Clinical Trials

       Cancer is a disease associated with significant complications arising out the disease itself or the treatment(s). These complications can be long ranging and severe and can impact the functioning of the individual in his home, workplace and in the society. In addition despite efforts being made to detect the disease early a large proportion of the patients will ultimately succumb to the effects of the disease especially where they present at an advanced stage. As we all know despite the progress made in treating cancers by various methods a lot of room for improvement exists. Even in cancers which are considered curable by modern treatments e.g. Leukemias, side effects of the intense treatment can continue to affect a person for the rest of the life time. Clinical trials are research projects conducted to test new and potentially better ways of controlling the disease and reducing the complications of the treatment. Clinical trials are the final but most important step prior to application of a drug or a treatment which has proven itself in laboratory or in animal testing models. Majority of the treatments being done for cancer these days are the result of hundreds of such clinical trials done in the past.

The subject of the research for clinical trials may include one or all of the below:

1. To disconver new ways of treatments
2. To test new ways of sequencing existing treatments
3. Methods to prevent or screen for cancers in the population or high risk groups.
4. Effectiveness of treatments to reduce the side-effects and improve the quality of the life.

        Clinical trials are one of best methods available for availing standard and high quality cancer care. These trials are not conducted arbitrarily but only after stringent vetting by a insitute scientific committee and an multidisciplinary ethics committee. Each trial will come with a detailed and standard method of conducting the study which is called a protocol. This protocol includes information on all aspects of the trial for example:

1. What is the need for the trial?
2. Which patients are eligible for inclusion in the trial and how many patients will be treated?
3. How and what treatments will be given as the part of the trial?
4. How will the patients be managed during and after the trial?
5. How will the data be collected, stored, analyzed and presented?
6. What is the expected benefit from this trial?

        Conducting clinical trials is an essential requirement in modern oncology practice as without trials no new treatment can be given to a patient. These trials allow us to understand the exact benefits or risks of a given treatment for a given group of patients. The serial improvement in the survival seen for several cancers like testicular cancers, leukemias, lymphomas and pediatric cancers is the result of decades of well conducted clinical trials. For several cancers it has been shown that patients enrolled in clinical trials tend to have a better survival as compared to those patients who have not been.

Clinical trials may be of several types. The most commong types are:

1. Trials dealing with a treatment form: These trials involve one or more treatments in a given group of patients. The aim of these types of trials is to see if any treatment is better than the standard treatment in terms of cure rates and complications. In addition for any new treatment small scale treatment trials are undertaken to understand what is the benefit and the side effect profile for a given treatment type.
2. Trials dealing with cancer prevention and early detection: These trials study methods to detect cancers early and prevent them from occuring or recurring. Prevention and early detection are the two most effective and cheap methods of cancer control. These trials enroll a large proportion of often healthy patients and are crucial in the progress against cancer.
3. Trials dealing with quality of life and palliative care: These trials deal with the quality of life that patients experience when suffering from cancer or its treatment. In addition palliative care trials are important to understand the overall effectiveness of an intervention in reducing the cancer related complications.

          Clinical trials may be randomized or non randomized. Randomized clinical trials allocate the participants into groups by a random method (akin to a coin toss). These trials aim to discorage and eliminate most forms of bias which may affect the results of the treatment. For example in non randomized studies a greater proportion of patients with a poor health may get treated with a less intensive form of treatment. This in turn can make the results of the less intensive form of treatment inferior to the more intensive treatment. Random allocation aims to remove this important form of bias in treatment selection ensuring that the results obtained can be generalized to all patients. Randomization does not mean that your treatment is being determined by luck. Prior to conducting randomized clinical trials care is taken to ensure that as per the current sciientific knowledge the results of the two treatments being compared are equal in most respects. Thus irrespective of the arm being allocated into you can rest assured that you are getting nothing less than the current standard of care.

Clinical trials may have a description of a phase. These phases indicate what we are aiming to test in the trial. The following are the types of phases:

1. Phase I: This form of clinical trials is for testing a new treatment and assessing the overall toxicity of various dose levels for the given treatment. These are usually conducted in very advanced cancers patients in whom multiple lines of treatment have failed and who have very few or no options for further treatment. Although sometimes good responses can be obtained in these trials, the objective is to assess the side effects of the treatment so that future trials can be designed in order to compare the effects with a well tolerated dose. Any treatment being introduced as a Phase I trial has to be extensively tested in animal and cell culture models in order to establish the safety and effectiveness of the treatment.
    
2. Phase II: These clinical trials look at how effective a new treatment is. These trials may or may not be randomized. When randomized these trials usually have a standard treatment arm in which the current standard of treatment is being given. Phase II clinical trials help to show that a given treatment is indeed effective in the treatment of cancer. In addition additional data regarding the side effects are also obtained.
    
3. Phase III: These are large clinical trials often conducted in multiple cancer centres where large number of patients are treated. Phase III trials are always randomized and test the new treatment method against an established (or standard) treatment method. While the major goal is to look at the effectiveness of the treatment in controlling the cancer side effects, quality of life and cost effectivness are all studied as a part of this form of study. This form of studies enroll the largest number of participants amongst all the three forms.

       Clincial trials while important are NOT binding on the patient. There are several benefits and potential risks that can result from enrolling in clinical trials. The final decision to enroll or not rests on the patient and not on the physician. Some of the expected benefits that can result from the trial are:

1. Patients will be treated with a novel treatment that is not available to general cancer patients.
2. Patients will get closer attention from the research team with more frequent interactions and better control of your symptoms.
3. If the novel treatment has a benefit in terms of cancer survival or less side effects patients have a better quality of life or an increased life span or both.
4. Findings from the study can help other cancer patients in the future.

Some of the risks associated with a clinical trial include:

1. The new treatment may not be more effective or be even less effective than the current standard of treatment or it may have more side effects.
2. You may need to make more frequent visits to the hospital and undertake more tests in order to see the patients' disease status and side effects.
3. Even if the new treatment proves beneficial for the general patient population it may not be effective in the given patient.