Volume 174 Issue 2

Research The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of Australian women A randomised controlled trial Susan R Davis, Esther M Briganti, Run Q Chen Fabien S Dalais, Michael Bailey and Henry G Burger MJA 2001; 174: 68-71 For editorial comment, see Eden Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Obstetrics & gynaecology and women's health Abstract Objective: To evaluate the effects of a defined formula of Chinese medicinal herbs (CMH) on menopausal symptoms. Design: A double-blind randomised placebo-controlled trial. Methods: Between August 1998 and April 1999, 55 postmenopausal Australian women recruited from an urban population completed 12 weeks of intervention with either a defined formula of CMH (n = 28) or placebo (n = 27) taken twice daily as a beverage. Main outcome measures: The primary end-point was change in frequency of vasomotor events (hot flushes and night sweats). The secondary end-points were changes in score for the domains measured in the Menopause Specific Quality of Life (MENQOL) Questionnaire. Results: There was a reduction in average weekly frequency of vasomotor events with CMH (- 15%; 95% CI, - 31% to + 1%) and with placebo (- 31%; 95% CI, - 42% to - 21%). The difference between groups favoured the use of placebo; however, this was not significant (P = 0.09). Although significant reductions in scores for the various domains of the MENQOL Questionnaire were observed for both CMH and placebo, there were no significant differences between the two treatment groups for any domain. There was evidence for effect modification by previous use of natural therapies for the vasomotor, physical and sexual domains of the MENQOL Questionnaire: women with no prior use of natural therapies for their menopausal symptoms responded to therapy, whereas prior users did not. Conclusions: The defined formula of CMH was no more effective than placebo in reducing vasomotor episodes in Australian postmenopausal women, or in improving any of the four symptom domains in the MENQOL Questionnaire. Three of the MENQOL Questionnaire domains were modified by prior use of natural therapies. This finding has implications for future studies. In Australia, more than a third of postmenopausal women are troubled by vasomotor symptoms.1 Although hormone replacement therapy (HRT) eliminates 60% of flushes within three months,2 a significant number of postmenopausal women have absolute or relative contraindications to HRT, or are unwilling to use this therapy.3Chinese herbal medicine has been used for centuries in China for treating menopausal symptoms, and is still in current use. Clinical trials in China have shown significant effects of Chinese herbal medicine in alleviating menopausal symptoms in Chinese women,4,5 but these effects may not be generalisable. We therefore conducted a double-blind, randomised, placebo-controlled study of the effects of a modified traditional formula of Chinese medicinal herbs (CMH) on vasomotor symptoms in Australian postmenopausal women. Methods Study population Approval for the study was obtained from the Human Research and Ethics Committee of Monash Medical Centre. All patients gave written informed consent. The study was conducted between August 1998 and April 1999. Inclusion criteria: Patients were recruited through the Jean Hailes Foundation Newsletter, newspapers, radio station interviews and the Medical Unit of the Jean Hailes Foundation. Non-Asian women aged 45 to 70 years, who had lived in Australia for at least 10 years, were postmenopausal (> 12 months' amenorrhoea and follicle-stimulating hormone level > 25 IU/L), and reported at least 14 hot flushes or night sweats per week were eligible for the study. Exclusion criteria: Women were excluded if they had used HRT, CMH or other natural therapies (evening primrose oil, yam cream, progesterone cream or any other over-the-counter preparation for menopausal symptoms) during the eight weeks before baseline, or if they had preexisting gastrointestinal, renal or liver disease, diabetes mellitus requiring treatment, uncontrolled hypertension, undiagnosed vaginal bleeding, systemic glucocorticosteroid use, or were undergoing cancer therapy. Women who had consumed a high phytoestrogen diet (according to a food frequency questionnaire6) for the four weeks before baseline were also excluded. Randomisation: Subjects were randomised to CMH or placebo using a randomisation chart constructed by randomising numbers 1 to 88 into two groups using Microsoft Excel.7 Study intervention The defined formula of CMH for the active preparation used in the trial is listed in Box 1. Placebo was cornstarch with a bitter taste enhancer. All herbs are listed with the Australian Therapeutic Goods Administration, and were administered within standard dosage levels. All were screened for heavy metal contamination by Ningbo Daekang Herbs Co Ltd (Ningbo, China) and the National Analytical Laboratories in Melbourne. The CMH and placebo were produced by Ningbo Daekang Herbs Co Ltd as granules soluble in warm water, and each dose was prepackaged in identical aluminium foil sachets. Patients were instructed to drink one sachet of granules dissolved in 200 mL of warm water, twice a day. Both solutions had similar unusual tastes. A four-week supply was dispensed at each treatment visit. The design did not accommodate the diagnostic and therapeutic principles of Chinese medicine, but was for analysing the therapeutic efficacy of the herbs. Outcome measures Demographics, body mass index (kg/m2), medical history, gynaecological history, and use of previous HRT or natural therapies for menopausal symptoms were documented at baseline. The primary end-point of the study was the effect of treatment on the frequency of vasomotor symptoms. Each woman completed a daily diary of the frequency of hot flushes and night sweats for four weeks before the commencement of treatment and for the entire 12 weeks of the study period. The secondary end-points of the study were the effect of treatment on each of the four domains of the Menopause Specific Quality of Life (MENQOL) Questionnaire and on urinary phytoestrogen excretion. The MENQOL Questionnaire is a validated instrument that tests physical, vasomotor, psychosexual and sexual domains of quality of life.8 It can differentiate between women according to quality of life, as well as measure changes in quality of life. A minimum score of zero corresponds to no symptoms and a maximum score of seven corresponds to extremely bothersome symptoms. The smallest clinically relevant change is a difference in one point within the domains, representing a 15% change. As dietary history is a poor guide to phytoestrogen ingestion, a potential confounding factor, we also measured urinary phytoestrogen excretion in women participating in the trial. Total urinary daidzein and genistein excretion was measured in 24-hour urine samples at baseline and at Week 12.9 Subjects were asked not to modify their dietary pattern for the study period. Sample size and statistical analysis The sample size was calculated based on the primary end-point of change in hot flushes and night sweats. A clinically relevant effect of treatment is considered to be at least a 40% reduction in vasomotor events.10-12 Anticipating a 30% placebo response, for power of 80% and a significance level of 5%, a sample size of 28 subjects in each treatment group was required. This sample size was also adequate to determine a clinically relevant change of score of one point in the MENQOL domains.8Statistical analysis was performed using Statview.13 For each participant the percentage change from baseline in the frequency of hot flushes and night sweats for each of the 12 weeks of the study period, and the absolute difference in scores between Week 12 and baseline for each domain of the MENQOL Questionnaire, were calculated. Repeated analysis of variance was used to analyse the effects of treatment within and between groups over the study period for these outcomes. The Wilcoxon two-sample test was used to analyse the effect of treatment on the excretion of the phytoestrogen metabolites daidzein and genistein. Additional analysis was undertaken to determine the effect of baseline characteristics (age, BMI, duration of amenorrhoea, and previous use of HRT or natural therapies for relief of vasomotor symptoms) on the average percentage change in vasomotor symptoms and on the difference in scores for each domain of the MENQOL Questionnaire. This was performed using analysis of covariance. Continuous variables were categorised into two groups based on the median value (age: < 55 years and ≥ 55 years; BMI: ≤ 25 kg/m2 and > 25 kg/m2; duration of amenorrhoea: < 4 years and ≥4 years). Results Study population Of the 78 subjects who were randomised, 28 in the active group and 27 in the placebo group completed the study (Box 2). Baseline characteristics of those who withdrew and those who completed the study were similar, except for the previous use of natural therapies for menopausal symptoms, which was more frequent in those who withdrew. Most withdrawals were owing to taste intolerance and occurred within the first week after randomisation. There were no significant differences in baseline characteristics between the placebo and CMH treatment groups (Box 3). Effect of intervention on vasomotor symptoms The frequency of vasomotor symptoms was reduced in both CMH and placebo groups (CMH: - 15.0%; 95% CI, - 31.1% to + 1.2%; placebo: - 31.4%; 95% CI, - 41.5% to - 21.2%). The difference between the two groups was not significant (+16.4%; 95% CI, + 35.2% to - 2.4%; P = 0.09). A progressive decline in the frequency of vasomotor symptoms with treatment duration was seen in both groups (CMH, P = 0.001; placebo, P = 0.006). The difference between the two groups was not significant (P = 0.26). Effect of intervention on MENQOL Questionnaire scores A reduction in score was seen in all four domains of the questionnaire with both CMH and placebo. This was significant only for the physical (- 1.14; 95% CI, - 1.78 to - 0.50), vasomotor (- 0.57; 95% CI, - 0.89 to - 0.24) and sexual (- 0.69; 95% CI, - 1.10 to - 0.28) domains in the CMH group, and the physical (- 0.74; 95% CI, - 1.41 to - 0.07) domain in the placebo group. However, the difference between the two treatment groups was not significant for any of the four domains. Effect of baseline characteristics on treatment effect The effects of baseline characteristics are shown in Box 4. Women with more than four years of amenorrhoea had a significantly greater response to placebo than to CMH (Box 4). A significantly greater reduction in score was seen with CMH compared with placebo in the vasomotor domain of the MENQOL Questionnaire for the baseline characteristics of age < 55 years, BMI ≤ 25 kg/m2, and previous non-users of natural therapies (Box 4). There was a significant difference in treatment effect between those who had and those who had not previously used natural therapies for the physical, vasomotor and sexual domain scores. A significant difference in treatment effect was also seen for the two age categories and for the two BMI categories for the vasomotor domain score. Phytoestrogen measurements No significant change was seen in daidzein or genistein excretion with either CMH or placebo, and there was no difference between the two treatment groups. Adverse events The frequency of reported adverse events did not differ between the two groups. Abdominal bloating was reported by three women treated with placebo and one with CMH; two women with CMH reported lower abdominal pain and loose stools. Fifteen women (placebo, 9; CMH, 6) reported headache, joint pain or dizziness. Discussion In our study of extracts of CMH administered as granules reconstituted to a beverage, there was no significant or clinically relevant difference in the frequency of vasomotor symptoms between placebo and CMH therapy. Furthermore, there was no significant or clinically relevant difference in the scores for the four domains of the MENQOL Questionnaire. This study was adequately powered to distinguish at least a 40% reduction in the frequency of vasomotor symptoms, as well as a clinically meaningful reduction in the MENQOL domain scores with treatment. The effect of CMH compared with placebo on the frequency of vasomotor symptoms was not modified by age, BMI, duration of amenorrhoea, previous use of HRT or natural therapies. However, the scores for the physical, vasomotor and sexual domains were modified by previous use of natural therapies: women who had no prior use of natural therapies for their menopausal symptoms responded to therapy, whereas prior users did not. The vasomotor domain was also modified by age and BMI. It is of interest that prior users of natural therapies showed a clinically relevant greater response to placebo than CMH for the physical, vasomotor and sexual domains. That baseline characteristics, particularly prior natural therapy use, significantly modified the response to treatment in this study is an important observation of relevance to future studies of natural therapies. That our findings differ from reports of studies conducted in China4,5 is most likely owing to differences in study design. The Chinese studies have not been placebo-controlled, have employed raw herbs, and have allowed for modification of herbal constituents during the studies according to individual responses.4,5 The preparation of medicinal tea from raw herbs is very time consuming, and was deemed a major obstacle to compliance in a non-Asian study population. The granules used in this study were supplied by a company that routinely prepares herbs in this manner for medicinal purposes in China, and there is no evidence to indicate that the granules do not retain the therapeutic properties of the original herbs. In summary, our study of the effects of CMH versus placebo on vasomotor events and menopausal symptoms in non-Asian Australian women found no overall benefit of the CMH. The modifying effects of prior use of natural therapies is an important positive finding that deserves further investigation and confirmation. Acknowledgements The study was supported by a research grant from the Australasian Menopause Society. Cathay Herbal, Sydney, kindly donated the study preparations. We thank Dr Tikky Wattanapenpaiboon of Monash University for assistance in the evaluation of the food frequency questionnaire, and Associate Professor Flavia Cicuttini of Monash University for valuable input to this study. Dr James C G Doery of Monash Medical Centre offered guidance in testing the study herbal preparations for heavy metal contamination. We also thank all the participants. References Dennerstein L, Smith AM, Morse C, et al. Menopausal symptoms in Australian women. Med J Aust 1993; 159: 232-236. Abraham S, Perz J, Clarkson R, Llewellyn-Jones D. Australian women's perception of hormone replacement therapy over 10 years. Maturitas 1995; 21: 91-95. Waldman TN. Menopause: when hormone replacement therapy is not an option. Part 1 [review]. Women's Health 1998; 7: 559-565. Yao SA. Review on the research and development of Chinese medicine in menopausal syndrome (in Chinese). J Tradit Chin Med 1994; 35: 112-114. Li CJ. Menopausal symptoms. In: Dai DY, editor. Current application and research of Chinese medicine and pharmacology: gynecology. Shanghai: Shanghai University of Traditional Chinese Medicine Publishing House, 1995; 174-182. Wahlqvist M, Kouris-Blazos A, Hsu-Hage B, et al. Food habits and health status of Anglo-Celtic Australians. A questionnaire on food frequency. Melbourne: Monash University. Microsoft Excel 95 [computer program]. Redmond: Microsoft Corporation, 1995. Hilditch JR, Lewis J, Peter A, et al. A menopause specific quality of life questionnaire: development and psychometric properties. Maturitas 1996: 24; 161-175. Dalais FS, Rice GE, Wahlqvist ML, et al. Effects of dietary phytoestrogens in postmenopausal women. Climacteric 1998; 1: 124-129. Murkies AL, Lombard C, Strauss BJ, et al. Dietary flour supplementation decreases postmenopausal hot flushes: effect of soy and wheat. Maturitas 1995; 21: 189-195. Poller L, Thomson JM, Coope J. A double-blind cross-over study of piperazine oestrone sulphate and placebo with coagulation studies. Br J Obstet Gynaecol 1980; 87: 718-725. Hailes JD, Nelson BJ, Schneider M, et al. Conjugated equine oestrogen versus placebo in the management of menopausal symptoms. Med J Aust 1981; 2: 341-342. Statview [computer program]. Abacus Concepts Inc, Berkeley, CA, 1995. (Received 28 Aug, accepted 1 Oct, 2000) Authors' details The Jean Hailes Foundation, Melbourne, VIC. Susan R Davis, FRACP, PhD, Associate Professor and Director of Research; Run Q Chen, MA, Master's Student; Henry G Burger, AO, FRACP, FAA, Consultant Endocrinologist. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC. Esther M Briganti, MB BS, FRACP, Senior Lecturer; Michael Bailey, MSc, Statistical Consultant. International Health and Development Unit, Monash University, Clayton, VIC. Fabien S Dalais, PhD, Senior Research Officer. Reprints will not be available from the authors. Correspondence: Associate Professor S R Davis, The Jean Hailes Foundation, 173 Carinish Road, Clayton, VIC 3168. suedavisATnetlink.com.au Make a comment 1: The defined formula of the Chinese medicinal herbs Pharmaceutical name Chinese name Dose* Rehmannia glutinosa Cornus officinalis Dioscorea opposita Alisma orientalis Paeonia suffruticosa Poria cocos Citrus reticulata Lycium chinensis Albizzia julibrissin Zizyphus jujuba Eclipta prostrata Ligustrum lucidum Shu Di Huang Shan Zhu Yu Shan Yao Ze Xie Dan Pi Fu Shen Chen Pi Di Gu Pi He Huan Pi Suan Zao Ren Han Lian Cao Nu Zhen Zi 15 10 12 8 8 12 5 20 15 10 15 10 *Dose in grams of dried herb per day. Back to text 2: Flow diagram of participation in the study CMH = Chinese medical herbs. HRT = hormone replacement therapy. Back to text 3: Baseline characteristics of study participants Baseline characteristics Placebo Chinese medicinal herbs P Number Age (years)* Body mass index (kg/m2)* Duration of amenorrhoea (years)* Previous use of hormone replacement therapy Previous use of natural therapies Frequency of hot flushes or night sweats, per week* MENQOL domains Physical domain* Vasomotor domain* Psychosexual domain* Sexual domain* 27 54.1 (52.6, 55.5) 26.1 (24.3, 27.9) 4.6 (3.0, 6.2) 44.4% 37.0% 46.6 (35.4, 57.8) 5.6 (4.9, 6.2) 4.0 (3.3, 4.8) 3.9 (3.3, 4.6) 3.4 (2.5, 4.3) 28 56.3 (54.3, 58.3) 25.7 (23.9, 27.5) 5.8 (3.9, 7.7) 53.6% 35.7% 46.2 (38.75, 53.7) 5.5 (5.2, 6.5) 3.8 (3.1, 4.5) 3.6 (3.0, 4.2) 3.3 (2.4, 4.3) 0.07 0.75 0.34 0.50 0.92 0.94 0.57 0.67 0.45 0.95 *Values are mean (95% confidence limits). Back to text 4: Effect of Chinese medicinal herbs (CMH) compared with placebo on frequency of vasomotor symptoms and MENQOL domain scores, by baseline characteristics* Mean reduction in MENQOL domain score (95% confidence limits) Mean reduction in vasomotor symptoms (95% confidence limits) Physical Vasomotor Psychosexual Sexual Age +8.1% (-16.5%, +32.8%) -0.74 (-1.91, +0.42) -0.94 (-1.74, -0.14) -0.22 (-1.00, +0.57) -0.72 (-2.82, +1.38) ≥55 years +17.9% (-10.7%, +46.5%) -0.36 (-1.76, +1.03) +0.51 (-0.56, +1.58) +0.10 (-0.77, +0.96) -0.14 (-1.30, +1.03) Body mass index ≤25 kg/m2 +7.1% (-21.4%, +35.5%) -1.16 (-2.57, +0.25) -0.85 (-1.61, -0.08) -0.17 (-1.01, +0.68) -1.00 (-2.66, +0.65) >25 kg/m2 +26.2% (-0.48%, +52.9%) +0.28 (-0.92, +1.48) +0.42 (-0.73, +1.58) +0.13 (-0.68, +0.95) +0.18 (-1.46, +1.82) Amenorrhoea < 4 years +4.8% (-24.6%, +34.2%) -0.28 (-1.72, +1.17) -0.31 (-1.67, +1.06) +0.18 (-0.81, +1.16) +0.52 (-1.59, +2.62) ≥4 years +26.8% (+3.8%, +49.9%) -0.49 (-1.70, +0.72) -0.09 (-0.61, +0.42) -0.08 (-0.70, +0.54) -0.96 (-2.08, +0.16) Previous use of hormone replacement therapy No +12.1% (-14.4%, +38.6%) -0.69 (-2.02, +0.65) -0.24 (-1.47, +1.00) +0.03 (-0.74, +0.80) +0.17 (-1.74, +1.40) Yes +22.4% (-6.3%, +51.2%) -0.05 (-1.37, +1.27) -0.16 (-0.75, +0.43) +0.02 (-0.90, +0.95) -0.59 (-2.43, +1.26) Previous use of natural therapies for symptoms of menopause No +11.1% (-11.2%, +33.3%) -1.16 (-2.35, +0.02) -1.09 (-1.68, -0.49) -0.33 (-1.07, +0.41) -1.19 (-2.75, +0.37) Yes +26.1% (-10.0%, +62.3%) +0.93 (-0.38, +2.24) +1.30 (-0.06, +2.67) +0.63 (-0.29, +1.56) +1.15 (-0.33, +2.64) *Values are the percentage or point difference between CMH and placebo (CMH effect minus placebo effect). As vasomotor symptoms and all domain scores improved for both treatment groups, a negative value indicates a greater effect from CMH and a positive value indicates a greater effect from placebo. For shaded values, 95% confidence limits do not include 0. For boxed values, there is a significant difference in treatment effect between the two categories (P Back to text

Susan R Davis · Esther M Briganti · Run Q Chen · Fabien S Dalais · Michael Bailey · Henry G Burger

Research Use of fake tanning lotions in the South Australian population Kerri R Beckmann, Barbara A Kirke, Kieran A McCaul and David M Roder MJA 2001; 174: 75-78 Abstract - Methods - Results - Discussion - Conclusions - References - Authors' Details - - More articles on Public and environmental health Abstract Objective: To explore the relationship between the use of fake tanning lotions and repeated sunburn among South Australian adults, with a view to informing the Anti-Cancer Foundation of South Australia's (ACFSA) policy on fake tanning products. Study design: Population survey. Participants: 2005 South Australians aged 18 years or older, selected randomly from the electronic White Pages. Main outcome measures: Self-reported use of fake tanning lotions in the past 12 months; frequency of sunburn over summer; and various sun-protective behaviours. Results: 2005 of the 2536 eligible participants (79%) were surveyed by telephone. Fake tan use was most prevalent among women (15.9%), people aged 18-24 years (15.4%), and people with household incomes above $40 000 per year (11.9%). Fake tan users were more likely than non-users to use sunscreens (81.3% v 56.5%; P < 0.001), but less likely to take other precautions such as wearing hats (40.9% v 51.0%; P = 0.04) and protective clothing (22.3% v 34.1%; P = 0.005). They were also more likely to report having been burnt more than once over summer (26.2% v 16.5%; P = 0.025). Multivariate analysis indicates a statistically significant association between fake tan use and repeated sunburn (odds ratio, 2.07; 95% confidence interval, 1.17-3.69), which was independent of age, sex, skin type and sun-protection practices. Conclusion: Users of fake tanning products may be at greater risk of repeated sunburn. The ACFSA sees no justification at this stage for altering its present policy position of not actively promoting the use of fake tanning lotions as a means of reducing sunburn. Anticancer organisations in Australia have been conducting programs aimed at reducing Australia's high rate of skin cancer for over two decades.1 The main objective of these programs is to encourage people to reduce their exposure to solar ultraviolet radiation, the major contributing factor to the development of skin cancer.2In Australia public awareness about the dangers of overexposure to the sun is generally high. In spite of this, a suntan is still desired by some sectors of the community -- in particular, young, fashion-conscious people.3,4 Skin cancer prevention programs have attempted to change attitudes that value tanned skin as attractive and healthy with such messages as "there is no such thing as a safe tan" and "a tan is a sign of skin damage". Last year, Chapman challenged anticancer organisations to consider the role that fake tanning lotions might play in reducing sun exposure, suggesting that they should be assessed as a potential harm-reduction strategy.5 The Anti-Cancer Foundation of South Australia (ACFSA) has, for a number of years, provided information on fake tanning lotions. While not actively encouraging their use, the information suggests that, for those desiring a tan, using fake tanning lotions is preferable to exposure to artificial or solar ultraviolet radiation. In October 1999, the ACFSA included a question on the use of fake tanning lotions in a Health Monitor Survey along with questions on skin type, experience of sunburn and frequency of wearing hats, cover-up clothing, applying sunscreen and seeking shade. This article reports the findings of that survey and discusses them in relation to the position taken by the ACFSA regarding fake tanning lotions. Methods Questions relating to sun exposure and ultraviolet radiation protective behaviours, including one relating to the use of fake tanning lotions, were asked of a random sample of South Australians, by computer-assisted telephone interviewing. These questions (Box 1) were part of a larger health-related survey organised and conducted by the Department of Human Services, South Australia, in October 1999. Except for the question relating to fake tan use, these questions have been used routinely in monitoring sun-protection behaviours in South Australia and were originally validated as written questions in a national Secondary School Children's Survey conducted triennially since 1990.6 The question on fake tan use is a slightly modified version of a question asked in Victorian surveys in 1993 and 1995.7,8Ethical approval for the survey that incorporated the questions used in this study was obtained through the Department of Human Services, with legal authorisation under section 64d of the South Australian Health Commission Act (1976). A sample of 3400 residences from rural and metropolitan areas within South Australia was drawn from the electronic White Pages. One adult from each household (the person whose birthday was the most recent) was invited to participate. Two thousand and five interviews were conducted from the 2536 households that could be contacted after six callback attempts, giving a participation rate of 79.1%. All data were weighted by age, sex and region, and on the probability of selection within the household. The population profile for weighting was obtained from the Australian Bureau of Statistics' estimated population for South Australia, 1997. Geographical region was defined as either metropolitan or country region. Both descriptive analysis of the survey data and logistic regression modelling were undertaken using STATA version 6,9 as this software allows calculation of robust estimates of standard error using methods devised by Huber10 and White.11 Consequently, variance estimates are adjusted for the data weighting. The relationship between fake tan use and reported sunburn over summer was examined using logistic regression modelling, allowing adjustment for age, sex, skin type and sun-protective behaviours. We first constructed a model containing known risk factors for sunburn and then added fake tan use to this model to establish if this improved the fit of the model. "Having been burnt two or more times during the previous summer" was the dependent (outcome) variable. For each of the sun protective behaviour questions, respondents were coded as regular users if they indicated that they "usually, almost always, or always" took such precautions when out in the sun for an hour or more, and were coded as irregular users if they indicated that they "never, rarely or sometimes" took these measures. Results Based on results from this survey, the estimated prevalence of fake tanning lotion use during the past 12 months among South Australians aged 18 years or more was 8.7% (95% confidence interval [CI], 7.3%-10.5%). The prevalence of fake tan use among various subgroups of the population is shown in Box 2. The use of fake tanning lotions is most common among younger people, particularly women, with the peak prevalence being 28% among young women aged 18-24 years. Fake tan use is also more common among those who report that their skin burns before tanning, compared with those whose skin just tans or just burns. Fake tan use also appears to be related to household income, with those with relatively high household incomes (above $40 000 per year) more likely to use fake tanning lotions. Individuals who had used fake tanning lotions in the past year were more likely to report regularly using sunscreen with a sun protection factor (SPF) of 15+ or higher when in the sun than non-users (81% v 57%; P < 0.001). However, they were less likely to report regularly wearing hats (41% v 51%; P = 0.04) or protective clothing (22% v 34%; P = 0.005). They reported seeking shade at levels similar to those who had not used fake tanning lotions (80% v 76%, P = 0.4). Those who had used fake tanning lotions were also more likely to report having been burnt two or more times during the previous summer (26% v 17%; P = 0.025) (Box 3). Factors such as age, skin type, sex and regular sun-protective behaviours are likely to confound the association between fake tan use and risk of burning. Results of logistic regression modelling, which takes into account the effects of these potential confounders, indicate an increased risk among fake tan users of having been sunburnt more than once (odds ratio [OR], 2.07; 95% CI, 1.17-3.69), as shown in Box 4. As the use of fake tanning lotions was much more prevalent among women than men, we also undertook regression analyses for women and men separately. No association between fake tan use and sunburn was found among men (OR, 0.90; 95% CI, 0.14-5.97). This was most probably owing to the fact that only 12 men reported using fake tanning lotions. There was, however, a strong association between using fake tanning lotions and repeated sunburn among women (OR, 2.47; 95% CI, 1.38-4.42). Discussion While the overall prevalence of fake tan use among adult South Australians is low (8.7%; 95% CI, 7.3%-10.5%), the use of fake tanning lotions is fairly common in younger women, with more than one in four women aged 18-24 years reporting having used fake tanning lotions in the past year. These findings are consistent with the reported prevalence of use in Victoria.7,8Respondents who reported using fake tanning lotions were more likely to report regularly using SPF 15+ or higher sunscreen when out in the sun during summer, but were less likely to report wearing hats or protective clothing. Fake tan users were more likely to report being sunburnt two or more times over the past summer. When other known risk factors were taken into account, fake tan users had twice the risk of repeated sunburn over summer compared with non-users. The only previously reported findings in relation to the association between fake tan use and sunburn are from two surveys conducted in Victoria, one in 19937 and one in 1995.8 The first of these surveys found a higher prevalence of sunburn among fake tan users (66% v 46%), while the latter survey found no difference (39% v 40%). The inconsistency of these two reports may have been owing to the relatively small sample size of each survey (n < 700). Owing to the limited nature of the questions in this survey, we were unable to determine whether fake tanning lotions were used just at the start of the season to give a tanned look before a sun-induced tan could be achieved, or throughout the summer as a substitute for sunbathing. Given the timing of the survey (ie, spring), there may be some inaccuracy in people's recall of sunburn in the previous summer. However, it seems unlikely to us that one group would have been more or less likely to under-report having been sunburnt, so any recall effect would have been equivalent in both groups. Another limitation in relation to the timing and cross-sectional nature of the survey is the inability to establish a temporal relationship. In some cases, sunburn may have preceded the use of fake tanning lotions. We can not conclude that fake tan use contributes directly to an increased risk of sunburn. We can only suggest that the behaviours of fake tan use and sun exposure may be linked. A further limitation of this study is that we did not ask about the reason for or frequency of use. We do not know whether there are differences in the risk of sunburn among those who use fake tanning lotions only on special occasions (eg, theatrical performances) compared with those who use such products regularly to maintain a tanned appearance. This lack of detail does not negate the finding that, as a whole, those who use fake tanning lotions are at greater risk of sunburn. Regardless of when and why people use fake tanning lotions, the results of this survey do not offer any evidence that use of fake tanning lotions, as currently practised, protects against sunburn. However, since this is an observational study, we can not rule out the possibility that the use of fake tanning lotions may actually offer some protection. It is conceivable that, had users not been applying fake tanning lotions, sunburn levels could have been even higher in this group. Further clarification of this issue would require a longitudinal (experimental) study design. Our results suggest that, rather than reducing their sun exposure, fake tan users are more likely to be exposing their skin to damaging levels of ultraviolet radiation than non-users. The evidence also suggests that, in general, fake tan users take fewer precautions to protect their skin from the sun. While fake tan users are more likely to report using sunscreens, they appear to rely on sunscreens alone for sun protection rather than using multiple strategies, as recommended by the Anti-Cancer Foundation. Some fake tan users may believe that the tanned effect provided by fake tanning lotions offers protection against the sun. Further confusion may arise in cases where their chosen brand of tanning lotion contains sunscreen. An inspection of fake tanning lotions currently available in South Australia showed that most brands do not include a sunscreen, and many state on the label that the fake tan does not provide protection against solar ultraviolet radiation. Some brands also include the advice to use a regular SPF 30+ sunscreen when going into the sun. However, a few brands of fake tanning lotions do contain sunscreen, varying in their sun protection factor from 4 to 15. One commonly available product with an SPF 4 rating states on its label, "UV Protection: Protects you in the sun, providing 4 times your natural sunburn protection". While technically correct, the protection would apply only to the period immediately after application and not for the time that the tan remains visible on the skin. Such claims are obviously very misleading. Anticancer organisations advise that sunscreens need to be reapplied regularly, ideally two-hourly, to maintain adequate protection. If such advice was followed when using a fake tanning lotion containing a sunscreen, the colour of the tan would deepen with each application. Also, it may take up to four hours for the tan colour to fully develop. Most products recommend removal of dry or flaky skin before applying the fake tanning lotion. The need to do this and the effect of repeated applications on tan colour are likely to preclude regular reapplication of fake tanning lotions, thereby increasing the likelihood of users risking sunburn if they rely on the protection offered by one application. In our view, including a sunscreen in a fake tanning lotion offers no obvious benefit. On the contrary, it has the potential to generate a false sense of protection which may lead to sunburn in fake tan users. Conclusions In response to the discussion posed by Chapman5 in relation to the use of fake tanning lotions as a "harm minimisation" approach, the ACFSA was prompted to review its policy in relation to the promotion and sale of fake tanning lotions. The results of this study do not point to a reduced risk of harmful sun exposure among fake tan users. Rather, they suggest an elevated risk of sunburn. In the light of these findings, the ACFSA sees no justification for altering its current position on the use of fake tanning lotions. The use of fake tanners is not actively promoted by the ACFSA. However, where there is a strong desire for a tan, people are advised that the use of fake tanning lotions is a better alternative than sunbathing or using a solarium. They are also advised that a fake tan does not provide protection against the sun and are warned about the limited protection offered by products that contain a sunscreen. More in-depth investigation of why and when fake tanning lotions are used, and the extent to which fake tan users believe they are protected from the harmful effects of the sun while using such products, is needed to inform education strategies and guide any policy change by organisations such as the ACFSA. The potential of the labelling of fake tan products containing sunscreens to be misleading needs to be brought to the attention of the relevant authorities. References Gray N. Report of the Chairman of the Education Committee. Australian Cancer Society Annual Report, 1979. Sydney: ACS, 1979: 9. Armstrong BK. Stratospheric ozone and health. Int J Epidemiol 1994; 23: 873-885. Arthey S, Clarke V. Suntanning and Sun protection: A review of the psychological literature. Soc Sci Med 1995; 40 (2): 265-274. Clarke V, Williams T, Arthey S. Skin type and optimistic bias in relation to the sun protection and suntanning behaviors of young adults. J Behav Med 1997; 20: 207-222. Chapman S. Faking it: should cancer control agencies promote fake tanning lotions? Med J Aust 1999; 170: 603-604. Broadstock M, Borland R, Hill D. Knowledge, attitudes and reported behaviours relevant to sun protection and suntanning in adolescents. Psychol Health 1996; 11: 527-539. Purchase M, Borland R. Public reaction to the 1992/93 SunSmart campaign: results from a representative survey of Victorians. SunSmart Evaluation Studies 3. Melbourne: Anti-Cancer Council of Victoria, 1994: 93. Dixon H, Cappiello M, Borland R. Reaction to the 1994/95 SunSmart campaign: results from a representative household survey of Victorians. SunSmart Evaluation Studies 5. Melbourne: Anti-Cancer Council of Victoria, 1997: 64. Stata version 6 [computer program]. College Station, TX: Stata Corporation, 1999. Huber PJ. The behavior of maximum likelihood estimates under non-standard conditions. Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability 1967; 1: 221-233. White H. A heteroskedasticity-consistent covariance matrix estimator and direct test for heteroskedasticity. Econometrica 1980; 48: 817-830. (Received 21 Mar, accepted 31 Jul, 2000) Authors' Details Anti-Cancer Foundation of South Australia, Adelaide, SA. Kerri R Beckmann, BSc(Hons), MPH, Program Evaluation Officer; Barbara A Kirke, DipN, MPHC, Skin Cancer Prevention Project Officer. Collaborative Research Centre for Asthma, University Department of Medicine, Sir Charles Gairdner Hospital, Perth, WA. Kieran A McCaul, BSc, MPH, Biostatistician. Epidemiology Branch, South Australian Department of Human Services, Adelaide, SA. David M Roder, AM, MPH, DDSc, Director. Reprints will not be available from the authors. Correspondence: Ms K R Beckmann, Anti-Cancer Foundation of South Australia, PO Box 929, Unley, SA 5061. kbeckmannATcancersa.org.au Make a comment Back to text Back to text Back to text 4: Factors associated with being burnt more than once over summer All respondents Women only Adjusted Adjusted odds ratio 95% CI P odds ratio 95% CI P Fake tan use Non-users Users 1.00 2.07 - 1.17-3.69 0.013 2.47 1.38-4.42 0.002 Sex Female Male 1.00 2.99 - 2.09-4.29 - - - Age (group years) 65+ 18-24 25-34 35-44 45-54 55-64 1.00 13.70 5.83 4.72 2.46 1.27 - 7.00-26.78 3.19-10.65 2.66-8.38 1.34-4.53 0.61-2.66 0.004 0.529 15.46 4.40 5.12 3.56 0.40 5.34-44.77 1.71-11.34 2.04-12.86 1.37-9.23 0.09-1.65 0.002 0.001 0.009 0.203 Skin type Just tan Burn then tan Just burn 1.00 2.07 2.47 - 1.20-3.56 1.47-4.16 0.009 0.001 1.86 2.12 0.69-5.01 0.83-5.39 0.222 0.117 Sunscreen use Irregular Regular 1.00 1.03 - 0.72-1.48 0.876 0.82 0.44-1.49 0.509 Hat wearing Irregular Regular 1.00 0.69 0.48-0.98 0.038 0.91 0.52-1.59 0.746 Protective clothing Irregular Regular 1.00 0.63 - | 0.44-0.91 0.014 0.95 0.56-1.61 0.856 Shade seeking Irregular Regular 1.00 0.91 - 0.62-1.32 0.604 0.55 0.30-1.01 0.056 *Logistic regression modelling using forced entry of all variables. Separate models for all respondents and women only. Back to text

Kerri R Beckmann · Barbara A Kirke · Kieran A McCaul · David M Roder

The Research Enterprise Australian medical patents granted in the United States in 1984-1999 Eugen Mattes and Michael C Stacey MJA 2001; 174: 83-87 Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Law Abstract Objective: To describe all medical patents granted in the United States to Australian-resident inventors between 1984 and 1999. Data sources: All patent data originated from the US Patent and Trademark Office. Data for 1984-1994 were compiled by CHI Research Inc, and data for 1995-1999 were obtained from the Community of Science website. Main outcome measures: Number of medical patents granted in the US to Australian-resident inventors; assignees (owners) of these medical patents; proportion of these medical patents related to biotechnology. Results: From 1984 to 1999, 7835 utility patents were granted in the US to Australian-resident inventors. Of these, 1308 patents (17%) were identified as medical patents; 489 (37%) of these were biotechnology patents. Medical patents account for an increasing proportion of all US patents granted to Australian inventors, increasing from 10% in 1984 to 25% in 1999. Biotechnology accounted for an increasing proportion of medical patents, rising from 10% to 55% between 1984 and 1999. More than half the medical patents are owned by commercial interests, and 33% by only 14 organisations, six of which are universities and their affiliated institutions. Conclusion: Only a few organisations account for most of the patenting of medical technology. The inventors and their organisations listed on medical patents could be canvassed when developing government policy and targeted for support in commercialising their medical technology. Interest in harnessing the economic value of medical technology conceived and created in Australia has been growing.1-3 This is reflected in the creation of Cooperative Research Centres (CRCs). Since 1991, 67 CRCs have been created, of which 10 have a medical focus.4 Despite these initiatives, medical inventors, unlike sports stars, are virtually unrecognised by the Australian public and scientific community. Where do our new technologies in medicine come from -- industry, universities, or the lone inventor? We chose to study all patents for inventions (utility patents) granted in the United States to Australian residents. These patents are economically more significant than patents granted in Australia, as the increased cost and effort of patenting in another country is thought to filter out trivial inventions.5 Because of the importance of the US market, the US is also the first country where multinational corporations submit their patent applications outside the patent's country of origin.6 Thus, Australian patents in the US are arguably the most important subset of Australian patents in other countries.7 Our aim was to describe Australian medical patents and to compare them with non-medical patents. Methods This is a descriptive study of patents granted in the US from 1984 to 1999 to inventors resident in Australia. Utility patents were examined, with design and plant patents excluded. Sources of data All patent data originated from the US Patent and Trademark Office. US patents listing one or more Australian-resident inventors for 1984-1994 were compiled by Computer Horizons Incorporated (CHI) Research Inc8 of the US and, for 1995-1999, were updated from the Community of Science website.9 Our electronic patent database contained the following information for each patent: year of patent being granted; US patent registration number; title of patent; all listed inventors and assignees and their country of residence; and number of citations of scientific literature. When required for classifying patents, the patent abstracts or full patents were examined on the Internet (using the US patent registration number) at either the US Patent and Trademark Office Web Patent Database Centre,10 or the Delphion (formerly IBM) Intellectual Property Network.11 Categorisation of medical patents As there are no published guidelines for selecting medical patents, we defined a medical patent as any technology used for: managing patients and their illnesses, such as drugs, diagnostic tests, surgical instruments, and rehabilitation devices (dental technologies were excluded); preventing illness, such as sunscreen lotion; or medical research, such as laboratory instruments. Generic technologies used in other fields, such as information technology, were excluded. Patents were classified as medical, possibly medical or non-medical after reading the title and the name of the assignees (owners). For all patents labelled as possibly medical, we read the abstract, and if necessary the complete patent, to properly classify the patent. Medical patents related to biotechnology12 were identified separately, and included devices, processes, DNA sequences, transgenic animals and manufacturing processes in the medical industry. Biotechnology patents related to other industries, such as agriculture, mining and food processing, were excluded. Describing inventors and assignees The inventors and assignees on patents were sorted alphabetically in Microsoft Excel,13 and any errors or differences in spelling were corrected. The median number of inventors and assignees per patent was calculated as a measure of collaboration. The assignees on each patent were categorised as a business, university, government, research institute, CRC, non-government organisation, technology transfer office, or individual. Categorising was usually straightforward using the name of the assignee, but, if there was uncertainty, a search was made on the Internet using the search engine Dogpile.14 Data analysis The data were stored, tabulated and graphed in Microsoft Excel,13 and statistical analysis was conducted using SPSS for Windows.15 The χ2 test or Fisher's exact test was used to compare independent proportions. The Mann-Whitney U test was used to compare medians. Ethical issues All the information in this study, including the names of inventors and companies, is publicly available on numerous patent bibliographic databases. Results From 1984 to 1999, 7835 utility patents were granted in the US to Australian-resident inventors. From examination of the title and assignee names of these patents, 9% (673/7835) were classified as medical and 35% (2767/7835) as possibly medical. The abstracts of all patents classified as possibly medical were examined, and 11% (869/7835) required the full patent to be read. In total, 1308 (17%) Australian patents in the US were classified as medical. Of these, 489 (37%) were biotechnology patents. Trends in medical patenting The annual number of patents granted in the US to Australian-resident inventors in 1984-1999 more than doubled, rising from 310 to 800 (Box 1). During this 16-year period, the proportion of medical patents rose from 10% (30/310) to 25% (202/800). Biotechnology accounted for an increasing proportion of medical patents, rising from 10% (3/30) to 55% (112/202) over the same period. Comparison of medical and non-medical patents In terms of inventors, medical patents were: more likely to have multiple inventors listed, with a median of two inventors per medical patent versus one per non-medical patent (P < 0.001, Box 2); and twice as likely to be part of an international collaboration, with co-inventors who are residents of other countries in 21% (275/1308) of medical and 10% (649/6527) of non-medical patents (P < 0.001, Box 3). Most US patents listing Australian inventors have either an Australian inventor or assignee owning the patent (68% for medical and 81% for non-medical patents) (Box 3). The technology most likely to arise from another country is that owned by an assignee in another country and listing an inventor from another country. Thus, 15% of medical and 7% of non-medical patents in our study may have originated outside Australia (Box 3). Patents are either assigned, usually to an organisation, or unassigned (thus owned by the inventor). We found 82% of medical patents were assigned, compared with 69% of non-medical patents (P < 0.001, Box 2). For assigned patents, both medical and non-medical patents usually have one assignee (Box 2). For these assigned patents, there were three large differences, with medical patents being (Box 4): less likely to be owned by a business; four times more likely to be owned by a university; and 40 times more likely to be owned by a research institute. Both medical and non-medical patents are increasingly owned by business and universities, with fewer being unassigned. From 1984 to 1999, patents assigned to business increased from 49% to 63%; patents assigned to universities increased from 2% to 7%; and unassigned patents decreased from 36% to 20% of all patents. Medical patents were three times as likely as non-medical patents to quote from published scientific articles. Sixty per cent (785/1308) of medical patents cited one or more scientific publications, compared with only 23% (1475/6527) of non-medical patents (P < 0.001). Characteristics of medical patents Most of the 1785 medical inventors are not prolific, with 67% (1200/1785) listed only once in 1984-1999. About 18% (318/1785) of medical inventors are listed on three or more medical patents. However, the 17 most prolific medical inventors (Box 5) were responsible for 13% (169/1308) of Australian medical patents. Eleven of these prolific inventors are clustered around four different technologies: electromedical devices (cardiac pacemakers and cochlear ear implants), biosensors, ribozymes, and the relaxin gene. Just 14 organisations own 33% (438/1308) of medical patents; six of these organisations are Australian universities and their affiliated institutions (Box 6). Surprisingly, 20% (264/1308) of medical patents were owned by just five organisations: the University of Melbourne, Telectronics, the Commonwealth Scientific and Industrial Research Organisation (CSIRO), Biotech Australia, and the University of New South Wales. The three most common types of medical technologies are cardiac pacemakers (7%), syringes or parenteral drug delivery technology (4%), and cochlear ear implants (3%). Discussion Principal findings We believe that this is the first published report that has examined Australian medical patents in detail. Australia, like all countries of the Organisation for Economic Co-operation and Development (OECD), has shown a strong rise in the number of US patents granted per capita since the 1960s.5,16 However, Australia is still ranked a low 16 of 20 OECD countries,7 with only a modest increase in the proportion of utility patents granted to Australian inventors in the US during 1984-1999 (from 0.46% [309/67200] to 0.52% [800/153492]16). As expected, Australia's comparative technological advantage is found mainly in mining and agriculture. This is similar to other resource-abundant OECD countries like Canada, Finland and Norway.5,7 However, our study, along with others,7,17 indicates a shift in Australia to patenting in higher technologies. Our study suggests that medical technology, especially medical biotechnology, is an increasingly important part of Australia's intellectual property portfolio. This may explain why Australia appears to be developing a technological advantage in biotechnology and pharmaceuticals.17 To place this trend in a global perspective, our study would need to be repeated for other, especially OECD, countries. There is a dip in the total number of US patents granted to Australian inventors from 1990 to 1993 (Box 1), possibly reflecting the economic recession at the time. Interestingly, the trend in medical and medical biotechnology patents did not show this decrease, suggesting that development of such technology may be more resistant to downturns in the economy. Another feature was the 51% jump in the number of US patents granted to Australian inventors from 1997 to 1998 -- possibly a flow-on from the 54% increase in the number of patent applications filed by Australians in the US between 1994 and 199818 (noting that it usually takes two years from lodging a patent application until it is granted19). This trend coincides with increased research and development spending in Australia, particularly by business (which unfortunately declined in 1996-97).20 However, these changes may also reflect increased processing of patent applications by the US Patent and Trademark Office7 -- the overall number of utility patents issued jumping 32% from 111 983 in 1997 to 147 520 in 1998.16 Our study lends support to recent findings of the importance of university-based research in underpinning high-technology patents and industries.1,21 Universities and their affiliated institutions: make up more than a third of the most prolific patenting organisations; own an increasing proportion of US patents granted to Australian inventors; and are the source of 97% of the scientific articles cited in Australian medical patents.17 These findings could be the result of Australian governments actively encouraging universities to fund and commercialise research and develop links to industry. The CRCs were part of such initiatives, but the fact that only eight patents are owned by CRCs suggests that they are not very productive in commercialising research. However, this is difficult to judge, as the patents may be assigned to commercial or university partners. Our data also support the emerging ideas on the importance of clusters of co-located industries and universities where collaboration and competition act as constant spurs to innovation, such as is seen in Silicon Valley in California.21 In Australia, such clusters appear to be growing in Melbourne and Sydney for industries in biotechnology and electromedical devices. This is demonstrated by examining the prolific inventors and their assignees, indicating varied links between industry and publicly funded institutions. Strengths and weaknesses of the study Possible weaknesses in our study relate to three areas of potential misclassification in our patent data. Classification of country of origin: We classified patents as Australian if any inventor was an Australian resident. This may result in the inclusion of technology originating in another country but which had an Australian inventor working on it (estimated to be about 15% for medical and 7% for non-medical patents). Definition of medical patents: Given the absence of any published guidelines, it could be debated whether certain technologies are really "medical" (such as those related to optometry and sunscreen lotions) and whether dental technologies should have been excluded. Classification of assignees as "business": Assignees with a business-type suffix (ie, "Pty Ltd", "Ltd", "Corp", "Inc", "NV", "AG" and "GMBH"), unless detected through searches on the Internet as belonging to another category such as a technology transfer organisation, would have been misclassified as a business. It is difficult to predict whether the first two potential biases could alter our conclusions. The third may lead to an overestimation of the number of patents owned by business. When identifying the country of origin of a patent, the main convention is to use the residency of the inventor16,17 rather than assignees, partly because a large proportion of patents are unassigned (29% in our study). Like other technology or innovation indicators, patent statistics have advantages and disadvantages.22,23 Our study treats all patents as being of equal importance; however, a patent's commercial value can vary enormously.23,24 Furthermore, patent data do not capture all new technology, as some may not be patentable, and patenting can vary with economic conditions and with the strategic concerns of companies.23,24 For example, patenting as a means of protecting intellectual property is very important for the pharmaceutical industry but of little relevance to the rubber industry.24 In addition, the difficulty when describing patents owned by business is that many are granted under the names of subsidiaries and divisions that are different from the names of parent companies. Some companies even actively hide emerging technologies under different company names, so-called "submarine" patents.5,25 Possible mechanisms and implications for policymakers Australia has a substantial and growing trade deficit in high-technology goods,21 making it more imperative to capture more of the economic value of Australian medical patents. But how? First, the more prolific medical inventors and their organisations could be canvassed when developing government policy which may impact on the commercialisation of medical technology. Such surveys could also identify emerging technologies, which may be the basis of new industries, enabling government to take an anticipatory stance on industry policy. Second, the medical inventors and assignees could be actively targeted with assistance in developing their medical technology. To foster the growing culture of enterprise and innovation within academia,4 it may be worth considering a reward for the prolific inventors and assignees. Such rewards may encourage other inventors and promote inventors as role models for other scientists. Acknowledgements We are grateful to Associate Professors Sam Garrett-Jones and Tim Turpin from the Centre for Research Policy at the University of Wollongong for providing the database of Australian patents in the US for 1984-1994, and to Ms Christine Porter, Manager of the European and Commonwealth Office, Community of Science, for providing free access to the US patents on their website. We would like to thank Dr Dora Marinova from ISTP at Murdoch University and Professor Jane Marceau, Pro Vice Chancellor (Research) at the University of Western Sydney Macarthur, for their valuable advice. Eugen Mattes was the recipient of an Eva K A Nelson Medical Research Scholarship from the University of Western Australia from 1995 to 1998 and an advanced academic registrar funded by the Royal Australian College of General Practitioners in 1999 and the Registrar Scholarship and Research Fund of the College in 2000. We also want to acknowledge the support of Professor Max Kamien and the Department of General Practice, University of Western Australia. We would also like to thank the reviewers for their helpful comments. References Wills PJ (Chairman). Health and Medical Research Strategic Review. The virtuous cycle: working together for health and medical research. Canberra: Department of Health and Aged Care, 1999. The National Innovation Summit. <http://www.isr. gov.au/industry/summit/index.html> Accessed 24 February 2000. Biotechnology Australia. Developing Australia's biotechnology future. Discussion Paper. Canberra: Commonwealth of Australia, 1999. Mercer D, Stocker J (Steering Committee). Review of greater commercialisation and self funding in the Cooperative Research Centres Programme. Canberra: Department of Industry, Science and Tourism, 1998. Patel P, Pavitt K. Australia's technological capabilities: an analysis using US patenting statistics. Brighton: Science Policy Research Unit, University of Sussex, 1995. Bertin G, Wyatt S. Multinationals and industrial property: the control of the world's technology. Hemel Hempstead, Hertfordshire, England: Harvester-Wheatsheaf, 1988. Department of Industry, Science and Technology (DIST). Australian business innovation: a strategic analysis. Report No. 5. Canberra: AGPS, 1996. CHI Research Inc. <http://www.chiresearch.com/> Accessed 7 February 2000. Community of Science. US patents. <http://patents.cos.com/> Accessed 10 July 2000. US Patent and Trademark Office. USPTO Web Patent Database. <http://www.uspto.gov/patft/index.html> Accessed 7 February 2000. Intellectual Property Network. <http://www. delphion.com/home> Accessed 7 December 2000. National Science and Technology Council. Biotechnology for the 21st Century: New Horizons. Washington: USGPO, 1995. Available at <http://www.nal.usda.gov/bic/bio21>. Microsoft Excel 97 SR-2 [computer program]. Cambridge, Massachusetts: Microsoft, 1997. Dogpile. <http://www.dogpile.com/> Accessed 7 February 2000. SPSS for Windows [computer program]. Version 8.0. Chicago, Illinois: SPSS Inc, 1997. Patent counts by country/state and year. Utility patents. January 1, 1963 - December 31, 1999. Technology Assessment and Forecast (TAF) Program, Office for Patent and Trademark Information, US Patent and Trademark Office. <http://www.uspto.gov/web/offices/ac/ido/oeip/taf/ cst_utl.pdf> Accessed 10 July 2000. Narin F, Albert M, Kroll P, Hicks D. Inventing our future: the link between Australian patenting and basic science. <http://www.arc.gov.au/ publications/arc_pubs/00_02.pdf> Accessed 30 October 2000. Number of utility patent applications filed in the United States, by country of origin, calendar years 1965 to present. Technology Assessment and Forecast (TAF) Program, Office for Patent and Trademark Information, US Patent and Trademark Office. <http://www.uspto.gov/web/offices/ac/ido/oeip/taf/ appl_yr.pdf> Accessed 30 October 2000. Trilateral Statistical Report 1997. US Patent and Trademark Office. <http://www.uspto.gov/web/offices/ dcom/olia/trilat/tsr97/> Accessed 10 July 2000. Science and Technology Policy Branch of the Department of Industry, Science and Resources. Australian science and technology at a glance 2000. <http://www.isr.gov.au/science/analysis/glance2000/> Accessed 30 October 2000. Marceau J, Manley K, Sicklen D. The high road or the low road? Alternatives for Australia's future. Sydney: Australian Business Foundation; 1997. Patel K, Pavitt K. Paterns of technological activity: their measurement and interpretation. In: Stoneman P, editor. Handbook of the economics of innovations and technical change. Oxford: Blackwell, 1995; 14-51. Industry Analysis Branch of the Department of Industry, Science and Resources. Measuring the knowledge-based economy. How does Australia compare? Canberra: Commonwealth of Australia, 1999. Geroski P. Markets for technology: knowledge, innovation and appropriability. In: Stoneman P, editor. Handbook of the economics of innovation and technical change. Oxford: Blackwell, 1995; 90-131. Garrett-Jones S, Aylward D. Measuring linkages between basic scientific research and Australian industrial technologies using patent data. Wollongong: Centre for Research Policy, University of Wollongong, 1995. (Received 14 Jul, accepted 2 Nov, 2000) Authors' details University of Western Australia, Perth, WA. Eugen Mattes, MB BS, MPH, Advanced Academic Registrar, Department of General Practice, and PhD Scholar, Department of Surgery, Fremantle Hospital; Michael C Stacey, DS, FRACS, Associate Professor, Department of Surgery. Reprints will not be available from the authors. Correspondence: Dr E Mattes, Visiting Research Fellow, TVW Institute for Child Health Research, Division of Population Sciences, 100 Roberts Road, Subiaco, WA 6008. emattesATcyllene.uwa.edu.au Make a comment 1: Number of utility patents granted in the United States to Australian-resident inventors from 1984 to 1999 Back to text 2: The number of medical and non-medical patents granted in the United States to Australian-resident inventors between 1984 and 1999, and numbers of inventors and assignees (owners) Medical Non-medical Total Patents 1308 6527 7835 Inventors Number listed Number of individuals Inventors/patent (median)* 3270 1785 2 11127 7092§ 1 14397 8744¶ Assigned patents† 1068 (82%) 4533 (69%) 5601 Assignees Number listed Number of individual assignees‡ Assignees/assigned patent (median)* 1192 448 1 4909 2309 1 6101 2701¶ * The medians were significantly different (Mann-Whitney U test; P < 0.003). For assignees this is unlikely to be of practical significance. † Medical and non-medical groups are significantly different (Pearson χ2, P < 0.001). ‡After correcting errors or differences in spelling (16% of medical and 9% of non-medical assignees were either misspelt or spelt differently). § Calculated using ratio from medical patents: there were 1785 individual medical inventors after correcting the spelling of the initial list of 1878 individuals. So, for non-medical inventors, it was estimated that there were 7092=7461 x (1785/1878) individuals, assuming a similar 5% difference in spelling of the 7461 non-medical inventors listed initially. ¶Not equal to the sum of inventors or assignees on medical and non-medical patents, as 133 inventors and 56 assignees are on both types of patents. Back to text 3: The location of inventors and assignees for United States patents listing Australian inventors for 1984-1999 Location of inventors Location of assignees Medical Non-medical Australia Unassigned patents* Australia Australia and other countries Other countries* Subtotal 226 (17%) 660 (50%) 8 (1%) 139 (11%) 1035 (79%) 1942 (30%) 3357 (51%) 74 (1%) 505 (8%) 5878 (90%) Australia and other countries (international collaboration) Unassigned patents Australia* Australia and other countries* Other countries* Subtotal 14 (1%) 48 (4%) 22 (2%) 191 (15%) 275 (21%) 52 (1%) 114 (2%) 40 (1%) 443 (7%) 649 (10%) Total 1308 (100%) 6527 (100%) Global Pearson χ2 is significant (P <0.001.). * Significant difference between medical and non-medical patents (P <0.001). Back to text 4: Classifications of assignees listed on the 1068 medical and 4533 non-medical assigned US patents listing Australian-resident inventors for 1984-1999 Assignee Medical patents Non-medical patents Business* University* Research institute* Government* CSIRO Individual* Technology transfer organisation Non government organisation† Cooperative research centre Total 700 (59%) 206 (17%) 97 (8%) 70 (6%) 60 (5%) 30 (2.5%) 22 (1.8%) 6 (0.5%) 1 (0.1%) 1192 (100%) 3913 (80%) 181 (4%) 8 (0.2%) 195 (4%) 272 (6%) 257 (5%) 69 (1%) 7 (0.1%) 7 (0.1%) 4909 (100%) Global Pearson χ2 is significant (P <0.001). Pairwise comparisons were done using Pearson χ2, except where Fisher's exact test was needed when an expected count was less than 5. *Significant difference between medical and non-medical patents (P <0.004). †Significant difference between medical and non-medical patents (P=0.027). CSIRO=Commonwealth Scientific and Industrial Research Organisation. Back to text 5: The 17 most prolific Australian medical inventors listed on 10 or more Australian medical patents in the US for 1984-1999, grouped by technology Main technology Inventor Number of patents Main assignees Method for constructing proteins and other molecules Simpson R 18 Ludwig Institute for Cancer Research, US Cardiac pacemakers and cochlear ear implants Money D Kuzma J Daly C Milijasevic Z 15 12 10 10 Telectronics Pty Ltd, NSW, and Cochlear Pty Ltd, NSW Biosensors Cornell B Braach-Maksvytis V Raguse B 14 13 10 Australian Membrane and Biotechnology Research Institute, NSW Ribozymes - gene shears Jennings P Cameron F 14 (1) 11 Gene Shears Pty Ltd, NSW and ACT Vitamin B12 as carrier for oral drugs Russell-Jones G 14 (1) Biotech Australia Pty Ltd, NSW Intraocular lenses Barrett G 13 Alcon Laboratories Inc, and Chiron, US, and Oversby Pty Ltd, WA Relaxin gene Tregear G Niall H 13 (1) 10 (1) Howard Florey Institute, VIC Syringe or drug infusion devices Whisson M 12 Eastland Technology Australia Pty Ltd, WA Matrix metalloprotease inhibitors Grobelny D 10 Glycomed Inc, US, and Narhex Ltd, Hong Kong Contact lenses Meijs G 10 (6) CIBA Vision Group, US Back to text 6: The most prolific assignees listed on 15 or more Australian medical patents in the United States for 1984-1999 Assignee Medical Non-medical Total University of Melbourne and affiliated institutions 76 28 104 Telectronics NV or Telectronics Pty Ltd or Telectronics Pacing Systems Inc 75 0 75 CSIRO 60 272 332 Biotech Australia Pty Ltd 28 3 31 University of New South Wales and affiliated institutions 25 51 76 Australian National University and Anutech Pty Ltd 23 30 53 University of Sydney 22 26 48 Monash University and affiliated institutions 21 8 29 AMRAD Corp Ltd 21 3 24 Ludwig Institute for Cancer Research* 21 0 21 University of Queensland and Queensland Institute of Medical Research (QIMR) Council 20 18 38 Cochlear Pty Ltd 16 0 16 Commonwealth of Australia 15 87 102 Gene Shears Pty Ltd 15 0 15 Total 438 526 964 *16 of the 21 patents originated from the Melbourne branch (Dr C Thumwood, Scientific Administrator, Ludwig Institute for Cancer Research, personal communication). 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Eugen Mattes · Michael C Stacey

Clinical Practice A primer of complementary and alternative medicine commonly used by cancer patients Edzard Ernst MJA 2001; 174: 88-92 Abstract - Acupuncture - Diets - Aromatherapy - Chiropractic - Coffee enemas - Herbal medicinal products - Homoeopathy - Meditation - Ozone therapy - Shark cartilage - Spiritual healing - Comment - References - Author's details - - More articles on complementary medicine Abstract Complementary and alternative medicine (CAM) is frequently used by cancer patients, and many oncologists have limited knowledge of CAM. This article provides a brief, evidence-based introduction to several CAM treatments relevant in the context of cancer. "Alternative" diets, chiropractic, coffee enemas, ozone therapy, and shark cartilage seem to have little to offer cancer patients. The evidence for or against homoeopathy and spiritual healing is at present inconclusive. Acupuncture, aromatherapy, and meditation may be useful for nausea/vomiting, for mild relaxation, and for pain/anxiety, respectively. Herbal treatments offer no reasonable prospect of a cure (mistletoe), but could be useful as palliative treatments (eg, for depression [St John's wort] or anxiety [kava]). Our knowledge regarding the potential benefit and harm of CAM is insufficient. The prevalence of use of complementary and alternative medicine (CAM) for treating cancer is high: a systematic review of all surveys published by 1998 indicated an average prevalence of 34%,1 a figure which is close to that observed for Australia,2 but markedly lower than the 75% reported recently in the United States.3 Cancer patients generally report satisfaction with CAM1,2 and rarely inform their doctors about their CAM use.4 Consequently, many oncologists have limited knowledge of the subject.5My aim is to provide a brief introduction to those CAM modalities which have been identified as most relevant:1-5 acupuncture, "alternative" cancer diets, aromatherapy, chiropractic, coffee enemas, herbal medicinal products (HMPs), homoeopathy, meditation, ozone therapy, shark cartilage, and spiritual healing. Particular emphasis is placed on reliable evidence (eg, randomised clinical trials, or systematic reviews and meta-analyses of such studies) regarding safety and effectiveness. It is important to note that this article is not a systematic review of all available data. Acupuncture Acupuncture constitutes one of several elements of Traditional Chinese Medicine (TCM). Advocates of TCM view ill health as an imbalance of the life force "Qi", which is believed to flow in channels called meridians. To restore the balance (and thus health), the flow of Qi can be influenced by stimulating acupuncture points located along meridians. Typically, this is done by inserting needles, but heat (moxibustion), external pressure (acupressure), electrical currents (electroacupuncture), laser (laser acupuncture), and other stimuli are also used.6 Acupuncture is one of the best-known forms of CAM.7 Several hundred controlled clinical trials of acupuncture for a range of conditions have been published (for a review, see ref. 6). Such trials face formidable methodological challenges (eg, blinding or controlling for placebo effects), an issue that also applies to many other CAM treatments. Often the results of individual studies are contradictory. Thus, systematic reviews (including meta-analyses) of the totality of the trial data present the least-biased assessment. Box 1 provides an overview of the conclusions from all systematic reviews and meta-analyses of acupuncture currently available.6 There is good evidence for the use of acupuncture for non-specific back pain, dental pain, migraine, and nausea/vomiting. Of these conditions, only nausea and vomiting are directly relevant to cancer patients. There are many conditions for which substantial uncertainty remains (in spite of the availability of clinical trials) (Box 1), and future trials are required to define the effectiveness of acupuncture in these situations. Serious risks of acupuncture pertain mainly to tissue trauma (eg, pneumothorax) and infections (eg, hepatitis). They are usually avoidable and extremely rare.8 Less serious adverse effects (eg, pain of needle insertion or minor bleeding at the site of insertion) are much more common but transient.9 "Alternative" cancer diets More than 40 different cancer diets have been claimed to prevent and/or treat cancer.10 Several of these diets are an extension of conventional medicine, whereas others are considered more in the realm of CAM. The diets typically emphasise avoiding meat, and many are strictly vegetarian. Compelling evidence is largely absent. Two diets deserve particular mention. The Gerson diet is basically a vegan form of nutrition. Patients consume the juices of about 9 kg of fruit and vegetables per day (primarily carrots and apples). The diet is often supplemented with coffee enemas. The "Gerson Institute" offers anecdotal evidence of success in its promotional literature, and a retrospective analysis11 of 153 melanoma patients suggested an impressive prolongation of the five-year survival rates of Gerson patients compared with patients in orthodox care. This study was retrospective, its sample size was small, and about a third of all patients were lost to follow-up. Bias was further introduced by use of a self-selected sample, and through the use of non-randomised controls. The Macrobiotic diet is based on the belief that cancer is caused by an imbalance of yin and yang. It is assumed that imbalances can be corrected by eating foods with either yin or yang qualities. The Macrobiotic diet is composed primarily of whole-grain products (50%-60%) and fresh vegetables (20%-40%). Meat and milk are not allowed, but small amounts of fish are permitted. Macrobiotic diets allow few fluids but they require large amounts of salt intake (about 30 g/day). There is no clinical evidence to suggest that this diet prevents, alleviates or cures cancer.12 There are positive aspects to some cancer diets (eg, a reduction in red meat consumption, increase in intake of fruit, vegetables and fibre). However, dogmatic adherence to an unbalanced diet is clearly counterproductive and some CAM cancer diets (eg, Gerson, Macrobiotic, strict vegan) carry the risk of malnutrition. Aromatherapy Aromatherapy is the medicinal use of concentrated volatile oils extracted from plants.13 The term was first used in 1936 by the French chemist Gattefossé.14 Today it usually implies gentle massage therapy with a range of aromatic plant extracts known as essential (ie, volatile) oils.15 A recent systematic review summarised all randomised controlled trials (RCTs) testing the clinical effectiveness of aromatherapy.16 Twelve trials were found; six of them had no independent replication and six related to the relaxing effects of aromatic oils applied through gentle massage. These studies suggest that aromatherapy massage has mild and transient anxiolytic activity. Even though the effects are likely to be small, they may have benefits for cancer patients in terms of enhancing feelings of wellbeing. There are few risks associated with aromatherapy. Although some oils are potentially carcinogenic,17 the exposure rate for patients (but perhaps not for therapists) is probably too low to constitute a real danger. Chiropractic Chiropractic is "a system of health care founded in 1895 by Daniel David Palmer which is based on the belief that the nervous system is the most important determinant of a person's state of health; according to chiropractic theory, most diseases are the result of 'nerve interference', caused by spinal subluxations, which respond to spinal manipulation".13 Chiropractors employ spinal manipulation (eg, high-velocity thrusts), mobilisation (eg, low-velocity techniques), and other forms of natural medicine. A systematic review of conservative treatments for neck pain/headache failed to show convincingly that chiropractic is more effective than other interventions.18 A meta-analysis of chiropractic for low back pain published in 199219 suggested that chiropractic is effective for acute low back pain. For chronic low back pain, the evidence was less convincing. A more recent and more rigorous systematic review concluded that "the available randomised clinical trials provided no convincing evidence of the effectiveness of chiropractic for acute or chronic low back pain".20 Owing to lack of data, no firm conclusions are possible for the effectiveness of chiropractic for other conditions. One exception is asthma, where two rigorous, sham-controlled RCTs showed that chiropractic is no more effective than sham interventions.21,22 There is no evidence that chiropractic alleviates symptoms related specifically to cancer. About 50% of patients treated by chiropractors will experience mild and transient adverse effects, mostly local or distant pain lasting for one or two days.23,24 Serious complications of chiropractic are probably rare events that occur predominantly after manipulation of the cervical spine. A recent review described 32 fatalities associated with upper spinal manipulation.25 In addition, significant indirect risks are on record. Examples are the overuse of x-rays by some chiropractors26 and their tendency to advise against vaccination.27 Coffee enemas Coffee enemas are a derivative of colon therapy (ie, water enemas).28 As part of the Gerson diet,11 coffee enemas are usually administered on a four-hourly basis "to help relieve pain, nausea and other symptoms accompanying detoxification".29 Proponents claim that caffeine is absorbed in the colon, leading to vasodilatation of the liver, which in turn enhances the process of elimination of "toxins".29 These assumptions are unproven. There is no reliable evidence of the clinical efficacy of coffee enemas for any indication. Coffee enemas are regularly associated with adverse reactions (eg, electrolyte imbalances), some of which are severe.30 On balance, therefore, no reasons exist for recommending coffee enemas to cancer patients. Herbal medicinal products With many medicinal plants, it is not possible to define the principal active constituents; the clinical effects of most HMPs are produced by more than one active compound, and in many instances the full range has not been identified. Thus, the conventional pharmacological wisdom of isolation and synthesis of (single) active ingredients is often not a viable option. Several traditions of herbal medicine (eg, Traditional Chinese Medicine, Ayurveda) typically use complex, often individualised, mixtures of several (sometimes more than 20) medicinal herbs in one single prescription. However, most modern self-prescribed HMPs consist of one single herb. Several such HMPs have been submitted to relatively extensive clinical tests. Box 2 provides an overview of HMPs for which sufficient trial data as well as systematic reviews or meta-analyses exist (for a review, see ref. 31). It is obvious that each HMP (for each indication) has to be evaluated on its own merit -- generalisations regarding the efficacy (and safety) of HMPs are nonsensical. For other HMPs, efficacy remains uncertain. Mistletoe (Viscum album) is often recommended as a treatment for cancer. It gained widespread popularity in Europe, which now also extends to the US and Australia. Its proponents claim that it arrests or delays tumour progression and improves quality of life. Mistletoe lectins have been shown repeatedly to exhibit antineoplastic activity.32 However, a systematic review of all 11 controlled clinical trials yielded disappointing results.33 The average methodological quality of the primary studies was poor. The results of most trials favoured mistletoe, but the most rigorous study did not demonstrate efficacy. The authors therefore concluded that they "cannot recommend the use of mistletoe extracts in the treatment of cancer patients with an exception for patients involved in clinical trials".33 Since the publication of that report, several new studies have emerged, but the overall conclusion has not become more positive.34 Homoeopathy Homoeopathy is based on two highly controversial principles: the law of "similars" (ie, like cures like), and the notion that highly "potentised" (diluted) remedies can be effective, even though they are unlikely to contain a single molecule of the original substance. Scientists insist that where there is no molecule there can be no effect; all clinical effects of homoeopathy, they maintain, must therefore be due to placebo. A meta-analysis of all 123 randomised or placebo-controlled trials concluded that the clinical effects of homoeopathy are not entirely due to placebo.35 This meta-analysis has been criticised for pooling data relating to all types of indications and remedies. It may therefore be relevant to assess defined indications and remedies and see what evidence for or against homoeopathy emerges. The remedy that has been submitted to more controlled clinical trials than any other homoeopathic medicine is Arnica montana (a plant-based homoeopathic remedy often used for alleviating bruising and other tissue trauma). Two independent systematic reviews of all studies of homoeopathic arnica provided no conclusive evidence that it is clinically more effective than placebo.36,37 The condition most frequently employed for testing the efficacy of homoeopathic remedies is delayed-onset muscle soreness. A systematic review of all relevant trials produced no convincing evidence that homoeopathic remedies are superior to placebo in treating this condition.38 In their daily routine, homoeopaths are more likely to aim at alleviating ailments like asthma or headaches; systematic reviews found no good evidence to suggest that homoeopathic remedies are efficacious for either of these conditions.39,40 Most homoeopaths would claim that their approach can alleviate symptoms associated with cancer and therefore has a role in supportive/palliative care. Reliable evidence to substantiate this claim is lacking. Highly diluted homoeopathic drugs are obviously devoid of adverse effects, but low dilutions may cause adverse effects (eg, allergic reactions). Homoeopaths claim that, in about 20% of all patients, they would see an acute clinical deterioration ("homoeopathic aggravation") if the optimal remedy has been administered. Such aggravations might constitute a safety issue in their own right. Finally, some non-medically qualified homoeopaths advise their clients against vaccination,37 which clearly constitutes an indirect risk of homoeopathy. Meditation Meditation is a general term describing treatments in which a person empties his/her mind of extraneous thought with the intent of elevating the mind to a different level and transcending mundane concerns.13 A wide array of techniques exist which fall into two broad categories: emphasis on concentration (eg, Transcendental Meditation) and emphasis on mindfulness (eg, Vipassana). The techniques can be learned from experienced teachers during a series of tutored sessions. The physiological effects of meditation are those of deep relaxation. A typical relaxation response includes the cardiovascular (eg, decrease in blood pressure and heart rate) and the endocrine (eg, decrease in stress hormones) systems. There is evidence from controlled clinical trials suggesting that these effects can be used clinically to control cardiovascular risk factors, chronic pain and anxiety,41 which could be of benefit to cancer patients. Potential adverse effects of meditation include psychological symptoms such as tension, anxiety, depression, and confusion. A syndrome termed "meditation sickness" has been recognised.13 Meditation is contraindicated in patients with psychotic or borderline personality disorders.41 Ozone therapy Several techniques of administering ozone are being promoted as a treatment for cancer.42 The "optimal" system is apparently via the exposure ex vivo of up to 300 mL of freshly drawn blood to a gas mixture of oxygen and ozone, followed by reinfusion of this blood into the patient.43 Numerous mechanisms of action are quoted in support of ozone therapy. However, few rigorous clinical trials of the treatment exist. Those that have been published demonstrated no evidence of effect.44,45 The risks of ozone therapy are played down by its proponents.42,43 Yet, numerous reports of serious complications, including hepatitis, and at least five fatalities have been reported.46,47 Until more positive evidence emerges, ozone therapy should be avoided. Shark cartilage Shark cartilage is perhaps the most widely promoted CAM "cancer cure" in recent years. In 1995, the annual world market for shark cartilage products exceeded US$30 million.48 Two glycoproteins (sphyrnastatin 1 and 2) have been isolated from the cartilage of the hammerhead shark and were reported to have strong antiangiogenic activity inhibiting tumour neovascularisation,49 an effect which could be helpful in human cancer therapy. However, as macromolecules are not usually absorbed by the intestinal tract, it is questionable whether the sphyrnastatins ever reach the bloodstream in sufficiently high concentrations. To date, no controlled clinical studies testing the efficacy of shark cartilage have been published. Preliminary results have been reported from a US trial: 50% of cancer patients who took 100 mg dried cartilage powder daily reported improvements in quality of life, appetite and relief of pain.50 More recently, a well-documented trial was published.51 Sixty patients with various advanced cancers received 1 g/kg shark cartilage daily for 12 weeks. No complete or partial responses were noted, and the authors conclude that "shark cartilage as a single agent was inactive in patients with advanced-stage cancer and had no salutary effect on quality of life".51 Spiritual healing Spiritual healing has been defined as the direct interaction between one individual (the healer) and a patient, with the intention of improving the patient's condition or curing the illness.52 Treatment can occur through personal contact or at a (sometimes large) distance. Several variations exist (eg, therapeutic touch, Reiki, faith healing, intercessory prayer), and therapists of one group see themselves as distinct from other groups. Spiritual healers, who are usually not medically qualified, believe that the therapeutic effect results from the channelling of "energy" from an undefined source via the healer to the patient; there is no evidence that this energy actually exists. The central claim of healers is that they promote or facilitate self-healing and wellbeing, both of which could be relevant to cancer patients. The evidence from randomised controlled trials of all distant healing approaches on human patients is highly conflicting. A systematic review of 23 randomised and adequately controlled clinical trials found that about half of these trials suggested that healing is effective (ie, better than control interventions). Yet methodological shortcomings prevented firm conclusions.53 As long as it is not used as an alternative to effective therapies, spiritual healing should be virtually devoid of risks. Comment It has to be stressed again that this article is a mere primer and not an in-depth analysis of the existing evidence. CAM includes several hundred treatments. Because of the obvious constraints of space only 11 were discussed briefly. Inevitably, other important treatments (eg, osteopathy, hypnotherapy, naturopathy) had to be omitted. Much of the above evidence indicates that CAM, even though used frequently by cancer patients, is not supported by compelling data. This is particularly true for CAM as a cancer cure. The role of CAM as a palliative or supportive cancer treatment might be slightly different.54 Several CAM modalities have the potential to increase wellbeing with little potential for harm (eg, acupuncture, reflexology). This raises the complex question of what evidence is required for such therapies. Is it enough that individual patients desire CAM and feel better with it, or does one need to demonstrate that the CAM intervention in question is at least as effective and/or cost-effective as conventional palliative care? These questions require serious consideration and further, detailed discussion. The potential for harm is considerable for several of the CAM treatments (eg, chiropractic, coffee enemas, ozone therapy, HMPs). Ideally, one would want exact incidence figures of adverse events and conduct proper risk-benefit analyses. Unfortunately, for most forms of CAM, such data are not available. Future research should focus not merely on the efficacy but also on the safety of CAM. The ultimate question that needs answering is, does a given CAM intervention do more good than harm to cancer patients? In conclusion, cancer patients frequently use CAM. For most of these treatments the evidence is woefully incomplete. One challenge for the future is to adequately match CAM's popularity with an evidence base. References Ernst E, Cassileth BR. The prevalence of complementary/alternative medicine in cancer. Cancer 1998; 83: 777-782. Begbie SD, Kerestes ZL, Bell DR. Patterns of alternative medicine use by cancer patients. Med J Aust 1996; 165: 545-548. Morris KT, Johnson N, Homer L, Deb W. A comparison of complementary therapy use between breast cancer patients and patients with other primary tumor sites. Am J Surg 2000; 179: 407-411. Kao GD, Devine P. Use of complementary health practices by prostate carcinoma patients undergoing radiation therapy. Cancer 2000; 88: 615-619. Newell S, Sanson-Fisher RW. Australian oncologists' self-reported knowledge and attitudes about non-traditional therapies used by cancer patients. Med J Aust 2000; 172: 110-113. Ernst E, White A. Acupuncture: a scientific appraisal. Oxford: Butterworth Heinemann, 1999. Eisenberg DM, David RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997. JAMA 1998; 280: 1569-1575. Ernst E, White A. Life-threatening adverse reactions after acupuncture? A systematic review. Pain 1997; 71: 123-126. White A, Ernst E. survey of adverse events following acupuncture (SAFA). Forsch Komplementärmed 2000; 7: 56. Ernst E, Cassileth B. Cancer diets, fads and facts. Cancer Prevent Int 1996; 2: 181-187. Hildenbrand G. Five-year survival rates of melanoma patients treated by diet therapy after the manner of Gerson: a retrospective review. Altern Ther Health Med 1995; 4: 29-37. Bowman BB, Kushner RF, Dawson SC, Levin B. Macrobiotic diets for cancer treatment and prevention. J Clin Oncol 1984; 2: 702-711. Segen JC. Dictionary of alternative medicine. Stamford, US: Appleton Lange, 1998; 81. Gattefossè R-M. Aromatherapy. Paris: C W Daniel Co Ltd, 1993. Vickers A, Zollman C. ABC of complementary medicine massage therapies. BMJ 1999; 319: 1254-1257. Cooke B, Ernst E. Aromatherapy: a systematic review. Br J Gen Pract 2000; 50: 493-496. Tisserand R, Balacs T. Essential oil safety. Edinburgh: Churchill Livingstone, 1995. Aker PD, Gross AR, Goldsmith CH, Peloso P. Conservative management of mechanical neck pain: systematic overview and meta-analysis. BMJ 1996; 313: 1291-1296. Shekelle PG, Adams AH, Chassin MR, et al. Spinal manipulation for low back pain. Ann Intern Med 1992; 117: 590-598. Assendelft WJJ, Koes BW, van der Heijden GJMG, Bouter L. The effectiveness of chiropractic for treatment of low back pain: an update and attempt at statistical pooling. J Ther Physiol Ther 1996; 19: 499-507. Nielsen NH, Bronfort G, Bendix T, et al. Chronic asthma and chiropractic spinal manipulation: a randomized clinical trial. Clin Exper Allergy 1995; 25: 80-88. Balon J, Aker PD, Crowther ER, et al. A comparison of active and simulated chiropractic manipulation as adjunctive treatment for childhood asthma. New Engl J Med 1998; 339: 1013-1020. Leboeff-Yde C, Hennius B, Rudberg E, et al. Side effects of chiropractic treatment: a prospective study. J Manip Physiol Ther 1997; 20: 511-515. Senstad O, Leboeuf-Yde C, Borchgrevink C. Frequency and characteristics of side effects of spinal manipulative therapy. SPINE 1997; 22: 435-441. Di Fabio RP. Manipulation of the cervical spine: risks and benefits. Phys Ther 1999; 79: 50-65. Ernst E. Chiropractors' use of X-rays -- Correspondence. Br J Radiol 1998; 71: 897-900, 1107-1108. Ernst E. The attitude against immunisation within some branches of complementary medicine. Eur J Paediatr 1997; 156: 513-515. Ernst E. Colonic irrigation and the theory of autointoxication: a triumph of ignorance over science. J Clin Gastroenterol 1997; 24: 196-198. Petton R, Overholster L. Alternative cancer therapy. New York: Simon and Schuster, 1994. Green S. A critique of the rationale for cancer treatment with coffee enemas and diet. JAMA 1992; 68: 3224-3226. Ernst E. Herbal medicine. A concise overview for professionals. Oxford: Butterworth Heinemann, 2000. Beuth J. Clinical relevance of immunoactive mistletoe lectin-l. Anti-Cancer Drugs 1997; 8: S53-S55. Kleijnen J, Knipschild P. Mistletoe treatment for cancer: review of controlled trials in humans. Phytomedicine 1994; 1: 255-260. Ernst E. Mistletoe for cancer? Eur J Cancer 2001. In press. Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet 1997; 350: 834-843. Ernst E, Pittler MH. The efficacy of homoeopathic Arnica. A systematic review of placebo-controlled clinical trials. Arch Surg 1998; 133: 1187-1190. Lüdtke R, Wilkens J. Klinische Wirksamkeitsstudien zu Arnica in homöopathischen Zubereitungen. In: Albrecht H, Frühwald M, editors. Jahrbuch Band 5 (1998) Karl und Veronica Carstens-stiftung. KVC Verlag Essen, 1999; 97-112. Ernst E, Barnes J. Are homoeopathic remedies effective for delayed-onset muscle soreness? A systematic review of placebo-controlled trials. Perfusion 1998; 11: 4-8. Linde K, Jobst KA. Homoeopathy for chronic asthma. Cochrane Library 1998; 1: 1-7. Ernst E. Homoeopathic prophylaxis of headaches and migraine? A systematic review. J Pain Symptom Manage 1999; 18: 353-357. Astin J, Shapiro SL, Schwartz GER. Meditation. In: Novey DW, editor. Clinician's complete reference to complementary and alternative medicine. St Louis: Mosby, 2000; 73-85. Beck EG, Wasser G, Viebahn-Hänsler R. Der aktuelle Stand der Ozontherapie -- Empirie und Grundlagenforschung. Forsch Komplementärmed 1998; 5: 61-75. Bocci V. Ozone: a mixed blessing. Forsch Komplementärmed 1996; 3: 25-33. Kraft K, Stenkamp E, Vetter H. Effect of autohemotherapy with ozone cardiovascular risk factors in mildly hypertensive patients. Forsch Komplementärmed 1995; 2: 352. Diehm C, Rechsteiner HJ. Wer heilt hat Recht? Munich: Zuckschwerdt, 1987; 8-39. Schmitt H. Zur Ozontherapie. Med dissertation. University of Marburg, 1982. Gabriel C. Transmission of hepatitis C by ozone enrichment of autologous blood. Lancet 1996; 347: 541. Holt S. Shark cartilage and neutriceutical update. Alt Compl Ther 1995; 1: 414-416. Lee A, Langer R. Shark cartilage contains inhibitors of tumor angiogenesis. Science 1983; 221: 1185-1187. Mathews J. Media feeds frenzy over shark cartilage as cancer treatment. J Natl Cancer Inst 1993; 85: 1190-1191. Miller DR, Anderson GT, Stark JJ, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 1998; 16: 3649-3655. Hodges RD, Scofield AM. Is spiritual healing a valid and effective therapy? J R Soc Med 1995; 88: 203-207. Astin JA, Ernst E, Harkness EF. The efficacy of "Distant Healing": a systematic review of randomized trials. Ann Intern Med 2000; 132: 903-910. Ernst E, Cassileth BR. How useful are unconventional cancer treatments? Eur J Cancer 1999; 35: 1608-1613. Authors' details School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, UK. Edzard Ernst, PhD, FRCP(Edin), Professor, Department of Complementary Medicine. Reprints: Professor E Ernst, Department of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, 25 Victoria Park Road, Exeter EX2 4NT, UK. E. ErnstATexeter.ac.uk Make a comment Back to text Back to text

Edzard Ernst