Clinical trials are scientific studies that focus on improving knowledge of diseases, preventing diseases, and developing diagnostic methods and new treatments or medical devices to ensure better patient care. Researchers are always trying to find effective, preventive, or curative treatments that have fewer side effects or better efficacy. These have already been thoroughly tested in the laboratory or using suitable animal models before they are tested on human participants.
Clinical trials may attempt to study:
Every study may not result in improved care for patients. Some studies may also result in deciding that a new drug does not work or is worse than existing treatments. However, this negative result also helps researchers and clinicians to explore why this is seen and ultimately adds to the knowledge of cancer care.
There are broadly two main types of clinical trials.
Observational studies explore groups of patients of different types (based on diagnosis, treatment, or other characteristics) to understand how differently they behave. Researchers of such studies will not influence any situations that the patients experience but only observe these differences to understand their impact. This way of exploring relationships between groups does not conclude that one caused the other but provides an indication of their association. Observational studies broadly have the following three study designs:
Cohort studies classify individuals based on certain characteristics and follow them to understand who will develop cancer. Then this data is analyzed to understand whether people who develop cancer also have similar characteristics. These types of studies are very useful for understanding risk factors.
Case-control studies are the opposite, wherein individuals with and without cancer are selected into two groups, and attributes about them are explored for differences. These types of studies can provide results much faster, but the conclusions might be less reliable.
Cross-sectional studies select individuals who have developed cancer after being exposed to a certain situation and try to understand if there is a link between these two situations.
Interventional Studies are designs that attempt to understand the impact of a specific intervention by putting patients in very controlled environments such that the effects observed are attributed to the specific intervention to be studied. Interventional studies can have the following study designs:
Pilot studies are done to understand if the main study can be done. They provide proof of concept and help understand the logistical, financial, and time implications of completing the main study.
Prevention trials involve people from the general population or those who might be at higher risk of developing cancer and test different ways to prevent cancer from developing.
Screening trials are studies that help to detect cancer early and are similar to prevention trials in their selection of subjects for the studies. They help to determine if there are newer ways to detect or diagnose cancer.
Treatment trials are the most common studies to explore if there are newer, safer, and more effective ways to treat cancer. There are phases to these trials, and early-phase trials establish if a treatment modality is safe and effective. The later phases focus on whether they are better than placebo (dummy treatments) or existing available drugs that are used for the same type of cancer. Patients are randomly assigned to test or control groups to understand the impact of the study drug.
Multi-arm multi-stage (MAMS) trials are becoming popular, wherein there are several arms of the study to understand how patients in each arm fare compared to a common control arm. The experimental arms keep adding based on what treatment the patients are assigned to. Such trials are usually planned between multiple hospitals and last for many years to be able to understand the long-term benefits of different treatments that are being tested.
Treatment studies are often called clinical trials or medical trials, and new treatments being tested need to complete different phases of clinical trials to be introduced to the market. There are 3 main phases of clinical trials, numbered from Phase 1 to Phase 3, but at times, Phases 0 to 4 may also be undertaken to license the new treatment being tested. If the treatment is successful in the first phase, it will be pushed to the next phase for more tests and, accordingly, to further phases.
All clinical trials and phases associated with them aim to reduce the bias in the results obtained and undertake randomization. This process occurs when patients are assigned to the study groups at random. When the patient allocation happens by chance, it allows the researcher to not have an influence on which patients receive which treatment modality, thereby not being able to influence the outcome of the study.
Another way to avoid bias is by blinding/masking. Blinding or masking is a process of hiding information about whether a patient is getting the treatment being tested or the placebo or standard treatment from the patient, doctor, and other study personnel.
These procedures, when incorporated into the study, help to generate reliable results to determine whether the new drug, combination, or treatment method is safe and effective.
The following are the 5 phases of clinical trials:
Phase 0 trials involve a very small number of people and are focused on determining if the drug behaves the same way as it did in the laboratory or during animal testing. If you are part of such a study, often the researchers are exploring if the drug reaches the cancer cells, what happens to the drugs in the body, or how cancer cells respond to the drugs. This might require you to provide extra blood samples or biopsies to help researchers understand what is happening.
Phase 1 studies are conducted to determine a safe dose for a new cancer drug and assess its toxicity levels. During this phase, new drugs are administered at very low doses, and the patient is monitored closely to observe for any side effects. If negligible, the next group is administered with a slightly higher dose. This will go on until the researchers find a safe dose to work with.
Phase 2 clinical trials are conducted to understand how well the new drug/treatment works.
Phase 3 trials are conducted to compare the new drug or treatment with the existing standard of treatment for its safety and efficacy.
Phase 4 trials are conducted to analyze the long-term safety and effectiveness of a new drug or new treatment and to check if it has any adverse effects that were not apparent during the initial phases of clinical trials.
Below is brief information on the intent, subject population, and duration of each phase:
| Phase | Number of Subjects | The Focus of the Trial | Randomized |
|---|---|---|---|
| 0 | 10-20 people | Checking for harmfulness at low doses. | No |
| 1 | 20-50 people | Dose determination and assessing side effects and physiological changes | No |
| 2 | 50-100 | Looking for how well the treatment works while also assessing the level of side effects. | Sometimes |
| 3 | 100-1000 | Comparing the new treatment to the standard or dummy treatment to check if the new drug is better in any way | Usually |
| 4 | >500 | Understanding long-term effects of drug use. | No |
All medical advances have happened as a result of clinical trials. Clinical trials attempt to find novel ways to prevent, detect, or treat cancer and can include new drugs, drug combinations, or surgical or medical devices. Sometimes they could also be a new way of using existing treatments.
People participating in a trial are invariably exposing themselves to the possibility that these new methods might not work and thus greater care is taken to monitor patients enrolled in trials for any ill effects of the new therapies. Also, most of these new methods undergo testing in the laboratory and on animals before they are allowed to be tested on humans, which reduces the risk of serious adversity.
People may participate in clinical trials for a number of reasons. One of these reasons may be purely for the advancement of science, but for participants with illnesses, it is often a chance to avail themselves of the newest treatments or drugs.
Invariably, all trials are voluntary, and patients should be able to withdraw from the trial at any time in case of any sort of inconvenience. Also, even if there seems to be no apparent benefit from participating in a trial, the knowledge gained from each trial, whether the results are favorable or not, informs the larger population and hence helps in the advancement of medical practice.
In summary, participating in clinical trials benefits patients in the following ways:
Usually, your physician needs to refer you to a trial, and it is always good to ask if there is a trial that is suitable for you. Your specialist would know about any locally available trials or larger national-level trials that may be ongoing and would provide the necessary information and details about them. He would also be able to assess your fitness and ability to take part in the trial based on the entry conditions and determine your suitability to join the trial.
This website consists of a searchable database of all trials being conducted at HCG hospitals. You could search this list based on several search criteria and reach out to the respective doctor or trial contact person to understand your suitability to enter the trial. All the information needed is written in non-technical language that is easy to understand.
Alternatively, there are public databases where you can try to find suitable trials. It is mandatory to register with the Clinical Trial Registry of India, which is maintained by the Government of India. You can search for trials that are being conducted in India on their website.
The clinical trial that you will be a part of should be thoroughly explained to you before you consent to take part in it.
This should include information about:
All the information about the trial will be part of the patient information booklet and should be given to you before you decide to participate. One of the trial teams should ideally be able to walk you through the information in this booklet and answer any questions that you may have.
Since the new treatment is being tested, the research team might not have all the information before the study, relating to how you will feel upon receiving the treatment. But it is their responsibility to inform you about all known side effects and what care will be provided if you experience any of them.
Providing your agreement to participate is a critical step in the research process, and you will be given a document to sign. Ensure that you are comfortable and not being coerced in any way and that all your questions have been answered to your satisfaction, before signing the consent form. Your participation in the trial is entirely voluntary, and you are free to withdraw your consent at any time. This will not affect your treatment, and you should be able to continue standard treatment for your diagnosis.