Clinical trial Q and A for cancer patients, their families and friends
Clinical trials are vital for new cancer treatments
Clinical trials in humans form the final part of a testing process, which lasts years and through which all new medical treatments must pass. Some cancer patients may be invited by their physicians to enter such a trial. Others will independently take the initiative to research the subject and then ask their physician about what possibilities exist.
This hub looks at the background to taking part in tests of new cancer treatments and what is involved. The decision to participate in a clinical study is personal and needs to be made after much thought and discussion. If you are or someone close to you is facing this decision, I hope that what is written here will help.
Cancer drug trials: how they are organized
Every new medicine and medical device has to receive approval from the regulatory authorities of the countries where it will be sold. In the United States, for example, the Food and Drug Authority (FDA) is responsible for issuing such approval. Applying for approval is a complex process, which includes submission of a huge file containing highly detailed information about the product.
Much of this information comes from clinical trials. Trials are conducted in a number of phases as shown in the table.
Types of clinical studies; explanation of phases
Computer models, cell and tissue cultures, microorganisms, animals given a wide range of doses
Collection of data to predict how the substance might act in the body, whether it might be effective in treating a disease, whether and what sort of toxic effects might occur, initial data on potential doses.
Small groups, usually of healthy human volunteers, who are given low doses, which may be increased gradually
How the substance is distributed and processed in the human body (pharmacokinetics/pharmacodynamics). At what dose does it start to cause undesirable side effects, and at what dose do these become unacceptably severe (tolerance/safety).
Larger groups of human volunteers and/or patients with the disease/s the substance is eventually intended to treat. May include comparison with a placebo (inactive substance)
Demonstration that the substance has biological effects in humans that may be therapeutically relevant (efficacy). At what dose does it start to have any noticeable effect. How many subjects respond. Further collection of data on tolerance/safety.
Large groups of patients given therapeutic doses. Usually the substance is compared with a placebo, sometimes also with an already established treatment. These studies can last several years.
To obtain real proof that the substance shows efficacy in treating a disease, preventing complications, relieving symptoms and/or improving survival and quality of life. To see whether it is better than existing treatments in terms of efficacy and/or tolerance/safety. Further collection of data on tolerance/safety.
Also called postmarketing surveillance and conducted after the product has obtained approval and been placed on the market. Mainly based on notifications from physicians and pharmacists.
Collection of data on tolerance/safety over long periods of use in routine clinical practice. Analysis of effects in different patient populations (e.g. age, ethnicity, gender). Cost effectiveness studies.
To read more about cancer clinical trials
A clear and detailed guide written for cancer patients who are thinking about joining a clinical trial. Covers all aspects, such as the questions to ask, the decision-making process and practical issues to address.
What are randomized, double-blind, placebo-controlled (and comparator-controlled) studies?
This design is commonly used in phase III trials. The new experimental treatment is compared to an inactive substance (placebo-controlled) and sometimes to an established treatment (comparator-controlled) that is already used in routine practice. This is to see whether the new substance shows any advantages, such as:
- being more effective;
- causing fewer side effects;
- being more convenient (e.g. tablets taken at home instead of infusions given in hospital).
In such a study, you will be assigned by lottery (randomized) to one of the treatment groups. With a double-blind design, neither you nor the investigator knows which treatment you are receiving. The blinding will last throughout the trial unless it is necessary for the investigator to find out that information, for example in an emergency.
What is expected of a participant?
If you want to participate in a clinical study, you will first have to pass through screening to see if you meet the criteria.
Every study has a list of inclusion criteria. These are conditions you must satisfy in order to be accepted. They could include, for example, age, the stage your cancer has reached, types of previous treatment.
Likewise, there are exclusion criteria, which will prevent you from taking part. Being or intending to be pregnant is an exclusion criterion for the vast majority of studies. Some cancer drug studies are limited to newly diagnosed patients and exclude patients who have already received any form of treatment for their cancer.
Next, you will be asked to sign an Informed Consent Form. By doing this, you state that you have received and understood detailed information about the study and that you are willing to participate.
Once the form is signed, any tests or procedures needed to check your eligibility further will be performed. If these are in order, you will start the study treatment.
You will be obliged to follow all instructions given to you by the study team, take the treatment exactly as prescribed, attend all scheduled study visits and subject yourself to the necessary tests and procedures. If not, you may be withdrawn from the study.
One thing that you are not obliged to do is to continue to the end of the study. Your initial decision to take part is completely your own. Even after having made that decision, you remain free to leave the study at any time without giving a reason. For your safety, you will then be probably asked to attend for one final visit.
Are clinical trials risky?
There are always some risks associated with being in a clinical study.
The new product being tested in a clinical trial is still in an experimental stage so there will be some gaps in the information known about it. It will have only been tested in very small groups previously. This means that, despite all efforts and precautions to minimize risk, some rarer side effects might not yet have been identified and might occur for the first time.
These new side effects could be unpleasant or have serious consequences, possibly even being fatal. Cancer treatments are frequently very aggressive, so the risk of serious side effects may be greater than otherwise.
There is also the possibility that the new treatment may be less effective than established ones. In such a case, the cancer may progress more rapidly than if another treatment had been given.
Some of the extra tests and procedures needed just for the purpose of the trial may carry their own risks. For example, giving blood samples is associated with a slight risk of infection. Thus, the more samples that need to be collected, the greater the accumulated risk. Many cancer patients have a compromised immune system, so the consequences of infection are more serious.
Finally, in a blinded, controlled study, there is no guarantee that the study treatment you receive will be the new productand not inactive placebo. Again, this could affect the rate of cancer progression.
So if there are risks, should cancer patients consider clinical trials?
As well as potential risks, a cancer drug trial may potentially bring benefits.
The best benefit of all, and surely the most wished for, is that the new treatment will have a really noticeable impact on the cancer and prolong life significantly. Better relief of symptoms and improved quality of life in the time remaining are lesser, but also important benefit.
However, there is absolutely no guarantee that either of these results will happen. In particular, in a placebo-controlled trial you might not even receive an active study treatment.
Study participants are monitored extremely carefully throughout. This means that other health problems, not necessarily connected with the study, may be detected and treated earlier than might otherwise be the case.
Many people taking part in clinical studies derive meaning and comfort from the fact that they are playing a vital part in medical research. Even if they get no personal benefits, they know that they are contributing towards the development of better treatments for the disease in future.
In the videos below, Ray and Louisa talk about being participants in clinical trials at Stanford Cancer Institute.
Patient’s own medical insurance
Before making a decision to take part in a study, it is very important to check with your insurer whether participation will impact on your own medical insurance. From the start of 2014, the US Affordable Care Act has made it a legal requirement that all new health insurance plans taken out must cover the costs of routine care of patients participating in clinical trials.However, not all insurance plans taken out before this time provide even this minimum level of coverage to trial participants.
Does it cost to be a study subject, or do they get paid?
Healthy volunteers, who take part in phase I and phase II studies are paid, often generously, for their time and participation.
It is a fundamental rule, however, that patients must not receive any payment whatsoever for being in a study. The reason for this is that a patient must not be swayed by any concerns other than medical ones when deciding whether to take part.
Being in a clinical trial means you do get the study medication free of charge and any extra tests or consultations that are needed specifically for study purposes are paid for by the pharmaceutical company that is responsible for developing the test product (study sponsor).
In addition, the study sponsor is obliged to take out insurance to cover treatment for any injuries or other medical problems you may experience as a direct result of study participation.
The study sponsor generally also reimburses participants for necessary and reasonable costs incurred for travel, food and accommodation while attending study visits.
Would you consider taking part in a clinical trial as a patient?
Who approves and supervises the conduct of clinical trials?
Every study has to get approval from the national regulatory authority (e.g. the US FDA).
In addition, at each site where the study will run, a positive opinion has to be obtained from a local group. This is called the Institutional Review Board (IRB) in the USA, while in Europe it is generally known as the Ethics Committee (EC). Members of the IRB/EC include physicians from various disciplines, as well as nurses, pharmacists, lawyers, moral philosophers/ethicists, scientists and representatives of the general public.
Both the national authority and the IRB/EC review the initial proposal and receive regular reports and notifications during the course of the study. Both have the power to require changes to be made, or even to stop a trial if they consider it is exposing participants to too great a risk or if they find fault with the methodology.
Decision-making should not be rushed
Clinical trials: making a decision
You will never be forced or rushed into making a decision about whether to join a trial. Together with the Informed Consent Form, you will be given a detailed verbal and written description of the trial, its aims, potential risks and potential benefits.
You will be encouraged to discuss the matter with the study investigator, your own doctor and your family and close friends. You have the right to take as much time as you need to make your decision.
You need to think about how being in the trial will affect you. This includes not just the issues described above, but other factors too. In particular, how will attending for the extra visits, tests and procedures required by the study impact on your life? Will you find it difficult to comply with the other instructions and conditions?
Increasingly, trials now include a secondary so-called pharmacogenomic study. For this, you will be asked to donate extra samples of blood or tissue from which DNA will be extracted and analysed. The aim of these studies is to find more about the genetic basis of your disease and how it might be affected by the study treatment. A second consent form has to be signed for these studies. You have the right to refuse this study and still continue to take part in the main study.
For clinical trials in general
For information on all types of clinical trials, not just cancer-related, occurring around the world, the best place to start is the ClinicalTrials.gov web site established by the US National Institutes of Health, which provides patients, their family members, and the public with easy and free access to information on clinical studies for a wide range of diseases and conditions.
How to find a cancer clinical trial
There is no guarantee that your doctor will refer you to a trial of his or her own accord. One survey found that only 2-4% of patients recently diagnosed with cancer took part in clinical trials. One of the reasons for this very low proportion is an equally low proportion of physicians referring their patients for trials.
For this reason, some cancer patients decide to be proactive and find information on trials by themselves.
The National Cancer Institute at the US National Institutes of Health maintains a free public online database of cancer-related clinical trials around the world. Extensive help is available for database users, including a written manual, video guide, toll-free telephone help line and online chat facility.
Having all the necessary information together in a single book may be useful. This book has received only 5-star reviews from readers.