Guinea pig: Do participants in clinical trials risk
We talk a lot about evidence-based medicine.based on the results of clinical studies - but few understand how these studies are conducted and what they mean for the participants themselves. One seems to be a futuristic laboratory with a lot of sensors, another seems that the research is unethical or dangerous, because you can get a placebo instead of a cure for cancer. We describe what mechanisms protect patients of clinical trials and why people go to participate in them.
Who does research and why
Large-scale drug studies are most often conducted by pharmaceutical companies that create them — this is necessary, because without studying the efficacy and safety, no one will allow us to register a drug. From the moment of the creation of a new molecule to the successful registration, it takes about fifteen years, and at various stages tens of thousands of other substances are eliminated, which will not become drugs. After long work in the laboratory, preclinical studies begin - on animals and in vitro, for example, on cell cultures. The standard set is the study of toxicity, effects on various organs and tissues, effects on fertility, teratogenicity, carcinogenicity, and other parameters. Finally, after collecting enough data, the company begins to conduct clinical studies, that is, to study how a potential drug works in the human body.
This is an exciting moment for the pharmaceutical company: you can rely on theoretical data as much as you like, but no one knows how the human body will react to the introduction of a new substance. Clinical studies of the first phase (the earliest, including first-in-human, the very first in humans) are usually conducted with the participation of healthy volunteers. At this stage it is not yet to determine the activity in the treatment of the disease, it is about establishing basic security. The first phase studies are the only ones for which participants are paid. Most often young healthy men are selected for them - and for some of them participation in research becomes an important source of income (we can talk about amounts of 200-300 dollars per day).
The following phases, the second and third, are already close to real life. The third phase of research is aimed at collecting data on the efficacy of the drug, so that it can finally be registered, therefore, patients with specific diseases are involved in it. If we are talking about common diseases like asthma, the number of participants can be in the tens of thousands worldwide. At the same time to participate in the study does not need to be in a special laboratory - it can offer the attending physician in an ordinary clinic or hospital in Russia, studies are conducted in hundreds of medical institutions in different cities.
In 2013, I was diagnosed with breast cancer. We had surgery, then chemotherapy and radiation therapy were ahead. In the oncology center, I was offered to take part in a clinical study of a drug that was developed to reduce the side effects of chemotherapy — that is, so that patients do not vomit, so that they do not have severe fatigue and terrible health. I agreed without hesitation, and not to try a new drug: I simply understood that within the framework of the study, chemotherapy would be of the best quality, with original drugs, and not generics. As a result, the drug itself studied perfectly suited me, the effect was good. I know that it is now registered and sold.
How to achieve ideal conditions
This is hard to believe, but even if the study is conducted in hundreds of clinics around the world, in countries where different languages are spoken and sometimes different standards of treatment and diagnostics are used, all processes, procedures, and registration of data in the study are maximally standardized. For this purpose, the protocol - the main research document - describes the finest details; if it is necessary to measure pressure and pulse after a person has taken the medicine, then the protocol will indicate the exact time of measurement - for example, after one, three or five minutes. All this does not mean that there are no violations - but constant checks can reduce the risk to a minimum, and the analysis of data also takes into account the risk of errors.
In clinical trials, absolutely everything that happens to the patient is recorded - regardless of whether the events seem to be "side effects" of the drug being studied. The cut during shaving can be attributed to the rush, and a fracture when falling on the street - to an unfortunate accident; but if all incidents are recorded, it may become clear that the cuts have become frequent, because the drug causes hand tremors, and the fractures will be associated with increased fragility of the bones.
That was how it was found that sildenafil (a drug that is now used to treat erectile dysfunction) helps to maintain an erection - this drug was developed for the treatment of angina pectoris. The cardiological effects were not very good, but patients so often talked about improving sexual function that it was impossible to ignore this fact. The company took on the development of sildenafil in a completely different profile - and this was a revolution in the pharmaceutical world, when everyone started talking about the industry of "lifestyle drugs." A similar story happened with minoxidil: it was studied in patients with arterial hypertension, when it turned out that it stimulates hair growth; as a result, the drug was registered for the treatment of baldness.
I have been participating in the study of a drug for the treatment of multiple sclerosis for the fourth year. At some point, my usual therapy stopped working, and the choice was this: either to switch to domestic drugs that I do not trust (and which do not differ much from what I received), or to participate in a clinical study of a new generation drug. I trust my doctor, he explained everything well, and I agreed. The effect is very good, my well-being has improved, I am active, I play tennis. I want to continue to stay on this medicine, although it will certainly be very expensive(Pharma companies often give patients the opportunity to continue to receive the medicine after the end of the study until it becomes available, for example, as part of the MHI program. - Ed.).
Ethics and Design
Perhaps the main myths about clinical trials are "the doctor has no idea what the patient is receiving," "you can get a placebo instead of a vital drug," "a person may not even know that they are experiencing something on it." But in reality this is not the case - and if violations occur and do not remain hidden. The key to any research is patient informed consent; usually a person receives a multipage document where the research is described in simple and understandable words, and can easily study it at home, discuss the situation with relatives, and then ask any remaining questions to the doctor. Before the consent form is signed, no research procedures can be conducted.
As for doctors who do not know what the patient is receiving, a double-blind method really means that neither the participants nor the researchers know what kind of therapy is being performed. But at the same time all possible options are known; There may be two or more of them, they may include a placebo, a study drug in different doses, or some already known drugs. It is known in advance what effects and reactions are likely to be expected. There are criteria for which treatment can and should be canceled, and for emergency situations there is an opportunity to find out what exactly was used for a particular participant.
Placebo is not always used: in situations where there is an effective registered therapy, it would be unethical to leave the patient without treatment. If such therapy does not exist, but already at an early stage of the study, it turns out that the new drug is clearly effective, the course of research can change, so that all the participants receive the necessary treatment. Research is also a lot of checks: the quality of the data collected is constantly monitored, the presence or absence of violations, and ethics. If there are any important new data, they are reported to all researchers of the world, notifying at the same time the ethics committees. If changes are made to the study, patients will definitely find out about them, who must again give written consent to further participation (or abandon it). Any participant can leave the study at any time without explaining the reasons.
Benefit and harm
All possible risks are explained to patients in advance - including the risk of unforeseen undesirable reactions that have never been observed before, or complications such as bruising or pain after taking blood from a vein. Each participant must receive insurance that will cover any harm done if it occurs. Money for participation in research does not pay (except for the first phase in healthy volunteers), but they often compensate, for example, the cost of transportation or food while in the clinic.
Sometimes no personal benefit is foreseen for the patient - and they also write about this in the form of informed consent, offering to contribute to science and, possibly, to do useful work for the medicine of the future. Yet the benefits are often obvious, and not only because of the effectiveness of a new drug. Research participants receive increased attention, more regular examinations, blood and urine tests in international laboratories (blood samples from all over Europe, including Russia, may be sent, for example, to Switzerland or Belgium).
Where can I find a suitable study
The main worldwide clinical research database is clinicaltrials.gov, where you can filter your search, including by disease and country names; Research conducted in Russia is also collected on the website clinical-trials.ru. Other options are the sites of large pharmaceutical companies, most of which have Russified pages and the ability to search for clinical research on individual diseases.
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