Sunday, April 04, 2010
BUSINESS CASE STUDY
The Situation
A new dietary supplement designed to facilitate joint health through a type of gene therapy was developed by specialist Life Sciences Company based in North America . Its market positioning was to provide an alternative to Glucosamine, one of the most widely used products for joint health. Thus, while there was a significant array of competitive products built around the glucosamine technology these products lack the ability to differentiate and suffer from a slow onset of action, moderate efficacy and an inability to maintain a sustained benefit.
A market research revealed that while the development of this product was supported by a Research Award from a Federal agency known for conducting and supporting medical research which is unique in this market niche, clinical support would be vital for market penetration.
The company had conducted a series of efficacy studies in animals and ex vivo studies in human cartilage explants to prove the pathways through which it acted (Mechanism of Action studies). Additionally, one botanical component of the product had already completed a pilot clinical trial in osteoarthritis patients but support for itself was needed.
Research concluded that the product acted by several yet complementary mechanisms at the genetic level, blocking inflammation while promoting repair. While these preclinical studies were state-of-the-art the current regulatory climate in the USA, specifically the US Federal Trade Commission (FTC), required a supportive double blinded randomized controlled study in order to make any references to clinical states in promotional material. In other words, marketing and promotional activity would be hampered without a clinical trial that was supportive of efficacy and safety. Additionally, entry into other markets had a mandate on supportive clinical research in order to commercialize the product in that country.
The Direction
A market research revealed that while the development of this product was supported by a Research Award from a Federal agency known for conducting and supporting medical research which is unique in this market niche, clinical support would be vital for market penetration.
The company had conducted a series of efficacy studies in animals and ex vivo studies in human cartilage explants to prove the pathways through which it acted (Mechanism of Action studies). Additionally, one botanical component of the product had already completed a pilot clinical trial in osteoarthritis patients but support for itself was needed.
Research concluded that the product acted by several yet complementary mechanisms at the genetic level, blocking inflammation while promoting repair. While these preclinical studies were state-of-the-art the current regulatory climate in the USA, specifically the US Federal Trade Commission (FTC), required a supportive double blinded randomized controlled study in order to make any references to clinical states in promotional material. In other words, marketing and promotional activity would be hampered without a clinical trial that was supportive of efficacy and safety. Additionally, entry into other markets had a mandate on supportive clinical research in order to commercialize the product in that country.
The Direction
A decision was made to investigate the possibility of conducting proprietary research to test the product clinically. The parent company did not have the resources to conduct and complete such a scientific study, so they decided to approach an appropriate medical school in the US that had substantial experience with dietary supplements research.
Despite conducting preclinical research within US Medical schools the execution of a clinical study at US medical schools was prohibitively expensive. It was confirmed that FDA and FTC did not have any specific guideline or restrictions for clinical data from outside of the US on a non-white population. In fact, a large number of drug trials submitted to FDA for approval are conducted outside the US of which a large portion is on a non-Caucasian patient population.
The trial design would be a double blind active controlled study, specifically glucosamine the market leader. The budgets were tight but quality could not be compromised because it was critical to take the results into a scientific peer reviewed publication. The only requirement for acceptance of foreign data in the US was that it should be conducted as per ICH GCP and monitored by an agency independent of the clinical investigators and the sponsor company. Hence it was decided that the study would be conducted inIndia with a suitable CRO who will comply with these guidelines and may be even at probably half of the costs in the US
Vedic Lifesciences, a CRO specializing in Pharmaceutical, Nutraceutical, and Cosmeceuticals research was identified as the right partner. Moreover, this CRO provided turnkey solutions which would make the trial much easier. They had US representation, were easy to communicate with and understood US conditions and regulations. They handled all aspects including:
Despite conducting preclinical research within US Medical schools the execution of a clinical study at US medical schools was prohibitively expensive. It was confirmed that FDA and FTC did not have any specific guideline or restrictions for clinical data from outside of the US on a non-white population. In fact, a large number of drug trials submitted to FDA for approval are conducted outside the US of which a large portion is on a non-Caucasian patient population.
The trial design would be a double blind active controlled study, specifically glucosamine the market leader. The budgets were tight but quality could not be compromised because it was critical to take the results into a scientific peer reviewed publication. The only requirement for acceptance of foreign data in the US was that it should be conducted as per ICH GCP and monitored by an agency independent of the clinical investigators and the sponsor company. Hence it was decided that the study would be conducted in
Vedic Lifesciences, a CRO specializing in Pharmaceutical, Nutraceutical, and Cosmeceuticals research was identified as the right partner. Moreover, this CRO provided turnkey solutions which would make the trial much easier. They had US representation, were easy to communicate with and understood US conditions and regulations. They handled all aspects including:
¨ Protocol writing
¨ Site Selection, qualification & management
¨ Ethical Approvals
¨ Central Laboratory Selection & Management
¨ Trial Supply Management
¨ Monitor & audit sites for protocol adherence
¨ GCP compliance Data Management
¨ Statistical Analysis
¨ Clinical Report Writing
Results
Results of the clinical trial can be downloaded from the Open Access scientific journal BMC Complementary Medicine at the following link www.biomedcentral.com
The product provided relief of arthritis symptoms within the first week of administration, in a manner that was generally superior to glucosamine.
Response rate to treatment based on a reduction in joint pain was an impressive 94% after 8 weeks of treatment. Response rates based on a variety of criteria were significantly greater for the product than glucosamine. Use of NSAIDs as a rescue medication was significantly less in the subjects treated by the product versus glucosamine treatment. The safety profile and physician and subject acceptance was excellent and supported its wide use in human populations.
Marketing
Response rate to treatment based on a reduction in joint pain was an impressive 94% after 8 weeks of treatment. Response rates based on a variety of criteria were significantly greater for the product than glucosamine. Use of NSAIDs as a rescue medication was significantly less in the subjects treated by the product versus glucosamine treatment. The safety profile and physician and subject acceptance was excellent and supported its wide use in human populations.
Marketing
The product was launched into the market via e-commerce. Sales were stimulated by TV interviews with Dr. Mark JS Miller, who was a critical member of the development team. A co-branding deal with one of America’s largest pharmacy chain was struck with their line of premium dietary supplements.
Critical factors in this sealing this marketing arrangement were the Research Award, the unique mechanism of action and the understanding that a clinical trial was commissioned and underway.
Promotional activities ranging from radio, advertorials, store coupons and In-store video presentations were held. Registration of the trial at www.controlled-trials.com and subsequent publication of the results in the peer reviewed journal BMC Complementary and Alternative Medicine, facilitated and augmented these promotional events. Indeed, if the clinical trial was not performed many of these activities would not have taken place and sales would have been compromised.
Critical factors in this sealing this marketing arrangement were the Research Award, the unique mechanism of action and the understanding that a clinical trial was commissioned and underway.
Promotional activities ranging from radio, advertorials, store coupons and In-store video presentations were held. Registration of the trial at www.controlled-trials.com and subsequent publication of the results in the peer reviewed journal BMC Complementary and Alternative Medicine, facilitated and augmented these promotional events. Indeed, if the clinical trial was not performed many of these activities would not have taken place and sales would have been compromised.
Business Analysis
First Year:
The product was introduced into a crowded market – dietary supplements for joint health – via e-commerce. The co-branding alliance was a major stimulus for sales and brand building. This arrangement would not have taken on the traction that it enjoys without the support of a solid clinical trial and its publication in a well respected peer reviewed journal and has become a major success.
Second Year:
Projections for Year 2 suggest that sales will continue to grow in a substantial manner with the projected analysis. New skus have been added and promotional activities will be maintained.
The product is likely to demonstrate success in other retail outlets as the distribution is expanded in the years to come. Nevertheless, the primary focus is to maintain the relationship with the companies for co-branding alliance.
Global expansion is under discussion for a number of countries.
The product is likely to demonstrate success in other retail outlets as the distribution is expanded in the years to come. Nevertheless, the primary focus is to maintain the relationship with the companies for co-branding alliance.
Global expansion is under discussion for a number of countries.
Continuing profits
This case study is an excellent example of how a crowded market like joint health can be approached with significant market penetration in a short period of time with superior product support, especially clinical trial evidence for safety and efficacy. Once market penetration has been established this foundation will continue to support market growth.
Summary
Clinical trial support allowed a new, innovative dietary supplement product to enter the crowded joint health market with substantial penetration. Sales were boosted with intelligent tie ups. Expansion of the markets within the USA and globally in subsequent years will foster continued growth.
Note: Dr. Mark Miller (PhD, MBA, FACN) currently serves as the Vice President of R&D at AdvoCare International (LP), Dallas/Fort Worth in
Monday, February 15, 2010
Selecting Health Claims for Nutraceutical Clinical Trials
(This article was published on Natural Product Insider magazine for December, 2009 Issue. http://www.naturalproductsinsider.com/articles/2009/12/selecting-health-claims-for-nutraceutical-clinical-trials.aspx )
Prior Data Available for Trial Design
Questions for a Proof of Concept Study
Consider the Variables
Jayesh Chaudhary is founder and CEO of Vedic Lifesciences, a CRO specializing in nutraceutical claim substantiation trials. He can be reached at jayesh.chaudhary@vediclifesciences.com or +91-98-210-86665.
Determining the primary question to be asked in a clinical trial of a dietary supplement is critical to its success. Ask a wrong question and you end up with the wrong answer, no answer or an answer that has no market or regulatory value. A complex human trial can be compared with a simpler scientific experiment consisting of a substrate (the patient or disease state), the reagent (the supplement or the intervention) and the endpoint (the outcome). Of course, clinical research has an added dimension of medical ethics that is absent from other research. In any study the scientist must smartly choose the correct substrate and watch for the mostly likely endpoint to prove a certain property of the reagent. In other words, selection of the wrong subject population and impractical clinical endpoints may result in failure of the clinical trial objectives.
How does one take these critical decisions regarding claim selection/definition and substantiation? First, look at what happens in conventional drug discovery and development, which provides lessons for planning effective clinical trials for dietary supplements. Next, consider all research decisions from the point of view of the investigator and, more importantly, the trial subject (the patient) in addition to the sponsor’s interests.
Prior Data Available for Trial Design
When a drug molecule enters Phase II clinical research, a trial phase that is comparable in its objective to typical nutraceutical trials, a lot is already known about the molecule from preclinical work. For most molecules entering Phase II, the target site of action, exact indication, disease sub-type, stage/severity of disease, probable safe and effective dose, expected duration of therapy, onset of action and half life of the drug in the body are known factors. The concept of the new drug already exists and needs to be proven in humans (Proof of Concept Study). The safety of the new chemical entity (NCE) in healthy humans in terms of maximum tolerable dose (MTD), likely adverse effects, etc., are also known through Phase I trials. The safety of the drug in patients is studied in further Phase II/III trials.
A systematic review of available data about folklore; identity, quality and strength of ingredients; and biological effects will help compile a respectable Investigators’ Brochure (IB) which will not only reassure IRBs, but also stimulate the imagination of investigators. They can suggest outcomes patients long for and value, which should therefore be measured or counted. For example, if a product facilitates epithelial healing (effect), and is shown to reduce the time required for re-epithelialization (efficacy), patients must find earlier or faster relief of symptoms (effectiveness).
For this discussion, let us consider only supplements that go beyond a nutritional benefit and are chosen to be studied for “hard” claims. While current regulations in most countries will allow only normal structure/function or quality-of-life type of claims, it is common practice to study the effect of nutraceuticals on a disease state. In the eyes of the regulators, even a “clinically proven” therapeutic product can not be labeled as a drug until it goes through the IND-NDA process consisting of several phases of human trials. Yet, it is often beneficial to have supplement studies done under an Investigational New Drug (IND) Application to FDA or local authorities to lend the study some credibility and improve quality of the research.
In comparison to NCEs, a typical herbal supplement that enters a human clinical study for the first time is not armed with much data. A lot can be dug out from folklore or traditional use of herbal remedies; but, a lot is often lost in translation from a traditional medical book to a modern clinical research protocol. Finding someone trained in both sciences—complementary and alternative medicine (CAM) and clinical pharmacology—can fill the void due to inadequate preclinical data. In the event that the supplement or ingredient is lacking in both ethnobotanical and in vitro/in vivo animal data, the task of choosing the correct label claim for the clinical trial becomes even more challenging. Such trials are just based on popular use without an established basis.
The Need for Exploratory Clinical Trials
In such situations, the first clinical trial of a lesser-studied nutraceutical becomes purely exploratory; not much is to be expected from such a trial in terms of marketable outcomes. While such studies may not yield marketable outcomes, their scientific value is immense in guiding further focused, well-powered studies. The primary question of such an exploratory study could read, for example: “Does a high dose of the Investigational Product (IP) reduce fasting blood glucose in type II diabetics?” The study will enroll a general diabetic population and follow up frequently to get an idea of onset of action and point when maximal response may be achieved. Since the dose is not known from earlier studies, subjects will be exposed to a relatively high dose in order to elicit some response, if it exists at all. The expected outcome from such a study is the birth of a “claim statement” or the hypothesis for the next study. This pilot study lays a strong foundation for the next confirmatory or proof-of-concept (PoC) study. In supplement parlance, the “claim definition” study paves the way for a “claim substantiation” study. This transforms a known or observed effect (feature) into a claim of efficacy (benefit). Later, a Large Simple Trial can establish the effectiveness (realizable benefit) of the product as it will be used when marketed.
Questions for a Proof of Concept Study
The primary question for the PoC could be something like: “Does x mgs daily of the IP reduce the fasting blood glucose levels of recently diagnosed non-obese type II diabetics to less than 120 mg/dl in two months?” This question assumes there will be no change in patient’s diet, exercise and diabetic medication during the course of the study. Further sub-questions could be: “Does this effect occur in patients with elevated blood lipids also?”, “Do diabetics on sulfonylureas benefit as much with this herbal supplementation as do diabetics on other medication?”, etc. It would be good to have indicative answers to those sub-questions from the exploratory pilot study. This is known as sub-group analysis.
Secondary questions could then be: “Does the IP lower elevated triglycerides and low-density lipoprotein (LDL) in the diabetic population also?” or “Does the IP reduce elevated nitrotyrosine in this population?” Glucose management along with reduction of nitrotyrosine, an important cardiovascular disease marker, would be the ultimate proof of the dual powers of a diabetes supplement that most drugs would shudder to even think about. A single well-designed study can help substantiate multiple related claims. Research sponsors must select a research partner (hospital or CRO) that is well-versed with dietary supplement regulations (FDA, FTC guidelines) as well as the supplement market, and also with the art of medical writing. At the moment, few companies are making claims based on onset of action and time for maximal response. Such statements could read: “fastest acting curcumin” or “clinically proven to improve quality of life significantly in less than one month as compared to two months…”
Consider the Variables
Clearly the choice of questions that can be asked in clinical research is unlimited, but not all from a single small study. Each question (intended claim) may warrant a different set of study population or lay specific restrictions on the type of recruits. Strong evidence requires statistical significance and, thus, a large enough sample of a homogeneous population. Each unrelated claim requires a specific population.
Claims involving objective research outcomes such as blood glucose and other quantifiable clinical or lab values are always more desirable for initial studies as compared with subjective efficacy variables, such as pain and feeling of well-being. Proving a hypothesis based on objective variables requires simpler designs (controlled studies are always better, but non-comparator studies are also possible) and smaller sample sizes. While some lab tests can be substantially more expensive than simple clinical questionnaires, it is always desirable to design claim statements bases on objective lab tests.
There will always be a tussle between advocates for soft claims (general benefit or improved well-being in patients with only mild disorders) and harder claims (significant improvement in quantifiable values of severe cases). While marketing and legal may decide on soft claims, the clinical research planner may still choose a harder claim to test in the research study. Depending on confidence levels from prior data, one may take on ambitious clinical endpoints or first prove the easiest marketable claim and then embark on more challenging studies.
Safety is a much-ignored variable and most dietary supplement companies fail to leverage the relative safety of their natural products to their advantage. Statements such as “clinically proven to help lose 2 pounds per month and three times safer than…” can add to a brand’s claims portfolio.
One of the stronger factors in deciding primary claims in clinical trials is available study budgets. It is unfortunate that financials often play a greater role in shaping trial design and sample size than is desirable. Cost constraints coupled with overambitious marketing goals often seal the fate of the study even before it starts. If it is difficult to conduct a confirmatory study on a sizeable sample within the limitations of time and budget in North America, then one should actively to consider offshoring it to Asia. Both India and China are already hot clinical trial destinations for big pharma as well as start-up biotechs. There is no reason why cost and quality-conscious nutraceutical firms should not look that way.
Investing in an experienced research partner (CRO) early in the program can help companies design good human studies. Conducting these studies in the most scientific manner required is another subject.
Jayesh Chaudhary is founder and CEO of Vedic Lifesciences, a CRO specializing in nutraceutical claim substantiation trials. He can be reached at jayesh.chaudhary@vediclifesciences.com or +91-98-210-86665.
Is My Product Ready for Clinical Trials?
(This article was published on Natural Product Insider magazine for November, 2009 Issue.http://www.naturalproductsinsider.com/articles/2009/11/is-my-product-ready-for-clinical-trials.aspx)
A clinical trial is considered low-hanging fruit in the dietary supplement industry, yielding immediate marketing value. Other types of data to support claims for a health ingredient or supplement are not as glamorous or accretive to the bottom line. Ideally, consumers want to know whether a product works on them and not just in animals. Regulators even specify controlled human studies are the gold standard for evidence of efficacy of health ingredients or drugs.
Before nutraceutical firms started to look at clinical trials in a big way, product marketers relied on testimonials from satisfied consumers and health care practitioners. Today, companies are increasingly dedicated to clinical trials; however, two types of preclinical research—“Formulation & Analytical Development” and “Animal Pharmacology & Toxicology”—are important, although the investment can seem costlier than the results.
Formulation & Analytical Development
As an example, suppose you have a novel compound from India that you want to market globally. Traditional knowledge and some in-house laboratory data substantiate certain health benefits. Ready to make that claim in most countries? Not without a passport.
The passport is a review of the finished product’s quality. Ingredient certificates of analysis (C of A) provide details on the ingredient itself; however, formulation and production steps ranging from granulation to tableting can impact the compound. Further, novel delivery systems and dosage forms also affect an ingredient’s bioavailability and stability.
On a global level, innovation in novel nutraceutical dosage forms has been slow, although some actives have been converted into forms suitable for food or beverage formulation.
There has been little innovation in new dosage form design such as sustained release or delayed release herbal products, patches, oral release sublingual tablets, etc. On a global level, Japanese firms have converted a large number of actives into functional food forms. But take our example from India. Curcumin, which has been studied for many health effects, has been shown to have poor bioavailability in humans, making innovative formulation or delivery technology a must.
The bottom line—if a finished product is not standardized as it leaves the production lines, stays stable on the shelf and is well available at the target sites of action in the human body, having a hot marketing claim won’t deliver results.
Animal Testing
Some firms may question the need for spending money on animal work if they are committed to investing in clinical trials. Perhaps it is less than ethical to test on animals when human research is equally possible for potentially harmless natural health products, right? Wrong. There is still plenty of research that is possible only in lab animals and not straight away or not at all in humans. Where there are specific safety concerns from traditional use or where the manufacturing process is likely to alter the ingredient dramatically, it is required by the regulators to perform some basic or extensive safety testing in animals before marketing or even human trials.
Even when animal studies are not required by regulations, in vitro and in vivo efficacy studies both offer advantages of screening several ingredients and doses of the same ingredient rapidly and more efficiently in the lab than it would be ever possible in a clinical setting. Moreover, some animal models are available that can elucidate mechanisms of actions which are difficult to reveal in simple human studies. Pharmacokinetic and bioavailability indicators can come out quicker and may be equally respectable as expensive human data.
Also, only having anecdotal data can hamstring the ability to design an appropriate clinical study protocol. Human studies can be expensive, even if off-shored. For clinical trials to be successful and cost-effective, the trial objectives need to be focused. Animal study results can provide this single-point focus to permit the development of a clinical study protocol that is likely to generate a positive outcome. This industry has a history of presumably good products failing in the clinic due to over-ambitious or poorly conceived trial objectives within the constraints of limited resources of time and money.
There are several possible approaches for nutraceutical product development, not one single path as is generally the case with pharmaceuticals. A balanced approach of doing some preclinicals before, during and after the clinical phase of research is prudent. But, each product is different. In some cases, it might be worth running a small pilot human study before doing any preclinical work; however, sample size being small in such a study, one must be prepared to forgo using this data for regulatory purposes. In certain cases, human studies may be more easily set up and in cases such as where “quality of life” is the research endpoint, only a human study will do. There can be many reasons for not doing extensive animal work before getting into clinical trials, but there are not many for avoiding formulation development totally. Typically clinical trials last for longer than a year. A non-uniform or an unstable product going out to human subjects in a study over several months has a potential to create chaos and not authentic and reliable data.
Clinical trial data can be a good tool for differentiating a new or existing product in the crowded market. But it may not be the right time to rush in and pluck this fruit yet. Discuss with your scientific team and outsourcing partners and time it right. An early start on a holistic approach to product development is more likely to yield results in the long run rather than ad hoc decisions on a clinical trial just because the competition has done one. A good dialogue between the preclinical and the clinical teams, set up at an early stage, can be a fair determinant of success. A regulatory expert to guide on research and business strategy can be an added benefit. In this light, contract research organizations (CROs) offering a single point management of the regulatory affairs and preclinical and clinical research programs offer a huge benefit.
Jayesh Chaudhary, is CEO of Vedic Lifesciences Pvt. Ltd., a contract research organization serving the pharmaceutical, phytopharma and nutraceutical industries; contact him atjayesh.chaudhary@vediclifesciences.com .
A clinical trial is considered low-hanging fruit in the dietary supplement industry, yielding immediate marketing value. Other types of data to support claims for a health ingredient or supplement are not as glamorous or accretive to the bottom line. Ideally, consumers want to know whether a product works on them and not just in animals. Regulators even specify controlled human studies are the gold standard for evidence of efficacy of health ingredients or drugs.
Before nutraceutical firms started to look at clinical trials in a big way, product marketers relied on testimonials from satisfied consumers and health care practitioners. Today, companies are increasingly dedicated to clinical trials; however, two types of preclinical research—“Formulation & Analytical Development” and “Animal Pharmacology & Toxicology”—are important, although the investment can seem costlier than the results.
Formulation & Analytical Development
As an example, suppose you have a novel compound from India that you want to market globally. Traditional knowledge and some in-house laboratory data substantiate certain health benefits. Ready to make that claim in most countries? Not without a passport.
The passport is a review of the finished product’s quality. Ingredient certificates of analysis (C of A) provide details on the ingredient itself; however, formulation and production steps ranging from granulation to tableting can impact the compound. Further, novel delivery systems and dosage forms also affect an ingredient’s bioavailability and stability.
On a global level, innovation in novel nutraceutical dosage forms has been slow, although some actives have been converted into forms suitable for food or beverage formulation.
There has been little innovation in new dosage form design such as sustained release or delayed release herbal products, patches, oral release sublingual tablets, etc. On a global level, Japanese firms have converted a large number of actives into functional food forms. But take our example from India. Curcumin, which has been studied for many health effects, has been shown to have poor bioavailability in humans, making innovative formulation or delivery technology a must.
The bottom line—if a finished product is not standardized as it leaves the production lines, stays stable on the shelf and is well available at the target sites of action in the human body, having a hot marketing claim won’t deliver results.
Animal Testing
Some firms may question the need for spending money on animal work if they are committed to investing in clinical trials. Perhaps it is less than ethical to test on animals when human research is equally possible for potentially harmless natural health products, right? Wrong. There is still plenty of research that is possible only in lab animals and not straight away or not at all in humans. Where there are specific safety concerns from traditional use or where the manufacturing process is likely to alter the ingredient dramatically, it is required by the regulators to perform some basic or extensive safety testing in animals before marketing or even human trials.
Even when animal studies are not required by regulations, in vitro and in vivo efficacy studies both offer advantages of screening several ingredients and doses of the same ingredient rapidly and more efficiently in the lab than it would be ever possible in a clinical setting. Moreover, some animal models are available that can elucidate mechanisms of actions which are difficult to reveal in simple human studies. Pharmacokinetic and bioavailability indicators can come out quicker and may be equally respectable as expensive human data.
Also, only having anecdotal data can hamstring the ability to design an appropriate clinical study protocol. Human studies can be expensive, even if off-shored. For clinical trials to be successful and cost-effective, the trial objectives need to be focused. Animal study results can provide this single-point focus to permit the development of a clinical study protocol that is likely to generate a positive outcome. This industry has a history of presumably good products failing in the clinic due to over-ambitious or poorly conceived trial objectives within the constraints of limited resources of time and money.
There are several possible approaches for nutraceutical product development, not one single path as is generally the case with pharmaceuticals. A balanced approach of doing some preclinicals before, during and after the clinical phase of research is prudent. But, each product is different. In some cases, it might be worth running a small pilot human study before doing any preclinical work; however, sample size being small in such a study, one must be prepared to forgo using this data for regulatory purposes. In certain cases, human studies may be more easily set up and in cases such as where “quality of life” is the research endpoint, only a human study will do. There can be many reasons for not doing extensive animal work before getting into clinical trials, but there are not many for avoiding formulation development totally. Typically clinical trials last for longer than a year. A non-uniform or an unstable product going out to human subjects in a study over several months has a potential to create chaos and not authentic and reliable data.
Clinical trial data can be a good tool for differentiating a new or existing product in the crowded market. But it may not be the right time to rush in and pluck this fruit yet. Discuss with your scientific team and outsourcing partners and time it right. An early start on a holistic approach to product development is more likely to yield results in the long run rather than ad hoc decisions on a clinical trial just because the competition has done one. A good dialogue between the preclinical and the clinical teams, set up at an early stage, can be a fair determinant of success. A regulatory expert to guide on research and business strategy can be an added benefit. In this light, contract research organizations (CROs) offering a single point management of the regulatory affairs and preclinical and clinical research programs offer a huge benefit.
Jayesh Chaudhary, is CEO of Vedic Lifesciences Pvt. Ltd., a contract research organization serving the pharmaceutical, phytopharma and nutraceutical industries; contact him atjayesh.chaudhary@vediclifesciences.com .
DESIGN THE STUDY RIGHT – MAKE YOUR SUPPLEMENTARY DREAMS COME TRUE
The story so far…….
Once upon a time, nutraceutical and functional food manufacturers lived and thrived in an unregulated world. Their products addressed a variety of health concerns and came with either implied or overt assurances of safety and efficacy. Sales were good and incidents of side effects or lack of efficacy went unquestioned. As these products did not fall into the ‘drugs’ category, they did not come under the purview of existing drug regulations which demanded proof of safety and efficacy of the drug before it reached the consumer. The creation of a ‘market’ for nutraceuticals was the next best thing that happened to manufacturers since sliced bread.
But now….
Unfortunately, like all fairy tales, this one too came to an end. Law makers stepped in and introduced systems for safeguarding the health and pockets of consumers. Writing a nutraceutical’s success story began to seem like a distant dream.
Dietary supplement (DS) and functional food (FF) manufacturers today are under scrutiny to ensure that they churn out products which really do what they say they do. Simultaneously, they have to race against time to reach the market as soon as possible. Given that the number of DS and FF products lining retail shelves is ballooning everyday, one can well understand their concerns.
As if getting adequate returns on investment on developing the product wasn’t difficult enough, DS and FF manufacturers today have to contend with grabbing a slice of the market. Add to it the fact that in premium markets like the US and the EU, because claim policing authorities are on a 24x7 vigil to trim or eliminate unsubstantiated claims, manufacturers can hardly afford to sit back and relax hoping their coffers would get replenished with no questions asked.
The problem - Regulatory Dragnets
In December 2006, EU decision makers adopted Regulation (EC) no. 1924/20061 to ensure that any nutrition and health claims made on a food label in the EU is clear and substantiated by scientific evidence which would be verified by EFSA (The European Food Safety Authority).
Under the Dietary Supplement Health and Education (DSHEA) Act of 1994, FDA has jurisdiction over the safety and labeling of dietary supplements while the FTC has jurisdiction over advertisements for dietary supplements2 Section 403(r)(6) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 343(r)(6)) requires that a manufacturer of a dietary supplement making a nutritional deficiency, structure/function, or general well-being claim have substantiation that the claim is truthful and not misleading so as to help preserve consumer confidence in his product.3
FDA can either refuse to allow new ingredients into or remove existing ingredients from the marketplace for safety reasons. The label of a dietary supplement product is required to be truthful and not misleading. If the label does not meet this requirement, FDA may remove the product from the marketplace or take other appropriate actions.
The case is quite similar even in other markets around the world where regulators demand to see proof that such products work and are safe to use for the duration of the health condition they address.
If you thought getting regulatory go-aheads was easy, think again! Recently, the USFDA refused a claim for lutein (eye health) 4 EFSA too has a tough image regarding its role in assessing data for claim substantiation. In fact, industry experts feel it’s a notch tougher than even the USFDA. Apparently, only about 2% 5 of the scientific papers presented on clinical trials on nutraceuticals survive the regulatory check post. The reasons for rejection are many, some being poor study design, short treatment duration and too few compliant subjects to allow a sound statistical analysis. Lack of product standardization and other quality issues have also contributed to this failure of data acceptance. The amount of time and money lost due to lack of adequate foresight and planning is heart-wrenching since this could have been well avoided.
Thus DS and FF have to literally go on trial in the regulators’ courts and undergo cross-examination of their efficacy and safety. It is only the quantum and strength of scientific evidence derived from clinical trials that can help manufacturers either win or lose their case and put their products in the hands of consumers or face the penalty of holding back or withdrawing their products from the market.
The solution – CRO assistance
Facing such trials would become easier with the technical and operational support of a Contract Research Organization (CRO). CROs can design and undertake the necessary clinical trials to help DS and FF manufacturers successful in generating the necessary body of evidence to back their product’s label claims in the market they wish to enter.
Evaluating dietary supplements and functional foods requires a different approach as compared to pharmaceuticals in order to ensure that the data generated on the product’s safety and efficacy is scientific and adequate without being unduly excessive and untailored to cater to the need of backing the specific claims the manufacturer wishes to make.
The cost of researching and developing a nutraceutical is lesser than that of a pharmaceutical whether in India or abroad 6 However, the Return on Investment (ROI) on nutraceuticals is also substantially less as compared to that of the latter. One major strategy in maximizing profits then is to cut costs. This can be best achieved by ensuring that the cost of the clinical trial and the time required to generate the necessary evidence for backing claims is tightly controlled. This is easier said than done. Any manufacturer without adequate experience in conducting clinical trials is bound to find the hurdles involved in the process daunting, if not defeating. The costs of conducting studies can be enormous for the uninitiated sponsor. Similarly, the time spent in completing the whole project would put him at a disadvantage as compared to his competitors in reaching the market, not to mention the costs of lost opportunity he would have to bear.
The advantage of using a CRO lies in faster recruitment, and the flexibility it affords by providing additional capacity or expertise in different therapeutic areas. A CRO with strong capabilities and a rich experience in conducting clinical trials (CTs) on nutraceuticals can make all the difference in ensuring that the sponsor has a zero headache deal on obtaining the necessary data for his product within stringent timelines and costs. Vetting the product’s identity, purity and capability and the sponsor’s need to make specific claims requires a thorough understanding of the science behind herbal and other traditional forms of health supplements.
Maintaining your wallet’s health - Offshoring
Having extolled the virtues of CROs then, here is a piece of advice for DS and FF manufacturers in the US / EU and other countries in the West – offshore your clinical trials – it will translate into further savings in time and cost. Countries like India and China today are a hub for clinical trials.
India especially with its diverse patient pool, GCP-trained investigators with specialized knowledge in their specific therapeutic areas, English speaking Clinical Trial personnel, cutting edge laboratory and data capture technology and low man-hour costs are the best bet for a sponsor wishing to minimize costs in product research.
The cost of conducting clinical trials on pharmaceutical products in India is roughly 50% of the cost of the trial when conducted in the US 7 or probably even in the EU. One can then extrapolate this finding to nutraceutical research and development and expect similar if not more reduction in costs in India as compared to the western world.
The strategy – A robust trial design that keeps the end in view
The importance of a well planned, well designed trial in determining the ultimate success of the product cannot be emphasized enough. Only a CRO with expertise in CTs on nutraceuticals can know just how to tweak the study design and manage it operationally to ensure positive outcomes that when collated into a report at the end of the study provide loud and clear evidence on the product’s claims. All this, without compromising on the safety and welfare of the trial subjects and the quality of data generated. Generation of data which would be acceptable to regulators reflects the expertise of a well experienced CRO, as this focus is necessary right from the outset while planning and designing the study.
The design of a nutraceutical trial has a very important role to play in ensuring study outcomes which could have a bearing on the advancement of health and wellness therapies and quality of life standards for patients with various afflictions. Double blind randomized placebo or active comparator controlled clinical trials are the gold standard for generating evidence about the safety and efficacy of a product. Choosing such and closely modified study designs can provide invaluable insights in improving the quality of healthcare. Randomization introduces measures of eliminating bias in treatment allocations. However, a poorly designed randomized trial will not generate credible and useful data on the product as would a well-designed study.
The success of a research trial depends on many factors and the overall strategy that carefully takes them all into consideration. However, the strategy to designing a good trial should be based on the question that one needs to ask regarding the dietary supplement to be evaluated. In his article on research in clinical practice, Dr. Arun Nanivadekar, Former Medical and Research Director, Pfizer India, writes, “The process of research has two aspects: getting an idea is one, and verifying it is the other.” 8 Getting the idea equates with generating the question that would need verification via a trial. Although at times one might find that the research question that ought to be answered is a tough nut to crack, it is imperative that one avoids the easy way out by asking an easier but a useless or a less useful question. Having asked the right question is the first step to designing the trial to get the right answers and to ensure study success.
To quote Jayesh Chaudhary, Founder and CEO of Vedic Lifesciences, a CRO specializing in nutraceutical claim substantiation trials, “Determining the primary question to be asked in a clinical trial of a dietary supplement is critical to its success. Ask a wrong question and you end up with the wrong answer, no answer or an answer that has no market or regulatory value.” 9 Thus in a nutshell, a well designed study can provide the answers to support nutraceutical label claims while maintaining an optimal cost/ benefit ratio thus maximizing profits while minimizing costs.
Making your product’s fairy tale have a happy ending is possible without incurring financial nightmares. Choosing the right CRO and thereby the best study design, is the best way to go about it.
Dr. Aliya Shakeel is Medical Writer at Vedic Lifesciences Pvt. Ltd. For more information on growing yournutraceutical business you can reach her at vedic@vediclifesciences.com or on +91 22 42025703
References
1) Food Science and Technology Ireland Publication of the Institute of Food Science and Technology, Ireland
Volume 2, September 2008
www.icmsf.iit.edu/pdf/FoodScienceTechnologyIrelandVol2-2008.PDF
2) Brackett R. : The Regulation of Dietary Supplements: A Review of Consumer Safeguards
March 9, 2006
http://www.fda.gov/NewsEvents/Testimony/ucm112576.htm
3) Guidance for Industry: Substantiation for Dietary Supplement Claims Made Under Section 403(r) (6) of the Federal Food, Drug, and Cosmetic Act December 2008
http://www.fda.gov/Food/.../ucm073200.htm
4) Qualified Health Claims: Letter of Denial - Xangold® Lutein Esters, Lutein, or Zeaxanthin and Reduced Risk of Age-related Macular Degeneration or Cataract Formation (Docket No. 2004Q-0180)
December 19, 2005
http://www.fda.gov/Food/LabelingNutrition/LabelClaims/QualifiedHealthClaims/ucm073291.htm
5) Berry P: EU health claims and accompanying legislation - time lines
Nutraceuticals International June 01, 2006
http://www.accessmylibrary.com/coms2/summary_0286-15771927_ITM
6) A G Pise, D Sreedhar, M Janodia, V Ligade & N Udupa : Changing paradigms in drug discovery
November 27, 2008
http://www.pharmabiz.com/article/detnews.asp?articleid=47207§ionid=50
7) Clinical trials are now increasingly outsourced to developing countries like India
http://www.offshoringtimes.com/Pages/2006/BPO_news926.html
8) Dr. Nanivadekar A : On research in clinical practice Perspective in clinical research official publication of the Indian Society for clinical research
9) Chaudhari J: Selecting Health Claims for Nutraceutical Clinical Trials
Natural Products Insider 12/21/09
http://www.naturalproductsinsider.com/articles/2009/12/selecting-health-claims-for- nutraceutical-clinical- trials.aspx
Once upon a time, nutraceutical and functional food manufacturers lived and thrived in an unregulated world. Their products addressed a variety of health concerns and came with either implied or overt assurances of safety and efficacy. Sales were good and incidents of side effects or lack of efficacy went unquestioned. As these products did not fall into the ‘drugs’ category, they did not come under the purview of existing drug regulations which demanded proof of safety and efficacy of the drug before it reached the consumer. The creation of a ‘market’ for nutraceuticals was the next best thing that happened to manufacturers since sliced bread.
But now….
Unfortunately, like all fairy tales, this one too came to an end. Law makers stepped in and introduced systems for safeguarding the health and pockets of consumers. Writing a nutraceutical’s success story began to seem like a distant dream.
Dietary supplement (DS) and functional food (FF) manufacturers today are under scrutiny to ensure that they churn out products which really do what they say they do. Simultaneously, they have to race against time to reach the market as soon as possible. Given that the number of DS and FF products lining retail shelves is ballooning everyday, one can well understand their concerns.
As if getting adequate returns on investment on developing the product wasn’t difficult enough, DS and FF manufacturers today have to contend with grabbing a slice of the market. Add to it the fact that in premium markets like the US and the EU, because claim policing authorities are on a 24x7 vigil to trim or eliminate unsubstantiated claims, manufacturers can hardly afford to sit back and relax hoping their coffers would get replenished with no questions asked.
The problem - Regulatory Dragnets
In December 2006, EU decision makers adopted Regulation (EC) no. 1924/20061 to ensure that any nutrition and health claims made on a food label in the EU is clear and substantiated by scientific evidence which would be verified by EFSA (The European Food Safety Authority).
Under the Dietary Supplement Health and Education (DSHEA) Act of 1994, FDA has jurisdiction over the safety and labeling of dietary supplements while the FTC has jurisdiction over advertisements for dietary supplements2 Section 403(r)(6) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 343(r)(6)) requires that a manufacturer of a dietary supplement making a nutritional deficiency, structure/function, or general well-being claim have substantiation that the claim is truthful and not misleading so as to help preserve consumer confidence in his product.3
FDA can either refuse to allow new ingredients into or remove existing ingredients from the marketplace for safety reasons. The label of a dietary supplement product is required to be truthful and not misleading. If the label does not meet this requirement, FDA may remove the product from the marketplace or take other appropriate actions.
The case is quite similar even in other markets around the world where regulators demand to see proof that such products work and are safe to use for the duration of the health condition they address.
If you thought getting regulatory go-aheads was easy, think again! Recently, the USFDA refused a claim for lutein (eye health) 4 EFSA too has a tough image regarding its role in assessing data for claim substantiation. In fact, industry experts feel it’s a notch tougher than even the USFDA. Apparently, only about 2% 5 of the scientific papers presented on clinical trials on nutraceuticals survive the regulatory check post. The reasons for rejection are many, some being poor study design, short treatment duration and too few compliant subjects to allow a sound statistical analysis. Lack of product standardization and other quality issues have also contributed to this failure of data acceptance. The amount of time and money lost due to lack of adequate foresight and planning is heart-wrenching since this could have been well avoided.
Thus DS and FF have to literally go on trial in the regulators’ courts and undergo cross-examination of their efficacy and safety. It is only the quantum and strength of scientific evidence derived from clinical trials that can help manufacturers either win or lose their case and put their products in the hands of consumers or face the penalty of holding back or withdrawing their products from the market.
The solution – CRO assistance
Facing such trials would become easier with the technical and operational support of a Contract Research Organization (CRO). CROs can design and undertake the necessary clinical trials to help DS and FF manufacturers successful in generating the necessary body of evidence to back their product’s label claims in the market they wish to enter.
Evaluating dietary supplements and functional foods requires a different approach as compared to pharmaceuticals in order to ensure that the data generated on the product’s safety and efficacy is scientific and adequate without being unduly excessive and untailored to cater to the need of backing the specific claims the manufacturer wishes to make.
The cost of researching and developing a nutraceutical is lesser than that of a pharmaceutical whether in India or abroad 6 However, the Return on Investment (ROI) on nutraceuticals is also substantially less as compared to that of the latter. One major strategy in maximizing profits then is to cut costs. This can be best achieved by ensuring that the cost of the clinical trial and the time required to generate the necessary evidence for backing claims is tightly controlled. This is easier said than done. Any manufacturer without adequate experience in conducting clinical trials is bound to find the hurdles involved in the process daunting, if not defeating. The costs of conducting studies can be enormous for the uninitiated sponsor. Similarly, the time spent in completing the whole project would put him at a disadvantage as compared to his competitors in reaching the market, not to mention the costs of lost opportunity he would have to bear.
The advantage of using a CRO lies in faster recruitment, and the flexibility it affords by providing additional capacity or expertise in different therapeutic areas. A CRO with strong capabilities and a rich experience in conducting clinical trials (CTs) on nutraceuticals can make all the difference in ensuring that the sponsor has a zero headache deal on obtaining the necessary data for his product within stringent timelines and costs. Vetting the product’s identity, purity and capability and the sponsor’s need to make specific claims requires a thorough understanding of the science behind herbal and other traditional forms of health supplements.
Maintaining your wallet’s health - Offshoring
Having extolled the virtues of CROs then, here is a piece of advice for DS and FF manufacturers in the US / EU and other countries in the West – offshore your clinical trials – it will translate into further savings in time and cost. Countries like India and China today are a hub for clinical trials.
India especially with its diverse patient pool, GCP-trained investigators with specialized knowledge in their specific therapeutic areas, English speaking Clinical Trial personnel, cutting edge laboratory and data capture technology and low man-hour costs are the best bet for a sponsor wishing to minimize costs in product research.
The cost of conducting clinical trials on pharmaceutical products in India is roughly 50% of the cost of the trial when conducted in the US 7 or probably even in the EU. One can then extrapolate this finding to nutraceutical research and development and expect similar if not more reduction in costs in India as compared to the western world.
The strategy – A robust trial design that keeps the end in view
The importance of a well planned, well designed trial in determining the ultimate success of the product cannot be emphasized enough. Only a CRO with expertise in CTs on nutraceuticals can know just how to tweak the study design and manage it operationally to ensure positive outcomes that when collated into a report at the end of the study provide loud and clear evidence on the product’s claims. All this, without compromising on the safety and welfare of the trial subjects and the quality of data generated. Generation of data which would be acceptable to regulators reflects the expertise of a well experienced CRO, as this focus is necessary right from the outset while planning and designing the study.
The design of a nutraceutical trial has a very important role to play in ensuring study outcomes which could have a bearing on the advancement of health and wellness therapies and quality of life standards for patients with various afflictions. Double blind randomized placebo or active comparator controlled clinical trials are the gold standard for generating evidence about the safety and efficacy of a product. Choosing such and closely modified study designs can provide invaluable insights in improving the quality of healthcare. Randomization introduces measures of eliminating bias in treatment allocations. However, a poorly designed randomized trial will not generate credible and useful data on the product as would a well-designed study.
The success of a research trial depends on many factors and the overall strategy that carefully takes them all into consideration. However, the strategy to designing a good trial should be based on the question that one needs to ask regarding the dietary supplement to be evaluated. In his article on research in clinical practice, Dr. Arun Nanivadekar, Former Medical and Research Director, Pfizer India, writes, “The process of research has two aspects: getting an idea is one, and verifying it is the other.” 8 Getting the idea equates with generating the question that would need verification via a trial. Although at times one might find that the research question that ought to be answered is a tough nut to crack, it is imperative that one avoids the easy way out by asking an easier but a useless or a less useful question. Having asked the right question is the first step to designing the trial to get the right answers and to ensure study success.
To quote Jayesh Chaudhary, Founder and CEO of Vedic Lifesciences, a CRO specializing in nutraceutical claim substantiation trials, “Determining the primary question to be asked in a clinical trial of a dietary supplement is critical to its success. Ask a wrong question and you end up with the wrong answer, no answer or an answer that has no market or regulatory value.” 9 Thus in a nutshell, a well designed study can provide the answers to support nutraceutical label claims while maintaining an optimal cost/ benefit ratio thus maximizing profits while minimizing costs.
Making your product’s fairy tale have a happy ending is possible without incurring financial nightmares. Choosing the right CRO and thereby the best study design, is the best way to go about it.
Dr. Aliya Shakeel is Medical Writer at Vedic Lifesciences Pvt. Ltd. For more information on growing yournutraceutical business you can reach her at vedic@vediclifesciences.com or on +91 22 42025703
References
1) Food Science and Technology Ireland Publication of the Institute of Food Science and Technology, Ireland
Volume 2, September 2008
www.icmsf.iit.edu/pdf/FoodScienceTechnologyIrelandVol2-2008.PDF
2) Brackett R. : The Regulation of Dietary Supplements: A Review of Consumer Safeguards
March 9, 2006
http://www.fda.gov/NewsEvents/Testimony/ucm112576.htm
3) Guidance for Industry: Substantiation for Dietary Supplement Claims Made Under Section 403(r) (6) of the Federal Food, Drug, and Cosmetic Act December 2008
http://www.fda.gov/Food/.../ucm073200.htm
4) Qualified Health Claims: Letter of Denial - Xangold® Lutein Esters, Lutein, or Zeaxanthin and Reduced Risk of Age-related Macular Degeneration or Cataract Formation (Docket No. 2004Q-0180)
December 19, 2005
http://www.fda.gov/Food/LabelingNutrition/LabelClaims/QualifiedHealthClaims/ucm073291.htm
5) Berry P: EU health claims and accompanying legislation - time lines
Nutraceuticals International June 01, 2006
http://www.accessmylibrary.com/coms2/summary_0286-15771927_ITM
6) A G Pise, D Sreedhar, M Janodia, V Ligade & N Udupa : Changing paradigms in drug discovery
November 27, 2008
http://www.pharmabiz.com/article/detnews.asp?articleid=47207§ionid=50
7) Clinical trials are now increasingly outsourced to developing countries like India
http://www.offshoringtimes.com/Pages/2006/BPO_news926.html
8) Dr. Nanivadekar A : On research in clinical practice Perspective in clinical research official publication of the Indian Society for clinical research
9) Chaudhari J: Selecting Health Claims for Nutraceutical Clinical Trials
Natural Products Insider 12/21/09
http://www.naturalproductsinsider.com/articles/2009/12/selecting-health-claims-for- nutraceutical-clinical- trials.aspx
Maximizing Profit for Nutraceutical Firms
The Nutraceutical market worldwide is expected to reach USD 177 billion by 2013, growing at a CAGR of 7%, driven by the fastest growing category of dietary supplements.1
Are the small/medium sized enterprises (SME) going to participate in this growth equally or will they be left out of the party? Having worked for the last decade with a number of such SMEs, Vedic Lifesciences has some insight to share. We shall discuss possible strategies to help Nutraceutical SMEs grow rapidly in the future.
Revenue growth by any firm could be achieved a) by going global, b) by growing sales within the domestic markets or c) by improving product life spans through constant investments in the value offered to the consumer. Bottom-lines can be improved by ensuring that at least some brands in the portfolio can command a premium pricing.
Growth by Going Global :
There may be challenges to domestic sales growth as competition from similar brands becomes fiercer and/or the distribution network becomes a bottleneck. On the other hand, going global requires an understanding of the foreign regulations and market conditions and the ability to identify and grow partnerships. Its imperative to partner with foreign companies who have the required regulatory expertise and marketing muscle to smartly overcome the deficiencies of the brand-owner company. A big opportunity to maximize profits is by moving up the “regulatory value chain”, meaning getting the same brand approved in a tougher regulatory atmosphere using supporting R&D data. Example, a manufacturer of a dietary supplement that is able to make only health claims in US can get the same product approved as a Natural Health Product in Canada and make medicine like claims. Importers will always prefer a brand that is already established in markets elsewhere provided the product can meet higher regulatory requirements in the importing country. Having an R&D dossier that was planned and compiled well will go a long way in establishing newer and rewarding markets in economies that may be doing better than the home market.
Domestic Growth:
Relaunching old brands in the domestic markets is a tougher challenge without a new marketing partner or infusion of new value into the product through R&D. Several global economies are still recovering, yet consumer choices for supplements and health foods are huge. In such a scenario, brands that don’t offer value will be wiped out. The cost of a well-conceived preclinical or even clinical program is still lower than an advertising campaign that companies spend on. But an ad can be only as good as the product it sells. A good ad will sell a bad product too, but only for a while. Whereas a good product doesn’t require much ad spend at all in today’s highly democratic and networked consumer world of social media and Web 2.0. Hence companies that do their own domestic marketing of wellness products may consider setting aside at least 50% of their previous year’s marketing and promotional budgets for R&D for the next 3 consecutive years.
Growth by Lifespan Extension:
History of health and wellness brands in most of the regulated world has shown that brands that are well-entrenched in the minds of the consumer psyche had a strong value proposition for the consumer in the first years of their launch. Value can be created through multiple ways and a universal technique remains evidence of health benefit or clinical efficacy. Stronger brands always last a lifetime and sometimes span several generations of consumers. Age-old Nutra brands can be ever-greened through continual R&D.
Profit Growth through Premium Pricing:
Only with innovation and value addition can a dietary supplement or health food rise above the clutter of other me-too brands. Consumers clearly will pay a dollar more for any specific and proven value over the other brands available. Intelligent R&D and smart marketing: neither can do without the other. Investment in only one of them without concurrent focus on the other can lead to disappointments in the short or long run.
The Road to Success via Product Innovation:
When all roads to business success seem to be going via product innovation, it is imperative to have a highly efficient R&D process in-house or outsource it to the most experienced and effective partner. A big reason why SMEs have shied away from own R&D so far in the nutraceutical industry worldwide is the wrong perception that R&D is risky and costly. R&D success must be ensured and costs contained for SMEs to be able to participate fully in the market growth that we are likely to witness in the Health and Wellness markets worldwide in the present decade. Research methods used by pharma do not offer the promise of risk-reduction and cost efficiency that nutraceutical companies look for. Nutraceutical companies need special research methods 2 , 3They must engage (early in the research program) a CRO that has the special skills and experience to handle such challenges specific to the natural product industry in order to participate in the competitive marketplace of wellness products today. Care must be taken that all research is compliant to the global regulations for such natural products. It must be further noted that the toughest global regulations for preclinical and clinical evidence for natural products are not difficult to comply with and are certainly not akin to drug regulations.
Cost-effective, speedy and compliant science is the starting point for building a great health and wellness brand for the world markets and maximizing ROIs in this sector.
Jayesh Chaudhary is Founder & Managing Director of Vedic Lifesciences Pvt. Ltd. For more information on growing your nutraceutical business you can reach him at vedic@vediclifesciences.com
or on +91 9821086665
References:
1. Ernst & Young, FICCI: NUTRACEUTICALS - Critical supplement for building a healthy India.
www.ficci-nutraceuticals.com
2. Chaudhary J: Is My Product Ready for Clinical Trials
Natural Products Insider Nov 23, 2009
www.naturalproductsinsider.com
3. Chaudhary J: Selecting Health Claims for Nutraceutical Clinical Trials
Natural Products Insider Dec 21, 2009.
www.naturalproductsinsider.com
Are the small/medium sized enterprises (SME) going to participate in this growth equally or will they be left out of the party? Having worked for the last decade with a number of such SMEs, Vedic Lifesciences has some insight to share. We shall discuss possible strategies to help Nutraceutical SMEs grow rapidly in the future.
Revenue growth by any firm could be achieved a) by going global, b) by growing sales within the domestic markets or c) by improving product life spans through constant investments in the value offered to the consumer. Bottom-lines can be improved by ensuring that at least some brands in the portfolio can command a premium pricing.
Growth by Going Global :
There may be challenges to domestic sales growth as competition from similar brands becomes fiercer and/or the distribution network becomes a bottleneck. On the other hand, going global requires an understanding of the foreign regulations and market conditions and the ability to identify and grow partnerships. Its imperative to partner with foreign companies who have the required regulatory expertise and marketing muscle to smartly overcome the deficiencies of the brand-owner company. A big opportunity to maximize profits is by moving up the “regulatory value chain”, meaning getting the same brand approved in a tougher regulatory atmosphere using supporting R&D data. Example, a manufacturer of a dietary supplement that is able to make only health claims in US can get the same product approved as a Natural Health Product in Canada and make medicine like claims. Importers will always prefer a brand that is already established in markets elsewhere provided the product can meet higher regulatory requirements in the importing country. Having an R&D dossier that was planned and compiled well will go a long way in establishing newer and rewarding markets in economies that may be doing better than the home market.
Domestic Growth:
Relaunching old brands in the domestic markets is a tougher challenge without a new marketing partner or infusion of new value into the product through R&D. Several global economies are still recovering, yet consumer choices for supplements and health foods are huge. In such a scenario, brands that don’t offer value will be wiped out. The cost of a well-conceived preclinical or even clinical program is still lower than an advertising campaign that companies spend on. But an ad can be only as good as the product it sells. A good ad will sell a bad product too, but only for a while. Whereas a good product doesn’t require much ad spend at all in today’s highly democratic and networked consumer world of social media and Web 2.0. Hence companies that do their own domestic marketing of wellness products may consider setting aside at least 50% of their previous year’s marketing and promotional budgets for R&D for the next 3 consecutive years.
Growth by Lifespan Extension:
History of health and wellness brands in most of the regulated world has shown that brands that are well-entrenched in the minds of the consumer psyche had a strong value proposition for the consumer in the first years of their launch. Value can be created through multiple ways and a universal technique remains evidence of health benefit or clinical efficacy. Stronger brands always last a lifetime and sometimes span several generations of consumers. Age-old Nutra brands can be ever-greened through continual R&D.
Profit Growth through Premium Pricing:
Only with innovation and value addition can a dietary supplement or health food rise above the clutter of other me-too brands. Consumers clearly will pay a dollar more for any specific and proven value over the other brands available. Intelligent R&D and smart marketing: neither can do without the other. Investment in only one of them without concurrent focus on the other can lead to disappointments in the short or long run.
The Road to Success via Product Innovation:
When all roads to business success seem to be going via product innovation, it is imperative to have a highly efficient R&D process in-house or outsource it to the most experienced and effective partner. A big reason why SMEs have shied away from own R&D so far in the nutraceutical industry worldwide is the wrong perception that R&D is risky and costly. R&D success must be ensured and costs contained for SMEs to be able to participate fully in the market growth that we are likely to witness in the Health and Wellness markets worldwide in the present decade. Research methods used by pharma do not offer the promise of risk-reduction and cost efficiency that nutraceutical companies look for. Nutraceutical companies need special research methods 2 , 3They must engage (early in the research program) a CRO that has the special skills and experience to handle such challenges specific to the natural product industry in order to participate in the competitive marketplace of wellness products today. Care must be taken that all research is compliant to the global regulations for such natural products. It must be further noted that the toughest global regulations for preclinical and clinical evidence for natural products are not difficult to comply with and are certainly not akin to drug regulations.
Cost-effective, speedy and compliant science is the starting point for building a great health and wellness brand for the world markets and maximizing ROIs in this sector.
Jayesh Chaudhary is Founder & Managing Director of Vedic Lifesciences Pvt. Ltd. For more information on growing your nutraceutical business you can reach him at vedic@vediclifesciences.com
or on +91 9821086665
References:
1. Ernst & Young, FICCI: NUTRACEUTICALS - Critical supplement for building a healthy India.
www.ficci-nutraceuticals.com
2. Chaudhary J: Is My Product Ready for Clinical Trials
Natural Products Insider Nov 23, 2009
www.naturalproductsinsider.com
3. Chaudhary J: Selecting Health Claims for Nutraceutical Clinical Trials
Natural Products Insider Dec 21, 2009.
www.naturalproductsinsider.com
Tuesday, August 25, 2009
Ethics Committees in India have come a long way
Around 2004 when I asked a friend from Pfizer Outcomes Research the hassles of conducting phase trials in
“Transparency and accountability in (Indian Medical) research currently depends on individual institution which may have allegiance to different groups, and may be in need for benefits from Sponsors. (Indian) IECs are used to closed door meetings and generally communications from IECs focus on final decisions without specifying reasons or information on how to improve the research study to the researchers”
But that was 2006. In mid-2009, while the Medical Research Ethics Committees in
FERCI
The Forum for Ethical Review Committee in India (FERCI) was formed in Dec 2002 as the Indian chapter of FERCAP. It was not very active for a few years after formation but has recently been rejuvenated and one of its recent initiatives is IEC accreditations in
- Establish & foster communication between IECs in
- Act as a national collaborating agency for ethics reviews
- Organize & facilitate meetings, trainings & symposia on ethical review processes
- Assist in the development & implementation of SOPs for ethical review based on WHO guidelines
- Co-ordinate national communications & issues with other global bodies
CTRI
The Indian Clinical Trial Registry is available / encouraged for all clinical research except Bioavailability and Observational trials. Registration is free and presently can be done for on-going studies also. CTRI registration requires some parameters beyond the WHO recommendation that may be essential from an Indian perspective. For example, name of the IECs/ Institutional Review Boards (IRBs) that have approved the study/sites and DCGI approval status are required. Later, CTRI may even insist on approvals from accredited IECs. Conversely, not all IECs in
ICMR guidelines for IECs have existed since long and are by and large adopted as Standard Operating Procedures (SOPs) by most IECs in
Jayesh Chaudhary
CEO
VEDIC LIFESCIENCES P LTD
Ethical concern and associated with Oncology Clinical Trial
Cancer is arguably the most fatal disease. It is estimated that one third of drugs under discovery or development are for Oncology, but still cancer is almost incurable. Many Cancer Drugs are themselves carcinogenic or toxic. So unlike other therapeutic area’s, it is unethical and unsafe to include healthy volunteers for non-therapeutic oncology clinical trials. That is the reason why non-therapeutic clinical trials are being conducted on patients who are already suffering from this disease, but I am not sure if it is ethical to keep even cancer patients on sub-therapeutic dosage.
There are lots of developments which are taking place around the globe to reduce the timeline and number of patients, which eventually reduce the risk & pain involved during non-therapeutic oncology clinical trial. One such development is Phase 0 clinical trials, which is developed in response to the United States Food and Drug Administration’s (FDA) recent exploratory Investigational New Drug (IND) guidance, to expedite the clinical evaluation of new molecular entities. It involves lesser number of patients for shorter duration and also promises to shorten the duration of non-therapeutic trial by three to six months, i.e. the timeline for taking anticancer drugs from the laboratory to the clinic. Unlike Phase I clinical trials which are designed to establish the MTD, the Phase 0 clinical trial’s maximum dose can be that at which a PK/PD response is observed or target modulation is measured, providing that no drug-associated toxicity is found. Although it does not give any Patient benefit but it gives a flexibility to conduct Phase 1 Clinical trials at much higher dose and with less patient population.
Another significant development which took place is modified study design. The designs which are more or less in use are Accelerated Titration Designs and simulation study designs. Current phase I trials often take a long time to complete and provide little information about inter-patient variability or cumulative toxicity. These designs are developed to get the necessary information by reducing the number of patients and duration in non-therapeutic Oncology clinical trials (http://linus.nci.nih.gov/~brb/AcceleratedTitration.pdf).
Still these developments will not eliminate the suffering a patient volunteer may endure in non-therapeutic trials. Although these study designs promise that the duration of risk will be less or the number of patient volunteers involved in such studies will be less, it can not be eliminated. The main problem in drug discovery & development of oncology drug is unavailability of laboratory methods which can accurately predict which entity will be effective against a particular class of human cancer.
The patients who are suffering from such a painful disease get involved in clinical trials for a variety of reasons, which I believe is unethical. However, the conduct of non-therapeutic Oncology clinical trials is necessary for the advancement of healthcare in society. Hence I believe that the conduct of non-therapeutic clinical trials is a necessary sin, which Pharma companies & CRO have to indulge in for the benefit of society.
Dhirendra V. Singh,
Business Development Manager,
Vedic Lifesciences Pvt Ltd
bizdev@vediclifesciences.com
Monday, June 08, 2009
Oncology Clinical Trial: Long Timeline and Breakthrough
Millions of dollars are spent on creating new treatment methods for cancer. The main reason for high cost of cancer treatment method is long time, complication and cost involved in Drug Discovery and Development process. Considering the timeline and cost involved in Clinical Trial, we developed a model. This model is based a disease surveillance on cancer and studying the trends of Cancer studies. This model is developed to reduce the timeline without compromising quality and by reducing the cost.
The major area’s which we have covered in this model are Long & Unethical early stages, failure at early stages, Study design related problem like end point & study criterion, General acceptance of report and Reasons for long time line like low recruitment rate, IND complications, multiple effects, low survival rate of patients etc.
V – Onco© model has been developed to identify exact input, process and output parameters, in order to bring an effective mechanism in place. Most important aspect of any mechanism is inputs. One cannot expect perfect results without accurate inputs. According to this model, the inputs have to be provided by CRO and Sponsor. Before looking for a CRO the sponsor should have definite plan to introduce modern models for conducting trial like Phase 0, New Phase I designs for reducing the timeline and getting early indication of investigational products. Considering the complications involved in study the sponsor should ease the inclusion exclusion criterion. While selecting a CRO the sponsor must consider the knowledge base, their patent & investigators database, regulatory environment and ability to absorb the SOP.
Once selected, CRO has to play role of partner and select a site not only with high disease prevalence, experienced investigator & favorable regulatory environment but also with clinical research supportive environment. If they are lacking in some area, they help the CRO as a guide or knowledge partner and help the sponsor in selection of right partners with high patient base and knowledge base with current industry patterns. CRO can provide their best inputs through accurate and innovative research methodologies (like translational research), site selection and site feasibility.
With accurate inputs, process becomes easier with boundaries of well defined SOPs and well trained monitor. It is the responsibility of CRO to empathize with the site personnel and patient volunteers for fulfilling their needs related to clinical study. There should be a system of patient follow-up by creating validating and updating the database. There should also be a system of IP administration if patient is unable to visit. Site effectiveness should be highest in order to conduct qualitative trials with 100% source data verification.
CRO support is most crucial aspect of this process which includes complete site based support and recruitment of ICH – GCP trained physicians.
Creating awareness and marketing of suitable clinical trial is also part of the process. All these process parameters are focused on faster subject recruitment with quality data, favorable regulatory environment & understanding of clinical trials among physicians and patients. This can not be done overnight rather a continuous effort is required to achieve this goal. CRO has to conduct a disease prevalence study to know the extent of disease spread. CRO should also maintain database of Primary health centers & general physicians and create awareness about Clinical research to get their support for Volunteer recruitment, which is very vital for Cancer Studies.
Last stage of this system is a suitable output which is directly dependent on above two steps. As per V – Onco© model, with precise inputs and efficient process, one tends to get desired output in terms of faster regulatory approval, quality data, shorter timelines and better return on investment.
As industry demands quality data in most cost effective manner, we have designed V – Onco© model. Industry trends and patterns have changed due to economic slowdown which suggests cost effective research and CRO can be best partner to achieve the same.Below is model for reducing the timeline of Oncology Clinical Trials:
V – Onco© Model:
Dhirendra Vikram Singh
Business Development Manager
The major area’s which we have covered in this model are Long & Unethical early stages, failure at early stages, Study design related problem like end point & study criterion, General acceptance of report and Reasons for long time line like low recruitment rate, IND complications, multiple effects, low survival rate of patients etc.
V – Onco© model has been developed to identify exact input, process and output parameters, in order to bring an effective mechanism in place. Most important aspect of any mechanism is inputs. One cannot expect perfect results without accurate inputs. According to this model, the inputs have to be provided by CRO and Sponsor. Before looking for a CRO the sponsor should have definite plan to introduce modern models for conducting trial like Phase 0, New Phase I designs for reducing the timeline and getting early indication of investigational products. Considering the complications involved in study the sponsor should ease the inclusion exclusion criterion. While selecting a CRO the sponsor must consider the knowledge base, their patent & investigators database, regulatory environment and ability to absorb the SOP.
Once selected, CRO has to play role of partner and select a site not only with high disease prevalence, experienced investigator & favorable regulatory environment but also with clinical research supportive environment. If they are lacking in some area, they help the CRO as a guide or knowledge partner and help the sponsor in selection of right partners with high patient base and knowledge base with current industry patterns. CRO can provide their best inputs through accurate and innovative research methodologies (like translational research), site selection and site feasibility.
With accurate inputs, process becomes easier with boundaries of well defined SOPs and well trained monitor. It is the responsibility of CRO to empathize with the site personnel and patient volunteers for fulfilling their needs related to clinical study. There should be a system of patient follow-up by creating validating and updating the database. There should also be a system of IP administration if patient is unable to visit. Site effectiveness should be highest in order to conduct qualitative trials with 100% source data verification.
CRO support is most crucial aspect of this process which includes complete site based support and recruitment of ICH – GCP trained physicians.
Creating awareness and marketing of suitable clinical trial is also part of the process. All these process parameters are focused on faster subject recruitment with quality data, favorable regulatory environment & understanding of clinical trials among physicians and patients. This can not be done overnight rather a continuous effort is required to achieve this goal. CRO has to conduct a disease prevalence study to know the extent of disease spread. CRO should also maintain database of Primary health centers & general physicians and create awareness about Clinical research to get their support for Volunteer recruitment, which is very vital for Cancer Studies.
Last stage of this system is a suitable output which is directly dependent on above two steps. As per V – Onco© model, with precise inputs and efficient process, one tends to get desired output in terms of faster regulatory approval, quality data, shorter timelines and better return on investment.
As industry demands quality data in most cost effective manner, we have designed V – Onco© model. Industry trends and patterns have changed due to economic slowdown which suggests cost effective research and CRO can be best partner to achieve the same.Below is model for reducing the timeline of Oncology Clinical Trials:
V – Onco© Model:
Dhirendra Vikram Singh
Business Development Manager
Above V – Onco© is copyrighted and property of Vedic Lifesciences Pvt Ltd. It shall not be used without written consent of Vedic Lifesciences Pvt Ltd.
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About Me
- Vedic Lifesciences
- Mumbai, Maharashtra, India
- Vedic Lifesciences, a Phase II/III CRO based in India, also undertakes project management of Pre-Clinical Development Services for Pharma, Biotech and Medical Devices. We also offer the Indian advantage of cost, timeline & quality. We have an in-house team for Medical Affairs, Regulatory, Project Management and Data Management and have completed 34 trials for Sponsors in US, Germany, Netherlands, France, Hong Kong, etc., another 7 trials are on-going for approvals in various categories. Our therapeutic expertise includes: Orthopedics, Diabetes, Andrology/Urology, Cardiovascular Disorders, HIV/AIDS, Endocrinology, Lifestyle Disorders, Metabolic Disorders, Dermatology, Respiratory Disorders etc.
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