1 What Is a Clinical Drug Trial?

This is a procedure to evaluate the efficiency and safety of a drug or medical device by monitoring its effects on participants. The research is usually done when a molecule is thought to be useful for treating humans. Thus any trial requires a triad of:

  • The new molecule, or the device.

  • The participants or volunteers.

  • Doctors, research scientists, and coordinators.

A new drug is defined as a medication that has not been previously used in humans to treat a particular disease or has not been given a license to be used for that illness or is in the form of a fixed drug combination containing two or more drugs and has not been approved [1].

2 What Are the Advantages and Disadvantages for a Patient Who Is Enrolled in a Trial?

A trial is undertaken on subjects on a voluntary basis and after an informed consent form has been signed.

The benefits are:

  • The patient gets a new treatment before it is available to the general public.

  • He plays an active role in the health care system.

  • The investigators provide better and more vigilant monitoring with more frequent health check-ups.

  • By participating he/she may be helping other patients with the same illness to get better treatment for their health problems in the future.

  • Access to support groups and resources becomes easier.

The disadvantages are:

  • The new therapy may cause serious adverse effects.

  • It may not work, or it may not be better than the standard of care.

  • The patient can be part of the placebo rather than the treatment group.

  • There can be inconvenience from the frequent medical visits and blood tests.

figure a

3 What Are the Various Stages of a Clinical Trial?

These are the:

  • Preclinical trial

  • Phase 0

  • Phase 1

  • Phase 2

  • Phase 3

  • Phase 4 (Fig. 47.1)

Fig. 47.1
figure 1

Stages of clinical trials

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It has been estimated that it takes approximately 15 years to convert a small molecule in a laboratory into a life-saving drug and finally getting approval to market it [2].

Pre-clinical trial—In this phase drugs are tested in non-human subjects (in vitro and in vivo only), to gather data about their efficacy, toxicity, and pharmacokinetics. During this phase, the dose is unrestricted.

Phase 0—In this phase, a very small sub-therapeutic dose of the drug is tested in a small number (about 10) of subjects to assess for pharmacokinetics, pharmacodynamics, and particularly its bioavailability and half-life in humans.

Phase I—In this phase, a larger number of healthy volunteers (20–100) are administered sub-therapeutic doses but increasing amounts of the drug to assess its therapeutic dose range.

Phase II—In this phase, therapeutic doses of the drug are administered to a larger group of patients (100–300) to assess its efficacy and safety.

Phase III—Usually conducted by both clinical researchers or physicians. In this phase, therapeutic doses of the drug are administered to (300–1000) patients for assessing its efficacy, safety, and side effects.

4 What are Phase IV and Post-marketing Studies (PMS)?

Formerly, there was some vagueness in the definition and requirements for Phase IV and PMS. In 2019, New Rules, have differentiated the requirements for conducting Phase 4 and post-marketing surveillance studies for new drugs (Table 47.1).

Table 47.1 Difference between Phase IV and Post-marketing studies from regulations perspective
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In the New Rules, 2019, Phase IV studies would include investigations related to drug–drug interactions and dose–response or safety studies. In these, the ethical aspects for protection of the rights, safety, and well-being of the trial subjects will be followed as per the regulatory provisions. It also includes compensation for clinical trial-related injury or death and good clinical practice guidelines [3].

Post-marketing Surveillance Studies are conducted with a new drug under approved conditions of its use. The regulatory provisions and guidelines applicable for the clinical trial of a new drug are not applicable when a drug has already been approved for marketing.

5 Is the Real-World Data the Same as Post-marketing Surveillance?

Although both are observational or non-interventional studies each has very different data. When a drug comes into the market it has already undergone a randomized controlled trial under strict conditions but when the drug actually reaches a market in the real world the situation may be very different. This type of study gives more value to already available data and is called real-world data. These studies are longer than the clinical trials and the data is collected by pharmaceutical companies or insurance authorities [4].

6 Is India a Potential Hub for Clinical Trials?

India has all the resources to do clinical trials. The reasons for this, include the large naive population with varied characteristics and multiple ailments, along with numerous high-level tertiary care facilities. Along with this, the cost of trials is lower compared to Western nations, there are high enrolment rates, greater patient agreement, and lower maintenance [5]. Thus these advantages are:

Investigators

  1. (i)

    Many specialists and subspecialists.

  2. (ii)

    The medium of instruction during training is English.

  3. (iii)

    More than 7 lakh English speaking doctors.

  4. (iv)

    Treatment guidelines are as per the western literature.

  5. (v)

    A large number of subjects are compliant.

Patient Population

  1. (i)

    Huge population who are therapy naive.

  2. (ii)

    Large patient pool has acute or chronic diseases.

  3. (iii)

    Many patients have lifestyle-related disease.

  4. (iv)

    Many patients with cancer and HIV/AIDS—both common area for research.

Clinical Research Infrastructure

  1. (i)

    Over 542 training medical institutions.

  2. (ii)

    79,855 medical graduates per year

  3. (iii)

    739,024 hospital beds

  4. (iv)

    60,000 diagnostic laboratories

  5. (v)

    Many scientists and engineering graduates.

  6. (vi)

    Computer savvy biomedical health workers.

  7. (vii)

    Good air/surface transport facilities across country.

IT Support

  1. (i)

    Highly developed.

  2. (ii)

    High-quality digital connectivity.

7 What Is the Status of Clinical Trials in India?

The journey of clinical trials in India has been a roller coaster [3, 5, 6]. The ups and downs are related to the regulatory authorities. Recently the number of trials has been on the rise and this has been described as the ‘golden period’. The new Drugs and Clinical Trials Rules (2019) have promoted clinical research in our country. The data below shows that between 2000 and 2107 [7] India was in the top ten countries in research and innovation (Table 47.2).

Table 47.2 Top 10 countries in clinical research
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8 Should We Be Conducting Clinical Trials in India?

There are many diseases/syndromes, which are still not curable or treatable. Diseases like autoimmune disorders, amyloidosis, various cancers, certain infections caused by antibiotic-resistant organisms still need extensive clinical research and drug trials. A decrease in the ability to conduct these trials due to multiple factors inhibits the growth of science and human progress. There is a need to consolidate efforts to improve awareness about the general safety of clinical trials among both doctors and the lay public. This can be done by:

  1. 1.

    Informing patients with data about the safety of previous trials.

  2. 2.

    Maintaining detailed records and data of patients.

  3. 3.

    Holding awareness programmes among doctors at multiple levels, to convince them about the safety of clinical trials.

Along with these measures, there we need to keep a strict watch on their quality and their ethical standards.