Public interest in the pharmaceutical industry has never been higher.  

Since the pandemic years – when the processes of vaccine development, testing, and validation were widely and constantly discussed in the media – until today, a moment when technological, political, and economic issues have led to rapid changes in the market and in the way medications are viewed by society, public curiosity about how this billion-dollar industry, responsible for promoting global health, works has only increased.  

This is reflected in the desire to understand the "step by step" of the approval of a new medication.  

After all, how are candidates for new medications tested – in what manner and for how long – to ensure efficacy and safety? Are there 'guinea pigs' who accept to receive doses of a new drug without knowing in advance what they may cause in the body? Or is there a more structured process, involving stages that must be gradually fulfilled, each one ensuring a bit more information about the molecule under study, until a robust body of evidence related to the efficacy of the new drug is formed?  

These are some of the questions we will address today.  

Understanding the stages that take a medication from laboratory testing benches to pharmacy shelves is a fascinating process that sheds light on an industry whose details are still largely unknown to the general public, but which is increasingly present in all our lives.  

In particular, we will discuss the significant role of clinical research in the approval of new drugs – a rigorous and globally validated methodology that helps turn ideas into treatments.  

Clinical Research: turning medication ideas into new treatments

There is a reason why clinical research is the core of this discussion. After all, it represents the bridge that connects research laboratories to pharmacy shelves.  

Through rigorous testing and validation, based on solid scientific evidence and governed by a broad compendium of legal determinations, innovations in the pharmacological field can be validated as safe and effective and delivered in the form of a new medication for patients.  

The main differentiator of these studies is the presence of human beings as a factor to be analyzed – that is, research participants, both healthy and sick, who will receive a new treatment and be evaluated to discover how the new drug works in 'real' situations, with real people, in a biologically complex environment. That is what a medication is created for, and clinical research is the final step to validate it.  

The goal is the protection of the public and the transparency in the medication production process. Each step is regulated, tested, recorded, validated. The results are public and referable. They are analyzed by independent panels and can be consulted by the medical and scientific community.  

The quality of clinical research can be directly linked to the continuous evolution of public health worldwide.  

How it all begins: laboratory tests and animal models

Ensuring the safety of a medication is fundamental for its use in humans. Even if there is anecdotal evidence of positive health effects, or even if the most advanced computational models 'guarantee' that a certain molecule, in a certain dose, will decisively act in the treatment of a disease, there will never be any kind of testing in people before potential adverse effects are identified, or a safe dosage to be administered has been determined.  

How can we understand these parameters without using humans as 'testers' beforehand?  

The secret lies in the preclinical stages of studies. They are crucial in obtaining a robust body of evidence indicating the efficacy and safety of the new medication. Without this evidence, there are no tests in humans. 

Preclinical studies involve in vitro analyses (using cell cultures) and in vivo (with animal models), in order to obtain information such as:  

• Pharmacodynamic profile of the active ingredient in question: that is, how it acts in the body;  

  
  

• Your pharmacokinetic profile: how the body absorbs, metabolizes, distributes, and excretes the molecule(s) under study;  

  
  

• The toxicity profile: determining the ideal dose for administration of the medication in order to maximize therapeutic effects and minimize the risks of harm to the body. Potential toxic effects on various organs and systems are evaluated, including the possibility of neurotoxicity and teratogenicity (risk of congenital malformation). 

  
  

The results of these stages are compiled in a rigorous and standardized manner, using guidelines determined by regulatory bodies and agencies. In other words: these preclinical stages are so crucial that there is already strong control over the data and results, which must adhere to strict scientific and ethical standards. If a medication is not approved in these in vitro stages and with animal models, it will not reach pharmacies.  

The four stages of Clinical Research

Having overcome the ‘challenges’ of preclinical studies, the potential new medication enters one of the most notable phases of the development process: contact with human beings. The clinical research has four main stages, involving an increasing number of volunteers. Let’s learn details about each one.  

PHASE I: Identifying the right dose  

As the old saying goes, “the difference between medicine and poison may lie in the dose.” And finding the ideal dosage is only possible in tests with people, when the medication will be evaluated amidst the infinite complexity of the human body and the variety of health and physiology 'compositions' of each volunteer.  

It’s worth noting that a safe dosage range has already been validated previously in preclinical tests. In this Phase I, the aim is to optimize the ideal dose.  

In the first phase of clinical studies, a small group of participants (approximately 20 to 100) receives variable doses of the medication under study, based on the safety profiles identified by preclinical tests. Participants can be either healthy individuals (which is more common) or patients with the disease the medication aims to treat.  

After the drug administration, participants are periodically tested to evaluate how the new molecule(s) is (are) being processed by the body, in a manner similar to what was done in preclinical tests, that is, measuring absorption, metabolism, distribution, and excretion profiles. The objective is to ensure that the active ingredient, in the form it was administered, is safe and produces tolerable side effects.  

It is, therefore, the design of a safety profile – the efficacy in treating a disease is not being tested at this point. This is the mission of the second phase of clinical research.  

PHASE II: Determining efficacy  

While the safety profile of the potential new medication continues to be tested (in fact, it never stops being tested, even after the product starts being sold), Phase II brings the novelty of assessing, in a preliminary manner, the efficiency of the molecule as a health treatment. To do so, it is clear that it must be tested on people who have the disease the medication aims to treat. In other words: here, healthy participants exit, and those who most need a new treatment enter.  

It may seem a straightforward and reasonably clear process, however this is one of the phases that generates the most unease and doubts in the general public.  

This is because Phase 2 is where the 'famous' randomized studies with placebos occur – when part of the volunteers receives the new active ingredient and part takes only a placebo, both without knowing which is which. This is absolutely crucial for the quality of an experiment. Decades of medical studies have proven the enormous influence that psychological factors have on the course of a disease and its treatment. That is precisely why this type of examination was created, to evaluate, in the clearest and honest way possible, whether a new treatment truly brings benefits to a patient’s health.  

It is important to highlight that, even in cases where the participant is allocated to the placebo arm, they do not go without treatment. All participants continue to receive the standard therapy already approved and available for the disease, ensuring full coverage of treatment and strictly respecting the ethical principles of clinical research. 

Phase II aims, therefore, to certify the results of Phase I and to expand the therapeutic understanding of the active ingredient, in a scenario that involves people who have the disease the new medication aims to treat.  

Approximately 100 to 300 patients participate in Phase II studies.  

PHASE III: Confirming the hypotheses  

A test medication that passed Phase II demonstrated potential that it can indeed bring benefits to patients' health and treat specific diseases safely. What remains is to ensure its efficiency in the broad and diverse context of the general population.  

To that end, Phase III involves a relatively large number of participants (numbers can reach up to 10,000), who will be monitored regarding aspects such as:  

• perception of the drug's effectiveness,  

  
  

• proof of positive effects in the body,  

  
  

• presence and intensity of side effects and  

  
  

• comparison of all these factors with already existing and approved treatments for the disease in question.  

This is the "final phase" that must be passed to ensure approval by regulatory agencies.  

PHASE IV: Monitoring with the public  

Phase IV occurs 'in the real world'. In this stage, the new medication has already been approved for commercialization and is in use by the population. This does not mean, however, that it is no longer monitored by the pharmaceutical industry.  

This phase is known as ‘post-marketing,’ or post-market entry, and it tracks the evolution of the medication’s use, reports of side effects (that may not have been perceived in previous stages, given the reduced number of participants), and possible off-label uses of the active ingredient.  

In many cases, Phase IV is considered ongoing, without temporal limitations, with constant monitoring in order to build the drug’s safety profile in different populations, as well as its performance profile in conjunction with other health treatments, whether already established or new.  

As we have seen above, there is great complexity in the approval and commercialization process of a new medication. There are several 'checkpoints' along this path that seek to guarantee (the word is used in its strictest sense here), in a systematic and scientifically accurate manner, the safety and efficacy of a drug. All stages are governed by a set of predetermined rules that must be followed precisely.  

Who regulates this data?

Medication is serious business. Public health is even more so. During the COVID-19 pandemic, we learned abruptly what this means: there was much discussion regarding the use of prevention and treatment methods that were not scientifically proven against the disease. Should the public be allowed to use potentially beneficial medications, but without real proof? Should public authorities distribute vaccines that had not yet been fully tested? Following traditional protocols – strong guarantees of safety, efficacy, and reliability – was more important than offering quick-fix solutions, which might be ineffective?  

What became clear from these decisions is that placing any medication on the market is not a simple, quick, or arbitrary process that can skip steps. The regulatory body that determines the requirements for the preparation and commercialization of drugs is one of the best-coordinated in global terms, and here in Brazil, ANVISA plays a fundamental role in protecting the health of the population, being one of the most rigorous regulatory agencies in the world.  

It is ANVISA that monitors the conduct of clinical studies and research and checks whether they follow the appropriate scientific, medical, ethical, and quality criteria. Its guidelines are aligned with the major global regulatory agencies (through shared protocols like the Council for Harmonisation (ICH) and Good Clinical Practice (GCP)), creating a context where a drug approved here in Brazil has a great chance of being released for use in other countries as well. It is not easy to be approved by ANVISA, but seeking this approval opens doors worldwide.  

It is important to note that, although we are talking about 'bureaucracy,' the process of evaluating and approving medications is quite dynamic. Both ANVISA and other global regulatory agencies respond relatively quickly to changes in the health world, creating new rules and updating protocols to make them more suitable for new times and new scientific evidence.  

For example, over the past few years, the adoption of modern analytical methods and new testing methodologies has allowed to improve the flow of validation and testing of molecules, and this has already been reflected in protocol updates from these entities, resulting in faster stages of drug validation, while maintaining the same quality in the final result.  

The (not small) challenges of Clinical Research

Conducting clinical research for new medications is far from being a simple and quick process. On the contrary, the rigor in data control and respect for participants' health requires maximum care and attention, an experienced technical team, and adequate infrastructure. All of this comes at a cost, both in terms of time and investment, which helps explain why it is still so expensive to bring a new medication to market.  

The greatest complexity related to clinical research is the human factor. After all, they involve tests with research participants, both healthy and sick, who need to receive yet-to-be-proven medications, but in a safe and non-harmful manner to health. These individuals must be carefully selected, monitored over a long period, and in a scientifically accurate manner, and must strictly follow the suggested treatment protocol on their own. Notice how many variables exist for each of the factors above. All of them are taken into account in the final results.  

The recruitment of patients is one of the most challenging stages of clinical research. That’s why the pharmaceutical industry often relies on the support of specialized partners, who have access to healthcare centers and databases with potential volunteers. These participants must meet specific health criteria, in addition to being carefully informed about the study's objectives, procedures, and potential risks. All this information is included in the Informed Consent Form (ICF), a detailed document that clearly presents the possible effects of the medication, the exploratory nature of the research, and the participant's rights. It is crucial to emphasize that participation is entirely voluntary and the individual can leave the study at any time, without any penalties or harm to their conventional treatment. 

Once included in the study, the participant must rigorously follow the use of the medication as instructed: in the dose, at the time, and in the indicated manner. Their health is constantly monitored by a specialized team, ensuring safety throughout the process. It is a complex journey that requires precision, care, and technical expertise to guarantee not only the validity of the results but, above all, the integrity and well-being of the volunteers. 

Clinical research requires centers of excellence

As they represent the final stage before the approval of a medication, clinical research follows the most rigorous control and quality standards intended for the pharmaceutical industry. To meet these, it is necessary to work alongside highly qualified partners.  

Participating in clinical studies are hospitals and academic health and research centers (usually linked to large universities), public and private hospitals, specialized clinics, and companies focused on health. It is essential that they have a technical team and infrastructure capable of managing examinations with patients, monitoring them, and delivering high-quality analyses.  

The ideal model for conducting clinical research is in specialized centers, locations that combine, in the same infrastructure, suitable environments for receiving and monitoring patients, qualified teams, analytical laboratories, and optimized operational procedures, generating a flow of high-quality information and reducing the 'noise' always present in studies with humans.  

In Brazil, SYNVIA is a reference example in clinical research, from phase I to IV. The company has more than 20 years of experience in analyses for the pharmaceutical industry, being one of the most respected multisite research centers in the country. One of its main differentiators in relation to clinical research is the human factor: there are more than 150,000 registered volunteers in the database (at least 50,000 of whom are contacted every month by the company to participate in tests), allowing the inclusion of broad groups with the ideal profile for each type of study.  

After the selection for participation, volunteers have access to an infrastructure specially designed for conducting experiments: there are more than 160 beds in four wards, with average assistance 24 hours a day, and integration with analytical laboratories, which house state-of-the-art equipment.  

Thus, with intelligent monitoring and a fluid and optimized process for data acquisition, it is possible to reduce the time of studies and improve the yield of reliable results – bottlenecks that usually drive up costs in clinical stages in other situations. Learn more about the services offered by SYNVIA and its role in clinical research at this link.  

Clinical Research: a synonym for quality, rigor, and life

Considering all the points discussed above, it becomes easier to understand why bringing a new medication to market can take years – even decades.  

In the fast-paced and immediate world we live in, waiting so many years may seem like a terrible waste of time and resources; however, rushing the approval process could result in harm to health or ineffective treatments, and that is something inconceivable. Quality demands time and investment. The results are reflected in a growing and constant improvement in the quality of life of the population. That is invaluable.  

It is not an exaggeration to say that most people today can enjoy a healthy life thanks to medications – at least once in their lives, everyone has taken a medication, whether an antibiotic, an antipyretic, or even an analgesic – which resulted in relief from symptoms, strengthening of health, or even cure. In all these cases, we can be sure that the substance used underwent clinical research, rigorous tests that ensured its efficacy and safety.  

Clinical research, with all its rigor, controls, and 'bureaucracies,' is behind the greatest advances in public health of the last century. It is precisely this adherence to solid data that allows the industry to progress ever stronger, fostering technological advancements and enabling, each year, new forms of treatment for millions of people.