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Medicine: from the clinic to the drugstore

Medicine: from the clinic to the drugstore

Advances in medicine and access to better and better drugs is possible thanks to scientific research in the field of biomedicine. Substances are first tested in pre-clinical trials using tissues, computer models and laboratory animals. If the results are promising, drugs enter the clinical trial phase, during which they are tested on human volunteers. It is only upon the completion of this phase that medicine is cleared for sale at drugstores.

Before clinical trials are started, any research team working on a new treatment is required to submit its project to expert evaluation by a bioethical committee, which assesses potential risks and rewards. If the project is accepted, clinical trials can begin to evaluate the safety and effectiveness of the drug.

There are several stages of clinical trials:

  • Stage one is focused mainly on the safety of a drug, though sometimes its effectiveness is also preliminarily tested. The drug is administered to a very limited number of volunteers; in most cases, people with a clean bill of health, though in the case of oncology due to high toxicity of the medicine, it’s mostly patients who have exhausted all other options. This stage is very strictly regulated, as substances are introduced to the human organism for the first time.1
  • During stage two, the same or slightly larger amount of a drug is administered to a more numerous group of volunteers.
  • Stage three is devoted almost entirely to safety and effectiveness of the potential drug in comparison to currently existing forms of treatment. This time, the test is conducted on patients divided into two groups: one of them receives the experimental drug, while the other get either a standard medication or a placebo. These tests are most often ‘double blind’, meaning that neither volunteers nor researchers know which patient is assigned to which group.

Additionally, after the drug is cleared for use, more data is collected during the fourth stage of the trials. It’s important to note that clinical trials frequently last for several years, and as little as 10­­­–15% of tested substances are finally registered as medication.2

How is a clinical trial different from therapy?

The first three stages of clinical trials aim to ascertain whether the tested substance is indeed an effective medicine. Therefore, it’s necessary to make a distinction between clinical trials and therapy (treatment). In the case of treatment, the only goal should be the health of the patient, while clinical trials are conducted to gather reliable scientific data, which will attest to the safety and effectiveness of the drug. This is why every clinical trial needs to be approved by a bioethical committee.

Clinical trials are designed based on therapeutic intentions, i.e. to maximise the probability of successful treatment for the volunteers. For instance, in stage one, most of the participants receive an amount of the tested substance that is as close to the standard therapeutic does as possible.

In stage three, patients might be randomly assigned to the group that receives an already registered drug to compare it with the tested substance. At this stage, research sometimes conduct outcome-adaptive trials: if it turns out that the tested substance has positive effects, it is administered to more patients. During all stages, the core principle is to not endanger the health of the participants.

Patient’s health is top priority

It’s estimated that about 50% of drugs administered to children have never been tested on young patients.3 This means that doctors are prescribing them based solely on the data collected from adults. Meanwhile, some diseases that affect children do not affect adults; additionally, the physiology of a child’s body may change the drug’s effect.

For these reasons, it would be best if doctors had access to data from clinical trials featuring children. This proposition, however, entails several innate problems.

A lot of serious children’s diseases are very rare, which means it’s not easy to convince pharmaceutical companies to fund them. Moreover, children participants require much more protection in comparison to adults. To minimise the risk and maximise potential benefits, additional regulation are enforced. The most important of them: potential drugs can never be tested on children until they have been tested on adults (at least stage one clinical trials).

Clinical trials with children

Even though in the last several decades child mortality caused by cancer has dropped by more than 50%,4 it is still the most prevalent cause of death in children. For that reason, paediatric oncology is in constant search for new drugs. Scientists have been able to gather data on the effectiveness of already registered medication, but don’t have enough information on the risk and rewards (i.e. therapeutic efficiency) in various stages of clinical trials.

The paper Risk and Surrogate Benefit for Pediatric Phase I Trials in Oncology: A Systematic Review with Meta-analysis published in PLOS Medicine aims to shed more light on this matter. It compiles data collected during all stage one clinical trials in paediatric oncology in the years 2004–2015. Its authors, a research team led by Dr hab. Marcin Waligóra from the JU MC Faculty of Pharmacy, have analysed the results of 170 clinical trials featuring 4,604 young patients and compared them to relevant data collected from adult volunteers.

It’s important to remember that stage one volunteers can only be recruited from patients that are in advanced stages of diseases and have exhausted all other options – in essence, they face a choice between palliative care and clinical trials. The risks and rewards of this stage are much different than those of later stages: the more advanced the research, the more likely it is to result in a positive outcome, with a decreased chance of side effects.

According to the researchers’ analyses, despite stricter regulations, the direct risks and rewards in stage one clinical trials in paediatric oncology are comparable to those with adult volunteers.

The results of the research project will prove very helpful in making informed decisions when it comes to entering stage one clinical trials and are important not only for young patients and their parents, but also researchers, pharmaceutical companies and bioethical committees. This is because the analyses describe the results with respect to the main types of cancer (solid tumours and blood cancers), but also with respect to tested oncological therapies (classical chemotherapies and targeted therapies as well as their combinations). Risks and rewards have been assessed for all of these subgroups.

The paper also provides fundamental data for experts designing clinical trials, as it shows how risks and rewards change in the case of different types of treatment (for instance, combining the tested substances or expanding the volunteer group within the framework of dose expansion cohorts).

The paper is the result of many months of collaboration between methodologists, statisticians, doctors, health scientists, oncologists, and ethicists. This meta-analysis is the first in a series of research projects aiming to assess various aspects of risks and rewards in paediatric oncology. The comprehensive data it provides should be appreciated in Poland, where first stage one clinical trial centres are currently being set up.

The project was funded by the National Research Centre. Some part of the project were realised at the Harvard Medical School in Boston.


  1. Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products, EMEA/CHMP/SWP/28367/07 Rev. 1 Committee for Medicinal Products for Human Use (CHMP), 2017.
  2. Hay M, Thomas DW, Craighead JL, et al: Clinical development success rates for investigational drugs. Nat Biotechnol 32:40-51, 2014.
  3. Kimland E, Odlind V. Off-label drug use in pediatric patients. Clin Pharmacol Ther. 2012 May; 91(5):796-801.
  4. Translating discovery into cures for children with cancer, Alliance for Childhood Cancer and American Cancer Society, 2016.
  5. M. Waligora, M.M. Bala, M. Koperny, M.T. Wasylewski, K. Strzebonska, R.R. Jaeschke, A. Wozniak, J. Piasecki, A. Sliwka, J.W. Mitus, M. Polak, D. Nowis, D. Fergusson, J. Kimmelman, Risk and Surrogate Benefit for Pediatric Phase 1 Trials in Oncology: A Systematic Review with Meta-analysis,

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