No evidence supporting the use of individualised herbal medicine in any indication

Introduction

Most clinical trials of herbal medicine have focused on either standardised extracts of single herbs or standardised formulae. Evidence from such studies cannot be generalised to individualised herbal medicine, in which patients receive tailored prescriptions comprising a mixture of herbs. The individualised approach is emphasised in practitioner-based European medical herbalism, Chinese herbal medicine and Ayurvedic herbal medicine. The non-standardised nature of individually prepared herbal prescriptions and the consequent increased potential for adverse events and negative interactions means that safety and effectiveness need to be firmly established before such practices can be endorsed. We therefore carried out a systematic review of RCTs for the effectiveness of individualised herbal medicine in any indication. This review is particularly pertinent because section 12(1) of the Uk’s Medicines Act relating to regulation of unlicensed herbal remedies made up to meet the needs of individual patients is presently under review.

Methods

We searched for RCTs of any form of individualised herbal medicine in any indication in electronic databases (Medline, Embase, Cochrane Library, Cinahl, Amed) from inception to February 2007 using the search algorithm: [Individual$ OR tailored OR personal$ OR standard$ OR herbal$] AND [kampo OR herb$ OR plant$ OR Phyto$ OR botanic$ OR extract$ OR (traditional OR Chinese OR herbal OR oriental ADJ medicine)]. No language restrictions were imposed. Additional studies were sought by searching the reference lists of identified trials and reviews, contacting experts in the field who have published similar studies of herbal medicine (n = 5), contacting professional bodies of herbal medicine practitioners and by hand searching all back issues of FACT. The following 15 professional bodies were contacted: European Herbal Practitioners Association (EHPA); The Herb Society; The Register of Chinese Herbal Medicine (RCHM); The College of Practitioners of Phytomedicine; The Herb Society of America (HAS); Ayurvedic Practitioners Association (APA); National Institute of Medical Herbalists (NIMH); The National Herbalists Association of Australia (NHAA); American Herbalists Guild; American Ayurvedic Association; National Ayurvedic Medical Association; Ontario Herbalists Association; New Zealand Association of Medical Herbalists (NZAMH); Society for Phytotherapy; British Herbal Medicine Association (BHMA).

We included only RCTs of individualised herbal medicine with prescriptions individually tailored for each patient in any indication. Studies combining individualised herbal medicine with other treatments were excluded unless the design allowed the separate evaluation of the effectiveness of the herbal medicine component.

Results

The literature search identified 1345 references and 15 potentially relevant references, for which full text articles were obtained. Only three trials¹–3 met the inclusion criteria (Table 1). All three are randomised, double-blind, placebo-controlled RCTs of moderate to good methodological quality with Jadad scores of 5¹, 3² and 5³.

Bensoussan et al.¹ compared individualised Chinese herbal medicine, standardised Chinese herbal medicine and placebo in 116 patients with irritable bowel syndrome (IBS). Treatment lasted 16 weeks and in the individualised group, the prescription could be adjusted by the herbalist at regular intervals. Herbs were administered as encapsulated powders and the standardised treatment was a combination of 20 different herbs. Outcome measures were change in total Bowel Symptom Scale (BSS) and global improvement, each assessed separately by the patient and a gastroenterologist, and patient-assessed interference with life. The findings presented in the abstract and results sections of this paper differ. The abstract reports statistically significant findings favouring herbal treatment over placebo but this refers to data derived from standardised and individualised herbal treatment combined. The results section indicates that there were statistically significant differences favouring standardised treatment over placebo in all five outcome measures, but only four of the five showed significant intergroup differences favouring individualised herbal treatment over placebo. The gastro-enterologist’s assessments for the main outcome measure, the BSS, were not significantly better than placebo in the individualised group. Overall, changes from baseline and responder rates were larger in the standardised than in the individualised group in all measures. Patient-assessed BSS at a follow-up 14 weeks after the end of the trial favoured individualised over standardised treatment but this difference was not statistically significant.

The data for Hamblin et al.² were extracted from a pre-publication draft kindly made available to us by the authors. This study compared 10 weeks of individualised herbal medicine with a placebo tincture in 20 patients diagnosed with osteoarthritis of the knee. The herbal treatments were prescribed by two herbal practitioners, each based at a different London GP surgery. Prescriptions drew upon a formulary of 11 herbs based upon responses to a questionnaire completed by 20 established herbalists. Patients continued with existing pain-killing and anti-inflammatory drugs for the period of the trial and, in addition to the active or placebo treatments, received dietary advice and daily nutritional supplements consisting of multivitamins and minerals, vitamin C and omega-3 fish oils. Outcome measures were subscale scores and total score for the WOMAC and Measure Yourself Outcome Profile (MYMOP) scores for two symptoms and a daily activity chosen by each patient. Fourteen of the 20 patients enrolled in the study completed the 10-week trial and data analysis is based on these completers. There were no significant differences between groups in changes from baseline for either outcome or their component scores. The authors do report several within-group changes confined to the active treatment group, but the only one of these within-group changes to reach statistical significance were the WOMAC stiffness score at 5 weeks and symptom 2 on the MYMOP at both time intervals.

Mok et al.³ compared the effect of individualised Chinese herbal medicine with that of placebo upon chemotherapy-induced toxicity in patients with early-stage breast and colon cancer. Individualised treatment was prescribed by one of three qualified Chinese herbalists drawing on a stock of 125 different commonly used herbs. Treatments, including the placebo, were dispensed in the form of a herbal tea. Treatment could be adjusted by the herbalist on day 1 and 14 of each cycle of chemotherapy. Chemotherapy was standardised as four 21-day cycles for breast cancer and six 28-day cycles for colon cancer. The trial was terminated early, when 50% of the target sample size had been recruited, because of a slow accrual rate. Many potential recruits refused the possibility of being randomised to placebo or were already receiving Chinese herbal medicine. Data analysis for 111 patients showed no statistically significant differences between groups for the primary outcome measure of haematological toxicity. There were no significant differences between groups for responses to a quality of life questionnaire and only one of 16 items measuring non-haematological toxicity showed a significant difference favouring the active treatment. This one difference related to nausea but a similar difference between groups was not observed in the item relating to nausea in the quality of life questionnaire.

Discussion

Systematic searches of electronic databases and contacting experts and professional bodies in the field resulted in the location of only three RCTs of individualised herbal medicine. It should be stressed that 15 professional bodies representing the interests of different practitioner bodies from around the world were unable to contribute any further studies. In view of the long history and widespread use of medical herbalism, Chinese herbal medicine and Ayurvedic herbal medicine in many and diverse indications, this should be a cause for concern. It indicates that individualised herbal medicine has an extremely sparse evidence base and

See Table 1: Included RCTs of individualised herbal medicine.

AC = adriamyacin and cyclophoshamide; BSS, Bowel Symptom Scale; CHM, Chinese herbal medicine; EORTC QoL, European Organisation for Research and Treatment of Cancer Quality of Life questionnaire version 2; FUFA = 5-fluorouracil and folinic acid; IBS, irritable bowel syndrome; MYMOP, Measure Yourself Outcome Profile; NSD, non-significant difference; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

that there is no convincing evidence supporting its use in any indication. Only one of the three studies¹ indicated that individualised treatment was superior to placebo and this study is particularly important because it found that individualised treatment was inferior to standardised treatment. This study sets a new benchmark for the tailored approach: not only must herbalists demonstrate that individualised treatment is superior to placebo, they must also show, for reasons of cost and safety, that it is superior to standardised treatment. Claims by herbalists who use the individualised approach that their practice is evidence based are disingenuous because evidence supporting the use of herbs for any indication has come almost entirely from the study of single, standardised herbal extracts – not from studies of individualised herbal medicine using combinations of several or many different herbs prepared from inherently variable raw plant materials. The paucity of data supporting the effectiveness of individualised herbal medicine and the important safety concerns associated with this particular form of phytomedicine should be taken into account by policy-makers concerned with the regulation of practitioners using this modality.

Overall, the results of the three studies included in this review do not provide support for the use of individualised herbal medicine in any indication. Despite optimistic reporting of positive trends in the Hamblin² study, there were no statistically significant differences favouring active over placebo treatment in osteoarthritis of the knee and the trends observed are probably the result of large baseline differences and regression to the mean. While Bensoussan¹ observed that individualised treatment was better than placebo in four of five outcome measures in the treatment of IBS, it was inferior to standardised treatment in all five outcomes and standardised treatment therefore appears to be preferable for reasons of cost and safety. Finally, the Mok study³ failed to provide evidence that individualised herbal treatment is superior to placebo in the prevention of chemotherapy-induced toxicity. These data indicate that almost all individualised herbal medicine is practised without the support of any rigorous evidence about effectiveness whatsoever.

All three trials do demonstrate that rigorous RCTs of individualised herbal medicine are entirely feasible. There is, however, a problem with the generalisability of results from such studies because of the non-standardised nature of the treatment. The large number of single herbs from which individualised treatments are prepared, differences between herbalists in prescribing practice and the lack of information about the actual treatments prescribed all mean that replication of findings is difficult. Even if precise prescribing information was reported for each patient, it is difficult to envisage how these data could be productively used when comparing different studies, other than for generating hypotheses about particularly effective component herbs. The lack of standardisation and use of multiple herbs in a single prescription also greatly multiply the safety risks and there are additional risks associated with variability in the diagnostic skills of the practitioner, their awareness or lack of awareness of potential interactions and their ability or inability to identify red flag symptoms indicating serious diseases requiring immediate mainstream medical treatment. Given the risks and lack of supporting evidence, the use of individualised herbal medicine cannot be recommended in any indication.

Conclusion

Individualised herbal medicine as practised in Euro-pean medical herbalism, Chinese herbal medicine and Ayurvedic herbal medicine has a very sparse evidence base and there is no convincing evidence that it is effective in any indication. Because of the high potential for adverse events and negative herb–herb and herb–drug interactions, this lack of evidence for effectiveness means that its use cannot be recommended.

References

1. Bensoussan A, Talley NJ, Hing M et al. Treatment of irritable bowel syndrome with Chinese herbal medicine. JAMA 1998; 280: 1585–89. [Abstract]
2. Hamblin L, Laird A, Walker AF. Reduced osteoarthritis symptoms from practitioner-prescribed herbal treatment: a randomised, double-blind feasibility study (pre-publication draft of a study under review, 2007.
3. Mok TSK, Yeo W, Johnson PJ et al. A double-blind placebo-controlled randomized study of Chinese herbal medicine as complementary therapy for reduction of chemotherapy-induced toxicity. Ann Oncol 2007; 18: 768–74. [Abstract]