What are clinical trials?

The long and hard road of laboratory research

It is estimated that there is a lapse close to ten years since a drug starts to be researched until it becomes a treatment approved by sanitary authorities Only five out of every five thousand substances evaluated on the preclinical phases reaches the human experimentation stage; and of those, only one finally gets to enter the market. The need of financing the entire research process with just a handful of labels is one of the reasons for the high price of anticancer medications.

The first step of this ladder is basic research. Through trials using tissue samples, cell cultures and animals, researchers try to prove that the compound has some sort of antitumor activity, and also to find out its behavior amongst malignant cells, which are its mechanisms of action and possible side effects. Animal trials also help to get an idea of the future ideal human dosage and to prove that the substance is not toxic and does not produce malformations.

If during these first studies no security or severe toxicity problems are detected, then the company that owns the patent is able to ask the sanitary authorities for permission to start trials in humans. In order to reach this stage. the trial developer (that could also be a university, a hospital, or a group similar to GEIS), must provide all the gathered information during the preclinical phase and all the data about the research that is planning to accomplish.

The three stages of clinical trials

The objective of these studies is to prove that a new medication is safe, efficient and beneficial when compared to the best treatment to date.  Medical studies in humans employ the clinical trial method divided into three different stages. Only the trials that pass the first stage reach the second; and only those that achieve the objectives proposed on the second stage reach the third. Finally, only the success of the third phase of the trial opens the gates to the commercialization of the researched compound as a true and tested medication.

On the first phase, a trial has the goal to check the safety of a drug, so it is tested on very few participants, usually a couple of dozens, and strictly monitored. With other diseases, the products are usually administered also to healthy subjects, but with oncology treatments this stage is restricted to patients in advanced stages that can get benefits from it and that have consented to try the new alternative. The trials usually begin with a small dose of the drug applied to no more than three people. Only when their reaction has been observed for several weeks, enough to prove that the dosage is safe, the amount of voluntaries in the group is increased. This process is repeated until a level of dosage with the best balance between activity and side effects is determined.

Once it has been proven that the drug does not produce serious adverse reactions, the second phase will determine the compound activity on different situations, while at the same time the studies on toxicity and dosage continue. These trials usually include around a hundred of patients.

The last step of the clinical research is  the third phase with the objective of proving that the new treatment is not just efficient, but if it is better, equal or worse than the current treatments.. At this stage, the number of participants reaches several thousands, and it is needed to make great cooperation efforts amongst dozens of hospitals, usually located in different countries. In the design a control group is already included, which means that the new treatment is compared with the standard therapy considered best up to date. In the case where there is no current standard treatment for the situation at hand, a placebo is used as control. A placebo is an inactive substance that represents the absence of treatment. To apply it, researchers resort to randomization, a fundamental concept in clinical trials.

Randomization

The only way of knowing if a new drug is better than the currently used one is to treat two different groups of patients in parallel and evaluate how many improve their condition on each group. But for this approach to work it is required that the groups are identical in every sense except in the treatment administered to them. In other words, they must have the same distribution by gender, age, cancer development stage, familiar records, or smoking habits, to quote a few.

And this uniform distribution can only be achieved by sheer random. A computer software allocates each participant either to the group receiving the control treatment, or to the one taking the new one, before knowing if it positively contributes in any way. In a simpler way, whatever the allocation is, any participant in a clinical trial has the same chances of receiving the best treatment possible at the end.

Participation in a clinical trial is completely voluntary. It is enough for any patient to refuse to be switched to standard therapy, even though his participation on the trial had already started, as the law protects his right to abandon the study and receive the older treatment..

If the new product fulfills all the objectives, the company in charge is able to ask for approval. The agencies in charge of approval are the regulatory agencies of the drug market and sanitary products: the Food and Drug Administration (FDA) in the USA and the European Medicines Agency (EMA) for EU country members. Both have different criteria and approval stages, so it is not uncommon that a treatment already approved on one side of the Atlantic takes longer to reach the market on the other continent.

Is it dangerous to participate in a clinical trial?

It depends on the kind of clinical trial, as some might be more dangerous than others. To know in depth about the risks of a particular clinical trial, the doctor provides an Information Sheet to the patient with all the details about the possible dangers of participating. Also, the medical team will be able to clearly explain the patient any doubts that could appear.

Side effects related to medication used on a clinical trial are thoroughly examined and the information is sent to all medical participants so they are familiar with the case in particular and avoid it happening to someone else. Besides, the information always has to reach sanitary authorities.

Participation in clinical trials is completely voluntary. It is explicitly forbidden by law to pay participants in Exchange for their participation in a trial.

If a patient accepts to join a study, a written letter of consent is required, by both the patient and the doctor in charge. The patient keeps a copy of this letter with all the details of the treatment that will be received. Another copy remains in the medical center. The patient might not only either accept or refuse to participate in the trial, but has also the right protected by law to abandon or quit the trial at any time he desires, without further explanation or notice, with the reassurance that he will be given the same treatment he would had received if he had refused to participate from the start.

On the other hand, any clinical trial that carries any degree of risk has an insurance policy and must fulfill rigorously with both the Spanish and European laws regarding scientific and medical studies..

When a cancer is not easily treated, a very good option is to participate in a clinical trial. These give patients the chance to get the most recent and advanced drugs and treatments before they reach the market. When speaking of this particular condition, waiting time is usually a commodity they do not have in spades.

Clinical trials are controlled and audited by law

Clinical trials are closely supervised. There is no way that a doctor or a hospital just out of the blue starts trying a new developed drug on human patients. In Europe, the organization in charge of approving new clinical trials, supervise their development and take care of the security of the subjects, is the European Medicines Agency (EMA). Also, in Spain, any clinical trial must be previously authorized by the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) and approved by the Ethical Committee of Clinical research (CEIC, by its Spanish acronym). On these committees not only hospital doctors and pharmacists participate, but also social agents, usually represented by the legal counselors of patient organizations.

It is compulsory that all essays are covered by civil liability insurance. Of course, all treatments, diagnosis tests, surgery procedures, hospital check-ins and further treatment due to complications involved in a clinical trial are completely free, regardless of the fact that the study takes place in a public or private hospital. 

Clinical trials can be supervised through their entire development by Spanish and/or European authorities, so both the procedures are closely inspected and the patients’ wellbeing is guaranteed.

GEIS clinical trials

GEIS has carried out more than 20 clinical trials and has currently more than 10 active ones. Some of them have been designed and promoted by researchers actively collaborating with GEIS. Others are participations in great cooperative trials with continental or worldwide reach. Our trials are developed in both private and public hospitals across Spain and also in foreign centers when other countries are involved.

Unfortunately, there are countless different situations for sarcoma patients, so it is impossible to guarantee the existence of the perfect or proper trial at the time, or one that takes place in a medical center close to the residence of the patient.

On the other hand, it is not enough to want to join a clinical trial. All of them have a criteria list for inclusion into the study, and also another of exclusion criteria that would forbid the participation of a given patient. To be able to be included in a specific trial, it is indispensable to fulfill all inclusion criteria and not be included in any exclusion criteria. If you or a relative that suffers from sarcoma is looking to join a clinical trial, start by taking a look to the Open Clinical Trials section. If you are able to see there a trial that describes a situation similar to yours, please contact us. We will do everything in our hands to locate a sarcoma specialist close to your place of residence that participates in the clinical trial you are interested in.