Drug development is an important step that consists and preclinical and clinical development. Preclinical includes toxicology and animal pharmacology studies. Once Preclinical is over, clinical phase starts with phase I, Phase II, Phase III studies and Phase IV studies.  The drug get marketing approval after Phase III studies are over.  The drug development under goes various kind  of challenges like in phase III study  how many patients to be involved, what should be the standard material, study design should be double blind or not, what is the duration of the treatment and what will be total treatment time. To plan and execute a study these points must be sorted out and planned it properly. The data point has its own challenges. These must be cleaned and checked before doing analysis.

Even though the challenges of are huge but the growth of Industry has taken a major step forward. Many Pharmaceutical companies and CRO are getting themselves involved in clinical research Industry. Various disease conditions both old and recent like COVID has forced them to innovate.  Covid has also caused them to innovate new drugs and therapies and many Pharmaceutical companies, Nutraceutical companies, Ayurvedic companies and food companies has come up with various products that can increase disease fighting ability and enhance body/s immunity. Pharmaceutical and Ayurvedic companies fight for diseases where as Nutraceutical companies look for new immunity booster for the body. That means these new products need to undergo drug development process. For pharmaceuticals, we need to do all Manufacturing, Quality control, Quality Assurance, preclinical, and clinical data as per regulations, GMP, GLP and GCP guidelines. On the other hand, the food companies who are focusing on producing immunity boosters they need to do Clinical trials of their food product, especially when product is having health claim.

Covid has increased in demand for pharmaceutical products and food products and so the opportunity in clinical research sector. There will be challenges in the drug development sector and there will be opportunity in the pharmaceuticals sector especially clinical research.

Important points for Sponsors to have meaningful relations with Site

Sponsor can create of positive relationship with site and that from the onset itself. This may include study design decisions and execution decision that reduces operational hiccups, prevent protocol amendments and decreases burden in particular on site. To make efficient trials, sponsor should aim for building good relationships with investigators to collaborate. Although starting and then nurturing Sponsor Site relationship  can be difficult assignment because of  increased competition.

The important points to built meaningful relation with sites could be

• To keep hospital supplies and IP ready so that whenever there is any enrollment it should not be rejected because of hospital supplies and IP
• Training is important part of GCP, It gives to confidence of handling the project as per guidelines. But repeat trainings can be dangerous, so only those who lack in training should be given training on GCP, SOPs, Regulatory guidelines etc.
• One of the important binding between sponsor and PI is distribution of the funds. So, Once you have signed document of financing the research project, then milestone must be match and funds must be released on time to time basis.
• One of the possible causes of good relationship is to have minimum protocol amendments. Any alteration in protocol can be a tedious task so keep it as low as possible.
• Monitoring should be done as it rule out the protocol changes. The best way to do monitoring is to inform in advance of monitoring date and then CRA comes for monitoring. Site close out visit should also be informed and should be done very carefully so that data collected to accurate.
• Data analysis is crucial component of Clinical Trials. Entries must be checked in the software for their accuracy and correctness. Each entry must be correct and statistical analysis should be accurate.

By doing some of the above things sponsor and investigator can have a good relation for clinical trial.

Impact of Covid-19 on clinical trials

COVID-19 has effected all the people of low, middle and high income families including all the races, genders and age. It messed up human lives and impacted hugely on health facilities including clinical trials. Due to the rise in COVID surge, all the focus of the health care system was on finding effective therapeutics and vaccines against COVID while other trials already in the pipeline came to a halt or totally disrupted. Prior to COVID-19 there were many trials on the list to be completed and with the addition of new COVID related trials, the number of studies to be initiated also got added to list of pending trials. The good thing is that the number of trials are growing very fast in India , but challenges to initiate and complete these trials has also increased.

Hindrances faced by clinical trials

COVID-19 has significantly disrupted clinical trials and has resulted in a long pipeline of the trials to be conducted or yet to complete. These include:

• Delay in the initiation of planned trials.
• Temporary suspension of patient recruitment.
• Delay in ethics committee meetings.
• Overall slow recruitment in ongoing trials.
• Extension of the trial duration.
• Overstressed hospitals and resource systems.
• Change of physical visits into virtual visits.
• Prioritizing new test applications to only those that treat diagnose or prevent COVID-19.
• Recruited patients having to leave the clinical trial for any reason.
• Inability of the vendors and contractors to deliver drugs to sites.
• Risk of compromised data if new procedures are diverging from the original one.

Initially maximum trials were disturbed due to the temporary suspension of the recruitment but later the suspended trials were seen to recruit participants as an impact of pandemic decreased during mid-2020. However, trial initiation and recruitments are still at slower pace then the expectations. Hematological disorders and gastrointestinal related trials have faced the highest disturbance due to the COVID-19 relative to the overall recruiting and planned trials followed by oncology and the CNS (central nervous system) diseases trials. The least affected trials were of the infectious disease as due to COVID this area continues to have many trials for vaccines and therapies.

Concerns related to clinical trials due to COVID-19

GlobalData’s extensive surveys showed turbulence in the clinical trial studies and were the concern of the primary business followed by the concern regarding recruited patient’s safety and employees involved in the trial. The concerns got driven by the requirements of social distancing and shortage of the personal protective equipments in the whole world during the initial days.

Among the clinical trial concerns, the inability to start trials or delay in the start was the highest concern, followed by the impact on participants which could be because of impacts on trial sites or the inability of the investigator to enroll participants. The third most crucial concern was the safety of the patients which could be due to perceiving risk of virus spread at trial sites.

Effects of COVID-19 mitigation strategies on clinical trials

Strategies like lockdowns and social distancing resulted into mobility restrictions and stay at home orders. These are very helpful in mitigating the spread of COVID-19 but on the other hand were creating major obstacles for clinical trials. Lockdowns were driven mainly because of the safety concerns of the patients and there was increased concern especially in high risk indications for COVID-19 or indications where patients due to some difficulties were not able to travel.

COVID accelerated Remote technologies in clinical trials

The unprecedented COVID-19 situation has changed the everyday lives of the people and the way clinical trials were conducted. As conventional ways were not possible to perform, innovative technologies accelerated to support the trials to bring safe and effective therapies in the market.

COVID-19 has flourished the idea of remote technologies in clinical trials which now is perceived as a “Silver Lining” to COVID-19. These include telehealth, e-consent, remote data capture and remote randomization. The virtual platforms allow the clinical trials to be conducted remotely which are easy to handle and are very useful in carrying out and monitoring patients without having the fear of spread of COVID or other infections. It also provides greater flexibility to the investigators and may continue to persist past COVID according to the convenience of the patients.

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Research-based health claims help the companies to build the brands, as they are more trusted by the consumers.

Health claims are the declarations made by the companies about their products (such as pharmaceutical products, dietary supplements, herbal products, ayurvedic products, nutraceuticals, etc) on the basis of scientific research.

As consumers play a major role in providing strength to the product, it clearly needs to gain the trust of the consumers. This can be accomplished by generating research evidence and building health claims.

From ingredients of the product to its health benefits, the claim can be made for anything through Clinical Trials.
Besides clinical trials, animal studies (preclinical studies) also help to support the health claim. The claim for a product can be placed under any of the fields given below:

• Functional claims:

This claim is related to the beneficial effect of the product on the normal well-being of the person. But one cannot claim for the treatment of a specific disease. These claims just include the effect of the product on the physiological and psychological health of humans.

i.e, as observed from a clinical trial, specific nutrients of a food product (which have been studied) have the capability to provide growth and energy to a person.

• Therapeutic claims:

These claims include the effect of a particular component of the product (bioactive component) in treating a disease, as proved by a clinical trial. These claims show the direct link between the bioactive component of the product and its therapeutic effect on the body. So, clinical studies providing proof for the therapeutic effect of the product help to openly claim the efficacy/safety of the product in humans to treat a disease.

i.e, one can claim that your anti-diabetic product is highly effective in treating diabetes as it has been proved in a clinical study on diabetic patients.

• Disease risk reduction claims:

It is common these days that unhealthy dietary habits lead to an increase in the risk of a specific disease. But, during a clinical study, if a product has been proved that its components are very healthy to be consumed or they do not increase the risk of diseases, then, it can be claimed openly for the product.

i.e, by doing the clinical study, you can claim that your product is either rich in some nutrients or specific bioactive components which help to lower the risk of a disease or you can also claim that your product is free of some unhealthy components (such as unhealthy fats) that it can help to lower the risk of heart disease. All these kinds of claims are covered under this category of ‘disease risk reduction claims’.

• General health claims:

The products can also be claimed for their consumption in a healthy manner or according to a specific dietary guideline which can be generated by doing clinical trials on that product. Clinical trials help to evaluate these dietary guidelines or patterns to consume the product.

i.e, you can claim that your food supplement will give its maximum effect if it is consumed once, twice, or thrice in a day (depending upon the results of your clinical study).

Validated scientific proofs help to advertise or market their product under any of the claims listed above.
You can advertise your product with a specific claim if you have scientific proof for it. Once you have done the clinical trial for your product, you can claim it, market it, advertise it and you can also label it with the claim.

The research data can be published in National and International Journals of high impact. Claimed products with research articles also attract the attention of the doctors & give them the confidence to prescribe the product. More is the prescription of product more will be the awareness about the product & better accepted it will be by the doctor as well as the end consumer.

Clinical trials are research studies that are performed on human beings, either healthy volunteers or diseased patients. Each clinical trial is done to answer the scientific questions and to find out the better ways to prevent, diagnose or treat a disease, syndrome, or disorder and also to compare a new treatment with that which is already available and is in use. For the successful conduct and completion of a trial, patient recruitment is a critical and challenging step. Without patients, clinical research doesn’t happen. Medical advances depend on their participation. Sometimes due to the following mistakes, patient recruitment gets affected that results in the delay in the completion of the trial, thus also affecting the CRO’s and Sponsors relationship. These mistakes along with steps to correct them are given below:

1. Complex Protocol:

A complex protocol is one of the reasons that participants refuse to participate in the study. Protocol preparation is the first and critical step in the designing and conduct of the clinical trial. If the protocol is too complex then the study won’t apply to a significant portion of the patient population. Complexity in the protocol can cause confusion for study subjects and if people will not understand the protocol, they would not like to participate, no matter how beautifully the things are designed or executed. So the protocol must be simple and should be designed by incorporating the patient’s perspective, to promote enrollment and realistically reach the available population.

2. Incomplete information:

Incomplete information in the recruitment material (ICF (Informed Consent Form), CRF (Case Record Form), etc.) is another cause. If the recruitment material doesn’t reflect the motivations of participants, then people would not like to participate. The person dealing with people or patients should know that why people do and don’t enroll for clinical trials. Recruitment materials should reflect the intent of the study.

3. Research Specifications of Inclusion and exclusion criteria:

A common mistake is the lack of research subject specifications i.e. inclusion and exclusion criteria. These criteria help other researchers to understand that why current results might differ from other published studies. For example specify the gender, parameters to assess for screening, etc. With too many inclusion/exclusion criteria requirements, willing people often are not able to participate because they don’t qualify. So the subject specifications must be clear, needful, and related to the study only.

4. Awareness of clinical trials:

Lack of awareness about clinical trials among the people may be one cause that they don’t participate in the study. If more people know about clinical trials, then there would certainly be more participation. So, it is important to educate the people about the clinical trials through pamphlets, brochures, media, etc. The encouragement from physicians, pharmacists, family, friends, and others can influence the decision of the people to participate.

5. Uncertainty about Patient Safety:

Fear about the outcome of the study may also force the people not to participate in the study. Unknown outcomes, uncertainty if a new treatment can help them, being experimented on, possible side effects, and receiving a placebo instead of an actual treatment are a few common fears of the people. As patient safety is the priority, so by ensuring patient safety, one can motivate the people to participate in a trial.

6. Communication between Participants & CRC:

Lack of communication between the participant and the person dealing with the participant is also one reason. It’s also important for the CRC or PI to be prepared to answer the questions that result from the promotion of study materials. If the person dealing with the subjects (PI (Principal Investigator) or his designee, CRC (Clinical Research Coordinator), etc.) would not be able to answer or clarify the doubts of the people, then they won’t participate in the study. So PI or CRC should have complete knowledge about the trial and should be able to clarify the participants’ doubts. CRC must inform the participant about the follow-up visits and should take the feedback from the participant on each follow-up, about any side effect, if they felt.

Inability to track the results may be one of the biggest mistakes that can be made in patient recruitment. It’s important to ask each participant that how they heard about the study. Sites can use metrics and analytics as hard data to justify why they need an increased advertising budget. So by analyzing what was effective and what didn’t work, helps to plan future recruitment, knowing what to continue doing and what to do to avoid making the same mistakes.

Looking at the need for randomized clinical trials

to ensure the safety and efficacy of new medical products and added indications, FDA released two separate draft guidance that will each help provide clarity for medical product companies, as well as other interested parties, on FDA’s current thinking and recommendations for a few different types of communications about medical products. These draft guidance are:

1. Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and Answers:

This first draft guidance explains the FDA’s current thinking and recommendations on firms’ communication of health care economic information (HCEI) about approved drugs. It also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

Payors include formulary committees, or other similar entities with knowledge and expertise in the area of health care economic analysis that is responsible for making drug selection, formulary management, and/or coverage and reimbursement decisions on a population basis regarding drugs and/or devices for health care organizations, which may include entities such as integrated health care delivery networks, hospitals, and hospital systems.

FDA is aware that payors seek a range of information on the effectiveness, safety, and cost-effectiveness of approved drugs, including information from firms, to help support their drug selection, formulary management, and/or coverage and reimbursement decisions on a population basis.

Because coverage and reimbursement decisions by payors impact a large number of patients, FDA believes it is essential that HCEI provided by firms to payors about their approved drugs be truthful and non-misleading.

2. Medical Product Communications That Are Consistent With the FDA-Required Labeling —
Questions and Answers:

This second draft guidance explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

This draft guidance provides information for manufacturers, packers, and distributors and their representatives (collectively “firms”) of drugs and medical devices for humans, including those that are licensed as biological products, and animal drugs (collectively “medical products”), about how FDA evaluates their medical product communications, including their promotional materials, that present information that is not contained in the FDA-required labeling for the product but that may be consistent with the FDA-required labeling for the product.

FDA determines whether a medical product is safe and effective for use under the conditions prescribed, recommended, or suggested in the proposed labeling submitted to FDA with the product’s marketing application or submission. In making this determination, FDA evaluates whether the conditions of use in the proposed labeling are supported by the required levels and types of evidence of safety and effectiveness and whether the benefits of using the product under those specific conditions of use outweigh the risks of the product.

After FDA approves or clears a medical product, the FDA-required labeling sets forth the conditions of use under which the product has been shown to meet the relevant standard for marketing and it provides directions and information on how to use the product safely and effectively under those conditions.

Even if communication is consistent with the FDA-required labeling, the representations or suggestions made about the product would misbrand the product and could subject firms to enforcement action if the representations or suggestions are false or misleading. Accordingly, the draft guidance both describes the FDA’s thinking on the types of information that are consistent with the FDA-required labeling and provides general recommendations for how this information can be conveyed in a truthful and non-misleading way.

Obesity is one of the most prevalent health problems and new treatment strategies are developing at a very fast pace.  Looking at the market size of anti-obesity products, many anti-obesity agents are developed by Pharmaceutical and Food companies. These products have to undergo pre-clinical & clinical development processes to establish their safety & efficacy for human use.

There are various strategies to treat obesity which include:

• Appetite controlling
• Inhibiting Fat uptake

It becomes all the more important that the study protocol & its outcome must have clarity about the mechanism of the anti-obesity investigational product. Some of the following critical points one should keep in mind while designing its protocol.

• For clinical trials of anti-obesity agents, it becomes all the more important to have standardized protocol and meaningful endpoints.
• There should be clear instructions regarding diet, exercise, and other behavioral regimens.
• Lifestyle modifications are a must for the management of obesity and the clinical study protocol must have details of lifestyle counseling and their compliance during the study period. Lifestyle counseling by dieticians or health educators can add huge value to the study outcome and can benefit the sponsor.
• In obesity trials, the sequence of the food, like protein before fat and carbohydrate or vise-versa can change the outcome of the study and can impact product efficacy in a huge manner.
• Exercise such as walking and cycling extra can be added to the study protocol.
• Frequent follow up with the patient are important for better compliance of the patient. Initially, every two-week follow-up and then once four weeks follow-up is recommended for long-term anti-obesity studies.
• Subjects to be enrolled for initial clinical trials should have a BMI of 30 without co-morbid diseases.
• Subjects with histories of anorexia Nervosa or other extreme eating disorders should be excluded.
• The age range should be as wide as possible.
• Prior use of anti-obesity agents should be documented, and a subject should have been of any anti-obesity drug for at least 6 months.
• Subjects should have had a stable weight with changes of ~3 kg in the last 3 months to 6 months.
• Weight loss should be the primary outcome.
• Cardiovascular risk factors, such as blood pressure, serum glucose, lipids, uric acid, and other measures should be assessed as secondary outcomes.
• Dropouts should be minimized by appropriate strategies built into the protocol.