Clinical trials, clinically tested, clinically proven. You see these terms used with lots of products (including ours), but what does it actually mean?
Clinical Trials – Huh?
We often hear medical professionals advising us not to take supplements that do not have evidence of efficacy (effectiveness). Usually, they describe this in words such as “clinically proven”, or “having undergone clinical trials”.
The reason is that medical practitioners are concerned about the health, safety and welfare of their patients. They see too many examples of patients taking medicines and supplements that at best will have no tangible benefit. At worst they could actually be harmful.
I totally endorse this considered professional approach to prescribing medicine and supplements
Evaluating 40+ & 55+
I’ve worked in the pharmaceutical industry developing prescription medicines for over 30 years. I fully understand the need for rigorous testing and trialing of products for both safety and efficacy.
This is why I fully evaluated all the available clinical data on EstroG-100™ (the active ingredient in 40+ & 55+). It was only then that I decided to bring this amazing product to New Zealand and Australia.
Let me describe what the term “clinically proven” means and what happens when a product undergoes clinical trials.
There are five phases in a clinical study:
- Phase 0: Exploratory study involving very limited human exposure to the drug, looking at micro-dose effects, screening studies, and with no efficacy or diagnostic outcomes evaluated.
- Phase 1: Studies that are usually conducted with healthy volunteers and that emphasize safety. The goal is to find out what the drug’s most frequent and serious adverse events are and, often, how the drug is metabolised and excreted.
- Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition). For example, participants receiving the drug may be compared to similar participants receiving a different treatment, usually, an inactive substance called a placebo or a different drug. Safety continues to be evaluated, and short-term adverse events are studied.
- Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
- Phase 4: Studies occurring after the regulator (Ministry of Health in New Zealand, or FDA in the USA) has approved a drug for marketing. These include post-market requirements and commitment studies that the regulator required as a condition of approval. These studies gather additional information about a drug’s safety, efficacy, or optimal use.
In the case of EstroG-100™, which has undergone clinical trials even though it is not a drug, safety was already well established prior to it being used for alleviating the symptoms of menopause. This is because the herbal ingredients in 40+ & 55+ (EstroG-100™) have a long history of safe use as culinary herbs in Asia. So much of the work in phase 0, 1 and 2 was not required.
The following outlines the type of clinical trial that was conducted on EstroG-100™.
Double Blind Placebo
The gold standard for clinical trials is the double-blind placebo-controlled clinical trial.
In these trials, half of the patients receive the drug and half receive a placebo. This is a product that looks exactly like the real thing but has no active ingredient in it.
The purpose of this is to rule out any psychological effect. You only have to experience the magical power of a child’s misery instantly fixed by a teaspoon of medicine, or the child’s “broken leg” fixed by a sticking plaster to understand that the placebo effect is very strong.
It is estimated that for certain drugs a sugar tablet placebo can have a placebo effect of up to 40 per cent. Therefore, to measure the true effectiveness of a drug you need to measure this effect and see how much better than the placebo the real drug effect is.
The “double blind” part of the gold standard clinical trial means that neither the patient nor the investigator administering the drug knows who gets the active and who gets the placebo.
All samples are coded and the code is only revealed after the trial is complete and the data is all collected. This rules out any possibility of bias in the data that is generated.
Statistical analysis plays a big part in clinical trials. The trial has to be large enough, have enough patients so that the results can be validated as statistically significant.
The term “confidence level” is used to describe the probability of an outcome. This results in a P value, such as P<0.01, which means the probability is less than 0.01 (1%) that the effect observed is due to chance. In other words, we are 99 per cent certain that this is a true effect of the product.
This is often a tough test, especially for natural products and supplements which often have more variable results than standard pharmaceuticals.
Natural products vary in their natural composition depending on factors such as the season the herb was harvested, the weather and soil conditions, the way the herb is harvested and processed. So you can expect to see much better results in some patients than other patients. And with variability, you need to have even higher statistical power to be able to prove that the product is efficacious to the general population, not just the lucky few.
So I was astounded when I reviewed the clinical trial data for EstroG-100™ (which is a herbal natural product for menopause and the active ingredient in of 40+ & 55+). The proof of efficacy was exceptional, and the widespread nature of the relief of menopausal symptoms was amazing.
Below is the abstract (summary) of the publication on the study conducted in the USA in 2011 and published in PHYTOTHERAPY RESEARCH in 2012. Phytother. Res. 26: 510–516 (2012)
This clinical research study was designed to evaluate the efficacy of a new herbal product, EstroG-100™, containing a mixture of standardized extracts of Cynanchum wilfordii, Phlomis umbrosa and Angelica gigas, on menopausal symptoms. This randomized double-blind, placebo-controlled trial was performed for 12 weeks with 64 pre-, peri- and postmenopausal White Hispanic, White non-Hispanic and African American women who were randomly allocated to either the EstroG-100™ group (n = 31) or the placebo group (n = 33). Primary end-points were the mean change in scores of the Kupperman menopause index (KMI) that evaluates 11 symptoms, and the mean change in scores of vaginal dryness. The mean KMI score was significantly reduced in the EstroG-100™ group from 29.5`7.4 at baseline to 11.3`5.8 (p<0.01) compared with change of the placebo group (29.2 ` 6.6 at baseline vs 23.7 ` 7.7 at week 12). The constituting symptoms of vasomotor, paresthesia, insomnia, nervousness, melancholia, vertigo, fatigue and rheumatic pain were significantly improved in the EstroG-100™ group in comparison with the placebo group (p < 0.05). Statistically significant improvement in vaginal dryness in the EstroG-100™ group was also observed compared with that of the placebo group (p < 0.05). In conclusion, EstroG-100™ significantly improved the menopausal symptoms of pre-, peri- and post-menopausal women without weight gain or any serious side effects.
While there are 34 documented symptoms of menopause, only 12 of them are recognised as symptoms eligible for inclusion in clinical trials. These 12 symptoms make up the Quality of Life indicator measurement called the Kupperman’s index.
In short, EstroG-100™ was proven in this trial to alleviate 10 of the 12 symptoms of menopause, and the other two symptoms still showed improvement but it would need a larger and longer trial to prove statistical significance.
This was by far the best natural menopause product on the market, and the safety profile was so good that Health Canada allowed it to be marketed without any warnings on the label, the only clinically proven menopause product to have such a wide safety margin.
In addition, the safety and efficacy profile was so good that EstroG-100™ was not required to undergo phase 3 and 4 studies prior to market authorisation.
This was exceptional! So I just had to obtain the rights to bring EstroG-100™ to New Zealand and Australian women.
And thus began the start of our mission to share this product and knowledge as widely as we can in the hope that we can make life more comfortable and enjoyable for many women going through this life phase.
Article written by Peter Lehrke, BSc (Hons) Biochemistry; Dip.Nut.Sci. Technical Director MenoMe®. Over 30 years experience in pharmaceutical research, product development, manufacturing, project management and general management of dietary supplements, cosmetics, and nutritional products. Peter was part of the team at GMP Pharmaceuticals which won the Natural Products New Zealand industry Exporter of the Year Award 2007. He was responsible for the design and development of Douglas Pharmaceuticals Fiji facility, the first certified pharmaceutical factory in the Pacific Islands. Peter has also held roles with Glaxo Pharmaceuticals (now GSK), PharmaPacific (division of Fernz Corporation and Nufarm) and and New Image Group. Peter is currently serving on the Natural Health Products of New Zealand (NHPNZ) Board since 2009.