expressed as percentage
13.10a 24.79b
81.9 67.0
Stanton TAS TAS
Conversion of pre-treatment TAS means to percentages. a Maximum score = 16. b Maximum score = 37.
BASELINE ANXIETY LEVELS The means and standard deviations of the unadjusted pre-treatment scores on the TAS were used to allow comparison with the previous study.2 Differences are noted between the TAS scores of the two studies because the previous study employed the 16-item 1960 version of the TAS whereas the current study employed the later 37-item 1978 version. Table 6 presents these data. Conversion of the pre-treatment TAS means to percentages allowed a comparison to be made between the two sets of data. This comparison revealed a mean anxiety level of 81.9% for the Stanton study and 67.0% for the present study. Table 7 presents these data.
DISCUSSION This study was set up to replicate and extend the study by Stanton.1 One of the drivers to replicate this study was the lack of replication of clinical trials in homeopathy. While the range of clinical conditions for which homeopathy has demonstrated efficacy is broad,5–7 only two attempts at replication were found in the literature. Jacobs et al.8,9 replicated the results of a trial of individualised homeopathic treatment of acute diarrhoea in two discrete paediatric populations, Nicaragua and Nepal, although there was some difference in the method of prescription and trial duration. Both trials demonstrated a significant outcome in favour of homeopathic treatment over placebo. Independent replication of these results by a different research group would add further weight to the strength of both the specific outcome and the evidence for homeopathic preparations being different from placebo.
Independent replication did occur in trials demonstrating the efficacy of Oscillococcinum® , a patented, commercially available preparation for the treatment of influenza.10,11 Both of these trials showed a significant decrease in symptoms in the active treatment group after 48 h when compared with placebo. The use of this complex is controversial as it does not reflect traditional homeopathic philosophy whereby the individual is prescribed the single remedy most closely matching the total symptom picture. A meta-analysis of seven Oscillococcinum® trials concluded that the preparation probably reduced the duration of influenza and influenza-like symptoms, however, the evidence was not strong enough to support a general recommendation for its use as a routine treatment. Confirmatory trials of Oscillococcinum® as a treatment are needed.12 Until homeopathic research is demonstrated to be independently replicable it will fail to meet an important criterion of scientific credibility. To this end, this study used a ‘state of the art’ test anxiety measurement instrument, implemented protocols to allow the comparison between traditionally manufactured and radionically manufactured preparations and tested the correlation between treatment and subjects identified as matching the A. nitricum profile. Analysis of the data revealed no significant reduction in test anxiety, no significant difference between treatments and no significant correlation between the profile and treatments. The null hypothesis could not be rejected. For replication purposes, this study did not include a stressor, the absence of which may have exerted some influence on outcomes. The study examined the effect of the treatments on trait test anxiety, that is, the subject’s predisposition to test
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Complementary Therapies in Medicine
anxiety. State anxiety, the more transitory reaction to a stressful event that includes the dimensions of worry and emotionality was untested. It may be the case that without the challenge of a stressor a change brought about by treatment is not apparent. If the empirically observed effect of A. nitricum on exam anxiety were diminution of the emotional component, its effect would not be observed. The measurement of the emotionality component of test anxiety may require the addition of another measurement instrument such as the State-Trait Anxiety Inventory.13 A comparison of pre-treatment means (Table 6) suggest a difference in the baseline anxiety levels between the Stanton study and this one. Conversion of the pre-treatment TAS means to percentages allowed a closer comparison to be made between the two sets of data (Table 7). This comparison revealed that the pre-treatment means of the Stanton sample were noticeably higher than the pre-treatment means for this study, the inference being that baseline anxiety levels for the two groups were quite different. It is possible that these differences contributed conflicting results. Differences in the method of recruitment could account for this. Where Stanton pre-selected the 40 subjects with the highest pre-treatment scores, this study set a threshold of 18/37 on the TAS14 as an entry criterion, with 60 subjects being defined as the minimum population according to power calculations. A methodological quality score of 36.4% was calculated for the Stanton study using an instrument designed by Chalmers et al.15 This demonstrated that the methodology used in the Stanton trial was flawed in several aspects. The trial report did not fully specify the blinding or randomisation design. Blinding, randomisation and compliance were untested. Inclusion and exclusion criteria were not described and no justification for the sample size was given. The statistical analysis was poorly reported with no description of a proper retrospective analysis and no statement of the method of treatment of withdrawal data. Homeopathically, the administration of homeopathic A. nitricum as a single specific preparation for test anxiety is in contrast to the homeopathic philosophy of individualisation of the prescription to suit each subject. The Stanton method arose from a reference to the use of A. nitricum as an anxiolytic, or, “funk pills”.16 In replicating the prior Stanton study, homeopathic preparation individualisation was not a factor in the current study and so an in-depth homeopathic interview to ascertain a remedy match was not considered a requirement. As a substitute for this process, the A. nitricum profile was developed as a strategy to identify those subjects who matched the remedy profile, that is, those subjects who would have been prescribed A. nitricum had an interview been conducted. Twenty-nine subjects (47%) matched the A. nitricum profile. Given the cohort recruited and the characteristic picture of A.
nitricum, such a high percentage may have been expected. The use of the questionnaire effectively changed the study from a three-armed study into one with six treatment sub-groups, each with a smaller sample size. Smaller sample size is usually associated with decreased study power. Post hoc power calculations (α = 0.05 and β = 0.8) showed that the reduced numbers in each sub-group were not adequate to demonstrate the expected 15% difference between the groups. In fact, the sub-group numbers only enabled an effect size of 22% or greater to be observed. This may be considered a significant design flaw. The study needed to recruit larger numbers or have been conducted exclusively with a population who matched the A. nitricum profile. It is recommended that further studies include a primary outcome measure for the state component of test anxiety, such as the State-Trait Anxiety Inventory.13 The inclusion of a stressor is necessary to stimulate the state test anxiety. In this case, university examinations are an ideal opportunity for such research. Consideration might be given to the inclusion of a positive anxiolytic against which the placebo and homeopathic preparations may be compared. As in homeopathic studies, problems of individualisation are inherent in clinical studies of traditional Chinese medicine. Bensoussan et al.17 overcame this by randomising subjects to receive an individualised Chinese formulation, placebo or a standardised Chinese formulation. This design can be readily adapted for further research into test anxiety where A. nitricum is used as the standardised preparation.
CONCLUSION The statistically significant results of the Stanton study were not replicated in the current study. A non-significant effect was demonstrated for the use of A. nitricum 12X in the reduction of test anxiety in a general student population. More specifically, this study has demonstrated no general effect of A. nitricum 12X on the reduction of the trait component of test anxiety in a university student population. Post hoc power calculations indicate that the sample size was adequate to detect a 5% difference between the groups had one existed. The emotional aspect of anxiety was not measured. The non-significant results of this study indicate that homeopathic A. nitricum 12X is not an appropriate preparation to use in the reduction of trait test anxiety in a general population of university students. There appears to be no difference between traditionally manufactured and radionically manufactured preparations and placebo. However, the questions raised by this study indicate that the use of homeopathic preparations in the reduction of test anxiety requires further research.
The effects of homeopathic Argentum nitricum on test anxiety ACKNOWLEDGEMENT The authors gratefully acknowledge the contribution of Brauer Biotherapies Pty Ltd (Adelaide) in the manufacture of the test preparations.
REFERENCES 1. Tansley DV. Radionics interface with the Ether-Fields. Devon, UK: Health Science Press, 1975. p. ix. 2. Stanton HE. Test and anxiety. A five-drop solution. Educ News 1981; 17: 12–15. 3. Sarason I. Experimental approaches to test anxiety attention and the uses of information. In: Spielberger CD, ed. Anxiety: Current trends in theory and research, vol 2. New York: Academic Press, 1972. p. 112. 4. Benson J, El-Zahhar N. Further refinement and validation of the Revised Test Anxiety Scale. Struct Equation Model 1994; I(3): 203–221. 5. Kleijnan J, Knipschild P, ter Riet G. Clinical trials of homeopathy. Br Med J 1991; 302: 316–323. 6. Linde K, Clausius N, Ramirez G et al. Are the clinical effects of homeopathy placebo effects? A meta analysis of placebo controlled trials. Lancet 1997; 350: 834–843. 7. Linde K, Melchart D. Randomised controlled trials of individualised homeopathy: a state-of-the-art review. J Altern Complement Med 1998; 4(4): 371–388. 8. Jacobs J, Jiminez LM, Gloyd S, Carares FE, Gaitan MP, Crothers D. Homeopathic treatment of diarrhoea. A randomised clinical trial in Nicaragua. Br Homeopathic J 1993; 82: 83–86.
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9. Jacobs J, Jiminez LM, Malthouse S, Chapman E, Crothers D, Masuk M, Jonas WB. Homeopathic treatment of acute childhood diarrhoea: results from a clinical trial in Nepal. J Altern Complement Med 2000; 6(2): 131–139. 10. Ferley JP, Zmirou D, D’Adhemar D, Balducci F. A controlled evaluation of a homeopathic preparation in the treatment of influenza-like symptoms. Br J Clin Pharmacol 1989; 27: 329–335. 11. Papp R, Schuback G, Beck E, Burkard G, Bengel J, Lehrl S, Belon P. Oscillococcinum® in patients with influenza-like syndromes: a placebo-controlled double-blind evaluation. Br Homeopathic J 1998; 87: 69–76. 12. Vickers AJ, Smith C. Homeopathic Oscillococcinum® for preventing and treating influenza and influenza-like syndromes (Cochrane Review). In: The Cochrane Library, Issue 4. Oxford: Update Software, 2002. 13. Spielberger CD. State-Trait Anxiety Inventory (STAI) form Y. Palo Alto, CA: Consulting Psychologists Press, 1983. 14. Sarason I. The Test Anxiety Scale (revised). In: Spielberger CD, Sarason IG, eds. Stress and anxiety, vol. 5. New York: Hemisphere/Wiley, 1978, p. 198. 15. Chalmers TC, Smith Jr H, Blackburn B et al. Method for assessing the quality of a randomised control trial. Control Clin Trials 1981; 2: 31–49. 16. Blackie MG. In: Stanton HE, ed. The patient, not the cure. Op. cit., p. 14. 17. Bensoussan A, Talley NJ, Hing M, Menzies R, Guo A, Ngu M. Treatment of Irritable Bowel Syndrome with Chinese herbal medicine: a randomised controlled trial. J Am Med Assoc 1998; 280(18): 155–159.