Herbalsim in the face of the EBM Challenge

[Guest guest]

Hi All,

 

On 14 Jan 2003 Julie Chambers <info

wrote:

 

> Does anyone know of a good research study on any female disorder

> (sexual dysfunction, menopausal syndrome, PMS, etc) treated with

> any Chinese formula (not single herbs)? I am trying to help a

> colleague who is preparing a presentation for OB/GYNs on Chinese

> medicine. I have been to MedlinePlus and Blue Poppy websites and

> cannot find anything suitable. Thank you. Julie

 

My first reaction was that Julie must not know how to search

Medline because I expected that there would be hundreds of

relevant hits in that area. After all, females are 50% of the world’s

population and gyn/obs problems are a significant part of medical

practice.

 

Therefore I decided to search Medline for the following profile:

(herbal* OR phyto* OR kampo OR chm OR chinese-medicine* OR

japanese-medicine*) AND (prescription* OR formula* OR remedy

OR drug*) AND (controlled-trial*) AND (treatment OR therapy OR

prevent*) AND (sexual-dysfunction* OR sexual-disorder* OR infertil*

OR genital* OR uter* OR ovar* OR metrorr* OR metrit* OR partur*

OR miscarr* OR abort* OR dysmenorr* OR amenorr* OR pre-

menstrual-tension OR pmt OR pms OR menopaus* OR gyn* OR

obstetr*).

 

To my horror, I discovered that Julie was correct (sorry for doubting

you Julie!); I could find only TWO hits of any possible relevance to

Julie’s project:

 

#1 (Seidl et al, 1998) concluded: “In available controlled studies,

the strongest data support phytoestrogens for their role in

diminishing menopausal symptoms related to estrogen deficiency

and for possible protective effects on bones and the cardiovascular

system. RCTs, standardization of dosage, and accurate safety and

efficacy labeling are required to ensure proper use of alternative

remedies”.

 

#2 (Davies et al, 2001) concluded: “The defined formula of CHM

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.”

 

There were a few more hits, but NONE was relevant; they related

mainly to organic compounds used in cancer chemotherapy. All

the gyn/obs hits that I could find are at the end of this mail.

 

I then decided to widen the search to see what evidence, based on

controlled trials, there is for herbalism as a whole. I searched for

the profile: (herbal* OR phyto* OR Kampo OR CHM OR Chinese-

medicine* OR Japanese-medicine*) AND (prescription* OR

formula* OR remedy OR remedies OR drug*) AND (controlled-trial*

OR “controlled trial” OR “controlled trials”).

 

I was stunned by the (lack of) results!! I could find only 20 valid hits

for controlled trials of herbal formulas (2 inconclusive, 3 with no

benefit and 15 positive) and 61 valid hits for controlled trials of

single herbs or extracts (17 inconclusive, 9 with no benefit and 35

positive). In particular, as one who takes (and has first hand

experience of the effects of) the King of all herbs - Korean Red

Ginseng) - I was stunned by the absence of good data on ginseng.

Of only 3 references, 1 was positive towards American Ginseng but

2 found no significant benefit.

 

Below is a summary of a paper that I am starting to draft on the

topic. I invite (will welcome) your comments/criticism on this (draft)

summary.

 

I also I invite you to adapt my search profile [3 paragraphs up] and

do your own trawl of Medline. Can YOU find many more controlled

trials of ANY herbs OR formulas than I have on Medline?

 

If you are as unsuccessful as I, then dear colleagues, we are in

deep S**T if we ever need to justify our use of herbals by the

standards of EBM!

 

[see Sako et al. [Practice guidelines in western countries - Article

in Japanese] Gan To Kagaku Ryoho 1999 Apr;26 (5):602-8:

“Practice guidelines are not actually adopted in European

countries. However, the concept of guidelines is well appreciated &

medical practice is based on scientific evidence. In socialistic

European countries like Sweden, Denmark or the Netherlands,

there is huge pressure to control limited social resources, leading

to aggressive efforts to reduce unexplained & inappropriate

variations in medical practice.”]

 

I do not want to seem paranoid, or to suggest a conspiracy

between Governments and the Pharmaceutical Industry, but could

it be just coincidence that two of the (few) herbs for which

controlled trials showed statistically significant effects (Kava and

Hypericum) have both been banned from OTC sale?

 

It has been a very disappointing day for me!

Best regards,

Phil

 

PS: One name keeps cropping up on Medline in relation to meta-

analysis of herbal medicine (and AP) – that of Dr. E. Ernst

<E.Ernst, Dept of Complementary Medicine, School of

Postgraduate Medicine & Health Studies, University of Exeter, UK.

I reckon that he is strict, sceptical but very fair. Would the

ListMaster consider inviting Dr. Ernst to join the List?

 

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Herbal Medicine in State-regulated Western Society: Quo Vadis?

 

 

(Draft) Summary: Medline is the main database on western

medical research and clinical medicine. It also indexes the main

western herbal and oriental medical journals, including Chinese,

Japanese and Korean journals. Medical journals not indexed by

Medline usually have little or no scientific value because of

unacceptably low editorial standards and/or because those journals

have an inadequate system of peer-review before publication.

 

On Jan 14th 2003 a Medline search was conducted for the profile

(herbal* OR phyto* OR Kampo OR CHM OR Chinese-medicine*

OR Japanese-medicine*) AND (prescription* OR formula* OR

remedy OR remedies OR drug*) AND (controlled-trial* OR

“controlled trial” OR “controlled trials”).

 

That search profile should return the vast majority of Medline hits

that relate to herbal medicine. However, from >12 million titles, it

returned only 181 hits (0.0015% of the Medline titles). Removal of

“controlled trial” qualifier produced 20844 hits, i.e. >99% of the so-

called “herbal hits” were uncontrolled trials.

 

Even the 181 “controlled herbal trial” hits is a gross overestimate,

as is the 20844 total “herbal hits”. This is because most herbal hits

related to organic chemicals (conventional hormones, steroids,

chemotherapeutic drugs like mitomycin C, etc) that do not qualify

as genuine herbal products in the usual definition of the term.

However the ratio of “controlled” to “uncontrolled” herbal trial hits

(0.87 per 100) is probably close to the mark.

 

Overall, only 61/161 “controlled trial hits” were controlled trials of

genuine herbs or herb extracts. Of those, 35 were positive (as good

as the positive control, or better than the placebo control), 9 were

negative (no different from the placebo control) and 17 were

inconclusive/undecipherable [not enough data or Abstract was non

specific]. As regards herbal formulas (as distinct from single

herbs), there were only 20 “controlled trial hits” (15 positive, 3

negative and 2 inconclusive).

 

By the conventional standards adopted in western medicine, that is

a DAMNING indictment of herbalism. Sceptics might conclude that

herbalists, especially those who use FORMULAS, are using

products for which there is no acceptable level of published

scientific proof of their clinical efficacy.

 

The trend for litigation in cases of negligence, incompetence, or

even of simple medical failure is increasing in the west. Therefore,

more and more National Medical Councils and their underwriting

Insurance companies require their members to use only those

therapeutic methods that satisfy the academic standards of

Evidence-Based Medicine (EBM).

 

Also, national registration of medicinal products demands very high

levels of proof of safety, efficacy and QC. Therefore, even if herbal

manufacturers can prove safety and QC, unless they can find major

investment within or outside their industry to fund adequate

research on clinical efficacy the future of herbal medicine in the

west is very bleak.

 

In spite of popular demand, and in spite of the clinical experiences

and personal convictions of thousands of qualified and highly

ethical western herbalists, herbal extracts and formulas will remain

unregistered as medicinal drugs; they will remain relegated to the

category of OTC food-supplements or health supplements of

dubious medicinal value. This is a great pity, but it is a fact of life in

highly regulated societies that demand “consumer protection”

under the umbrella of EBM.

 

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

 

APPENDIX:

 

Medline hits for Julie’s gyn/obs controlled-trial project, of which

only TWO had any relevance whatsoever:

 

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

 

1. Can Fam Physician 1998 Jun;44:1299-308 Erratum in: Can Fam

Physician 1998 Aug;44:1598 | Alternative treatments for

menopausal symptoms. Systematic review of scientific and lay

literature. | Seidl MM, Stewart DE. Toronto Hospital. | OBJECTIVE:

To review the scientific literature on common alternative remedies

for treatment of symptoms attributed to menopause and to contrast

this with available lay literature. QUALITY OF EVIDENCE:

Scientific articles were identified by searching MEDLINE, CINAHL,

and HEALTH databases from 1966 to mid-1997 for English-

language articles. More than 200 references were reviewed; 85

were selected for citation based on specific reference to alternative

medicine for symptoms commonly attributed to menopause (e.g.,

hot flashes), to the effects of changing estrogen levels (e.g.,

irregular menses, vaginal dryness), and to reported side effects of

the treatments. MAIN FINDINGS: The scientific literature was

categorized under the headings nutritional supplements, herbal

remedies, homeopathic remedies, and physical approaches. Some

scientific evidence of the safety and efficacy of alternative

treatments during menopause was uncovered, with the strongest

evidence emerging in favour of phytoestrogens, which occur in high

concentrations as isoflavones in soy products. CONCLUSIONS: In

available controlled studies, the strongest data support

phytoestrogens for their role in diminishing menopausal symptoms

related to estrogen deficiency and for possible protective effects on

bones and the cardiovascular system. RCTs, standardization of

dosage, and accurate safety and efficacy labeling are required to

ensure proper use of alternative remedies. Publication Types:

Review Review, Academic PMID: 9640524

 

2. Med J Aust 2001 Jan 15;174 (2):68-71 Comment in: Med J Aust.

2001 Aug 20;175 (4):230. Med J Aust. 2001 Jan 15;174 (2):63-4. |

The effects of CHMs on postmenopausal vasomotor symptoms of

Australian women. A RCT. | Davis SR, Briganti EM, Chen RQ,

Dalais FS, Bailey M, Burger HG. The Jean Hailes Foundation,

Melbourne, VIC. suedavis | OBJECTIVE: To

evaluate the effects of a defined formula of CHMs 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 CHM (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 CHM (-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 CHM 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 CHM 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. Publication Types: Clinical Trial RCT

PMID: 11245505

 

Gan To Kagaku Ryoho 1993 Dec;20 (16):2454-60 | [strategy for the

ovarian cancer treatment - Article in Japanese] | Ochiai K. Dept. of

Obstetrics and Gynecology, Jikei University School of Medicine. |

The morbidity and mortality rate of ovarian cancer patients are

significantly inclined recently in Japan. FIGO stage is a powerful

prognostic factor, hence treatment schedule must be based on

precise staging. For stage I patients, total abdominal hysterectomy

(TAH), bilateral salpingo-oophorectomy (BSO), partial

omentectomy (p-OMTX) and appendectomy (APX) are included to

standard surgical procedure. Adjuvant chemotherapy consisted

with CAP (cyclophosphamide, adriamycin, cisplatin) or CP is given

for 5 courses postoperatively. However, those who are stage Ia

(grade 1) and desire child bearing could have unilateral salpingo-

oophorectomy and conserve conceptability. Adjuvant

chemotherapy for those patients is now on prospective RCT in

Japan. One arm is 50 mg/day of cyclophosphamide for 3 months

and the other arm is cyclophosphamide 500 mg/m2 + CDDP 75

mg/m2 every 4 weeks for 3 courses. For stage II or more patients,

total omentectomy and retroperitoneal lymphadenectomy are

added to above mentioned procedure. Cisplatin (15.75 mg/m2/week

or more) based adjuvant chemotherapy is given for 5-10 courses.

Therapeutic significance of retroperitoneal lymphadenectomy is

also under study in patients who are optimally debulked (< 2 cm

residual tumor). They are randomly divided into two groups:

lymphadenectomy group and no-lymphadenectomy group. They

receive 5 courses of CP therapy (cyclophosphamide 600 mg/m2 +

CDDP 75 mg/m2) afterwards. Survival rate and time to progression

are the primary endpoints. Publication Types: Clinical Trial RCT

Review Review Literature PMID: 8279841

 

Gan To Kagaku Ryoho 1995 Feb;22 (3):357-64 | [Cervical cancer--

phase III studies of radiation therapy combined modality - Article in

Japanese] | Ochiai K. Dept. of Obstetrics and Gynecology, Jikei

University School of Medicine. | The number of patients with

cervical cancer has been constantly reduced but it remains a

leading cause of death among gynecologic malignancies in Japan.

In 1990, 5,793 patients with cervical cancer were registered and

1,892 cases (32.7%) were stage 0, 2,074 cases (35.8%) were

stage I, 991 cases (17.1%) were stage II, 659 cases (11.4%) were

stage III and 172 cases (3.0%) were stage IV. Among these

patients, about 40% were treated with radiation therapy alone or

combined with radiation therapy. The five-year survival rates of

stage I, II, III, and IV patients were 83.4%, 65.3%, 40.3% and

13.1%, respectively. Phase III studies have been conducted to

compare surgical treatment and radiation therapy, and it is clarified

that radiation therapy is equivalent to surgical therapy in young

healthy patients with an early-stage tumor, while combined

radiation therapy followed by surgery did not improve results over

radiation alone. It is thus justified to offer postoperative irradiation to

selected patients who have high-risk factors in the surgical

specimen. Effects of chemotherapy were also compared to

radiation therapy. Multiagent chemotherapy such as bleomycin,

vincristine, MMC, and cisplatin or bleomycin, ifosphamide and

cisplatin are standard regimens for cervical cancer. However,

because the toxicity of chemotherapy along with radiation therapy

is much higher than that of radiation alone, there is a need to

develop an adequate adjuvant chemotherapy regimen for cervical

cancer. Other ongoing trials are also discussed. Publication Types:

Review Review, Tutorial PMID: 7880106

 

Gan To Kagaku Ryoho 1997 Oct;24 Suppl 3:418-25 | [state of the

art: treatment of malignant pleural and pericardial effusions - Article

in Japanese] | Saka H, Shimokata K. First Dept. of Internal

Medicine, Nagoya University School of Medicine. | Symptomatic

malignant pleural effusions should be treated systemic

chemotherapy in chemo-sensitive tumors such as small cell lung

cancer, breast cancer, lymphoma, or ovarian cancer. In other non-

chemo-sensitive malignancies including non-small cell lung cancer,

water-sealed tube drainage and pleurodesis is the standard

treatment of choice in most of the cases. Drugs for instillation

should be blomycin or OK-432 if commercially available. Instead of

the former standard drug tetracycline, doxycycline has been

frequently used. As we have no RCTs, this drug awaits phase III

trials. Talc slurry has been accepted and counted as one of the

standard choices in the western countries, however, it usually

needs general anesthesia and adverse effects are not negligible.

As we have little experience on this modality, it should not be

considered as a standard treatment. Other antitumor drugs

instillation, thoraco-abdominal shunting, and pleuro-

pneumonectomy should be considered experimental because of

the lack of RCTs. Symptomatic pericardial malignant effusion or

cardiac tamponade is an oncologic emergency. We had better to

treat the patient immediately by pericardiocentesis under the

cardiac echographic guidance. It should be reserved to solve in

RCTs that the best method would be pericardiocentesis alone,

percutaneous continuous drainage, pericardial fenestration, or

pericardio-thoraco fenestration. Instillation of drug like doxycycline,

OK-432, or bleomycin, lacks phase III comparison and it should be

categorized as experimental. Publication Types: Review Review,

Tutorial PMID: 9369917

 

Gan To Kagaku Ryoho 2001 Jul;28 (7):934-45 | [Hormonal therapy

for endometrial adenocarcinoma - Article in Japanese] | Susumu N,

Aoki D, Suzuki N, Nozawa S. Dept. of Obstetrics and Gynecology,

School of Medicine, Keio University. | Recently, the number of

cases of endometrial cancer has increased in Japan. Most of the

increase are accounted for by premenopausal cases, which are

frequently positive for ER or PR. Hormonal treatment using

progestins such as MPA has been widely applied to endometrial

cancer patients under 40 years old under the conditions of grade 1

well-differentiated endometrioid adenocarcinoma without

myometrial invasion. In our hospital, we applied high-dose (600

mg/day) MPA for over 8 weeks in 14 cases of endometrial cancer,

of which adenocarcinoma disappeared in 12 cases (86%), followed

by cyclic administrations of low-dose MPA, with 7 subsequent

recurrences. We think that a protocol for improving ovarian function,

such as active induction of ovulation, should be established to

induce intrinsic progesterone sufficient for the prevention of the

recurrence of endometrial cancers. In the 2 cases, in which

adenocarcinoma remained even after long administrations of MPA,

myometrial invasion was noted in the surgically resected

specimens. For advanced or recurrent endometrial cancers, MPA

has been reported to be effective in an average of 26% in several

reports, and effective in 42% cases when applied with combination

chemotherapy, such as CAP, by virtue of the " chemical modulator "

effect, which can delay the acquired resistance against ADM or

CDDP. Furthermore, MPA has resulted in a significant

improvement of 5-year disease-free survival rate when used as

adjuvant therapy after complete operations and whole pelvic

irradiation, compared with administrations of 5-FU in a randomized

controlled study in Japan. Thus, in the future, we consider that

hormonal therapy will play a more important role in endometrial

cancer treatment. Publication Types: Review Review, Tutorial

PMID: 11478142

 

Gan To Kagaku Ryoho 2002 Aug;29 (8):1351-7 | [Latest information

in the diagnoses of ovarian carcinoma - Article in Japanese] |

Isonishi S. Dept. of Obstetrics and Gynecology, Jikei University

School of Medicine. | Despite improvements in median and overall

survival from a combination of improved operation techniques and

chemotherapy with platinum-compounds and paclitaxel, long-term

survival rates for patients with epithelial ovarian carcinoma remain

disappointing, and ongoing efforts are aimed at developing more

effective primary therapies. In early ovarian carcinoma, conservative

management is used to denote surgery that preserves reproductive

potential without compromising curability. With some exceptions,

such a strategy may be applicable for women younger than 40,

who wish to bear children. A major dilemma facing gynecologic

oncologists is to determine whether the accurate staging

laparotomy is needed for apparent low-risk stage I ovarian

carcinoma and how many cycles of chemotherapy will be needed

for high-risk stage I ovarian carcinoma. In advanced ovarian

carcinoma, main objectives of salvage therapy include: a

improvement in quality of life and symptoms; b. tumor load

reduction and survival advantage; c. evaluation of potentially active

new drugs to be included in first-line treatment. We need to

evaluate the potential benefit on survival of systematic pelvic and

para-aortic lymphadenectomy during primary or secondary

cytoreductive surgery in patients with advanced ovarian carcinoma.

Paclitaxel/cisplatin is considered to be the international standard

treatment based on the data of GOG 111 trial showing that

paclitaxel/cisplatin has provided a survival benefit better than that of

cyclophosphamide/cisplatin. This choice of standard therapy

might, however, be questioned based on the results of the largest

randomised study, ICON3. There were no statistically significant

differences in progression-free or overall survival among

paclitaxel/carboplatin and carboplatin only or a platinum

combination (cyclophosphamide/doxorubicin/cisplatin). The best

selection for adjuvant chemotherapy is still controversial and a

large number of studies are now ongoing. Publication Types:

Review Review, Tutorial PMID: 12214460

 

Nippon Rinsho 2002 Mar;60 Suppl 3:552-71 | [Drugs in

development for the treatment of osteoporosis: Tibolone - Article in

Japanese] | Gorai I. Department of Obstetrics and Gynecology,

Yokohama City University School of Medicine. | No Abstract

available. Publication Types: Review Review, Tutorial PMID:

11979954

 

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Best regards,

 

 

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[Guest guest]

Wow, Phil. Thank you for doing all that. You certainly are more proficient

at searching Medline than I am.

 

Julie Chambers

 

Phil had written:

 

Therefore I decided to search Medline for the following profile:

(herbal* OR phyto* OR kampo OR chm OR chinese-medicine* OR

japanese-medicine*) AND (prescription* OR formula* OR remedy

OR drug*) AND (controlled-trial*) AND (treatment OR therapy OR

prevent*) AND (sexual-dysfunction* OR sexual-disorder* OR infertil*

OR genital* OR uter* OR ovar* OR metrorr* OR metrit* OR partur*

OR miscarr* OR abort* OR dysmenorr* OR amenorr* OR pre-

menstrual-tension OR pmt OR pms OR menopaus* OR gyn* OR

obstetr*).

 

To my horror, I discovered that Julie was correct (sorry for doubting

you Julie!); I could find only TWO hits of any possible relevance to

Julie's project: