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| EDITORIAL |
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| Year : 2023 | Volume
: 55
| Issue : 3 | Page : 145-148 |
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Clinical trials for food – The gray areas: Developing countries' perspective
Praisy K Prabha, Ajay Prakash, Bikash Medhi
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| Date of Submission | 27-Jun-2023 |
| Date of Decision | 22-Jul-2023 |
| Date of Acceptance | 22-Jul-2023 |
| Date of Web Publication | 01-Aug-2023 |
Correspondence Address:
Bikash Medhi
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijp.ijp_412_23
How to cite this article:
Prabha PK, Prakash A, Medhi B. Clinical trials for food – The gray areas: Developing countries' perspective. Indian J Pharmacol 2023;55:145-8 |
| » Introduction | |  |
Novel food according to the European Commission can be defined as “any food that was not used for human consumption to a significant degree within the Union before May 15, 1997, irrespective of the dates of accession of Member States to the Union, and that falls under at least one of the 10 categories detailed in the EU regulations for novel foods.”[1] This covers new foods, food from new sources, new substances used in food as well as new ways and technologies for producing food.[1]
Similarly, foods for special medical purposes (FSMPs) are defined as “foods intended for the exclusive or partial feeding of people whose nutritional requirements cannot be met by normal foods.”[2]
The Indian Nutraceutical Industry is expected to grow from $4 billion in 2017 to $18 billion in 2025, as estimated by a 2018 Assocham knowledge report.[3],[4] Currently, there are three potential investment areas in the nutraceutical sector with respect to India, namely herbal supplements, functional foods, and foods for special dietary needs or FSDU involving vitamins, minerals, and probiotics.[5] Health supplements as per the FSSAI are defined as “a category of foods, which consists of a concentrated source of nutrients (such as proteins, minerals, vitamins, and amino acids) and/or other ingredients with nutritional or physiological effects, singly or in combination, whose purpose is to supplement the normal diet.”[6] Even though a separate category for functional foods has not been included in the FSSAI regulations, 2016, all the food categories in the regulation 2016 that have benefits exceeding the basic nutrition and may play a key role in reducing disease risk, fall in the category of “functional foods” as well as “foods for special dietary use.”[6],[7]
Approval of novel foods for the general public or a special population requires prior evidence for the claims being made about the concerned food which led to the introduction of concept of evidence-based nutrition similar to evidence-based medicine.[8],[9] Even though nutrition research has been a blooming area since 1990s, randomized controlled trials offer to be the most reliable strategy to evaluate the effects as well as the extent of credibility of the claims being made on the use of novel foods in the general population.[10]
Due to the overwhelming number of novel foods that are being introduced in the recent years at an ever-increasing rate, many countries, including Canada, Australia, New Zealand, Singapore, China, and the European Union, have laid down their guidelines for review and approval of novel foods as well as the claims being made for their consumption.[11] However, direct implementation of these guidelines in developing countries like India can be challenging, mainly due to the diverse geographical and cultural differences that prevail in the population residing here. These differences raise many ethical and safety concerns while conducting randomized controlled trials for novel foods and FSMPs in these countries, specifically, the Indian population, thereby necessitating the urgency to formulate detailed guidelines for review and approval of such foods specifically for the Indian population.
| » Clinical Trials for Drug versus Food | | |
Clinical trials for drugs are intended to assess the safety and efficacy of a drug against a particular indication and, therefore, include study participants who have been clinically diagnosed with the specific disease. Food trials, on the other hand, assess specific marketing claims being made by the sponsor/investigators and, therefore, include more broad criteria for selection of study participants who are either healthy or have mild deficiency.[12] While clinical trials are conducted in highly controlled setups, food trials can be conducted in much more free-living conditions.[12]
| » Conducting Randomized Clinical Trials for Novel Foods in the Indian Population: Challenges | | |
General concerns
- Similar to the randomized clinical trials (RCTs) for a drug intervention, the success of RCTs for novel foods requires compliance with the dietary pattern being studied.[13] This necessitates the need to ensure the tolerance of the participants to the diet/food being provided as well as the motivation/appeal to comply with the study diet pattern.[13] This can be challenging to achieve in a country like India where the general population has a wide range of food preferences based on their geographical setup as well as cultural preferences
- While it is easy to have a placebo group in RCTs for drug interventions, blinding of participants can be difficult in RCTs for novel foods as it will include change in their complete meal or taste of the meal[13]
- RCTs for food may require shifting of participants' complete diet plan to study the effect of anyone dietary component. This can complicate the result assessment as it will be difficult to confirm whether the observed outcome is due to addition or removal of a dietary component or altogether because of change in the diet plan[13]
- It is difficult to assess the effect of a novel food on the health status of a participant for a longer duration as including a drug in daily routine for longer duration is much easier than changing a participants' diet pattern or convincing them for compliance to one diet plan for a longer period of time[13]
- Conductance of RCTs requires inclusion of homogeneous study population/participants, however, laying down the guidelines for general public health require generalizability in countries like India where the population is a mix of diverse cultural and regional differences in food habits.[13]
Safety concerns
- Form and dose as well as processing of a particular food can affect its bioavailability. Furthermore, other dietary constituents that compromise an individual's daily meal habits can affect the absorption of compounds found in novel foods that have been claimed to have beneficial health effects[13]
- It is difficult to assess acute versus chronic exposure effects of novel foods due to shorter duration of RCTs as well as difficulty in complying with a particular diet plan for longer duration of time[13]
- In case of novel foods with claims to have beneficial impact in case of chronic diseases, assessment can be challenging because of shorter duration of intervention being given in the RCTs as chronic diseases can have longer latency period before the symptoms actually start progressing.[13]
Ethical concerns
- RCTs require control groups in order to understand the normal physiological effects of the novel food component under investigation. However, in order to have such a group, depletion of a nutrient, even to a point of biochemical impairment that might not have an observable clinical or physiological consequence, is ethically unacceptable[13]
- The problem of the control group can be dissolved with a study design that involves only deficient participants/population at baseline as the study population, solely based on their own dietary preferences. However, once a participant/individual has been identified as deficient, it is ethically unjustified to withhold a nutrient from the concerned study participant/individual as would be required for the placebo group.[13]
| » How Can the Challenges Be Dealt with? – Key Considerations | | |
Even though conducting clinical trials for food can seem to be difficult at the current moment due to lack of clear guidelines for their conductance, there are a few considerations, that if made, can ensure a successful clinical trial. Like any other trial, food trials have certain check-points where contemplating on required parameters can ensure the success rate of a food trial as depicted in [Figure 1]. | Figure 1: The figure depicting various time frames at which considerations need to be made to ensure the success of a food trial
Click here to view |
While assessing the food/nutrient of interest
- Will it be palatable or appealing to the population being studied?
- In case of long-duration studies, is the nutrient component tolerable and appealing enough for the study participants to ensure compliance?
- What are the factors that can have impact on the bioavailability of the nutrient compound being studied?
- Can a suitable placebo be selected for blinding purposes against the food being reviewed?
While designing the study protocol for a food trial
- Is the study aimed at producing results that reveal generalized effect on the population residing in a particular area or the aim is to observe effect on the health of individuals belonging to a particular deficiency group?
- Which study design would be best suited to assess the effect of the nutrient compound on the included population without compromising the health and safety of any of the individuals involved?
While data collection and analysis
- Have suitable parameters or outcome measures been selected that can clearly validate the effect of nutrient component being assessed? For example, the Healthy Eating Index is used to assess the nutrient adequacy and diet quality in studies for food; however, since the estimation is based on the self-reported data from the subjects, it is highly likely to observe underreporting or overestimation of a person's nutrient adequacy.[14] Therefore, suitable biochemical indicators need to be included.
| » The Current Status of India in Terms of Novel Foods and Foods with Medicinal Value | | |
As per the section 22 under the Food Safety and Standards Act, 2006, proprietary and novel food means “an article of food for which standards have not been specified but is not unsafe, provided that such food does not contain any of the foods and ingredients prohibited under this Act and regulations made thereunder.”[15] However, this Act did not define “food for special medical purposes” or FSMPs, which was later included in the Food Safety and Standards (Health supplements, Nutraceuticals, Food for special dietary use, Food for special medical purpose, Functional food and Novel food) Regulations, 2016, as “food intended either for particular dietary use specially processed or formulated, or the dietary management of persons and to be used only under medical advice.”[6]
Even though defined guidelines for review and approval of novel foods and foods with medicinal purpose are yet to be laid down, the FSSAI has approval process for such foods. As per the subsection 7 under section 4 of the Food Safety and Standards (Health Supplements, Nutraceuticals, Food for special dietary use, Food for special medical purpose, Functional food and Novel food) Regulations, 2016, the health claims for any article of food require review of adequate documents and quality data (preclinical and clinical) generated as per claim and/or indication for the same by the Food Authority.[6] In case any scientific support is not available, approval by the Food Authority would be based on available scientific evidence.[6] However, there are no defined guidelines for how to go about with clinical studies for such foods in Indian scenario, considering the heterogeneous nature of population residing in the Indian subcontinent. Furthermore, in case a clinical trial is required for a novel food due to the possibility of it posing a specific hazard to the population or a vulnerable group, the scientific committees of FSSAI decide on the clinical trial to be conducted on case-to-case basis as per the Indian Council of Medical Research guidelines for conductance of such trials.[16]
| » Conclusion | | |
Most of the developing countries are streamlining their efforts to define novel foods and FSMPs as well as lay down guidelines for review and approval of such foods for general public due to a mix of regionally and culturally diverse set individuals comprising the general population. Many safety and ethical concerns also emerge while formulating guidelines for designing of studies for food trials. However, due to the ever-increasing rise in the industry for novel foods and growing inclination and/or curiosity of general public toward such foods, need to validate suitable scientific evidences for the claims/indications being made for such foods cannot be neglected. Understanding the taste and/or diet preferences of the population being studied in a trial as well as cautious evaluation and assessment at each step of a trial can help to ensure the success of a food trial as well as aid in formulating suitable guidelines for consumption of a particular novel food or FSMPs by a heterogeneous population.
| » References | | |
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| 6. | FSSAI. Corrigenda for Food Safety and Standards Authority of India, Food Safety and Standards (Health Supplements, Nutraceuticals, Food for Special Dietary Use, Food for Special Medical Purpose, Functional Food and Novel Food) First Amendment Regulations; 2021. Available from: https://www.fssai.gov.in/notifications.php?pages=4. [Last accessed on 2023 Jul 14].  |
| 7. | FSSAI. Frequently Asked Questions (FAQs) on the Food Safety and Standards (Health Supplements, Nutraceuticals, Food for Special Dietary Use, Food for Special Medical Purpose, Functional Food and Novel Food) Regulations; 2016. Available from: https://www.fssai.gov.in/cms/standardsfaq.php. [Last accessed on 2023 Jul 17]. |
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| 9. | Johnston BC, Seivenpiper JL, Vernooij RW, de Souza RJ, Jenkins DJ, Zeraatkar D, et al. The philosophy of evidence-based principles and practice in nutrition. Mayo Clin Proc Innov Qual Outcomes 2019;3:189-99. |
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| 13. | Weaver CM, Miller JW. Challenges in conducting clinical nutrition research. Nutr Rev 2017;75:491-9. |
| 14. | Subar AF, Freedman LS, Tooze JA, Kirkpatrick SI, Boushey C, Neuhouser ML, et al. Addressing current criticism regarding the value of self-report dietary data. J Nutr 2015;145:2639-45. |
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[Figure 1]
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