When we use any medical treatment or drug we are confident it is safe and will help with our illness. How is that confidence achieved? Whenever a new drug is developed, it must go through a rigorous testing process before it can be approved for use. This testing process is essential to ensure the drug's safety and efficacy and includes several stages. There are different types of drugs and different methods for testing them. The first step in testing a new drug is to conduct preclinical trials. This involves testing the drug on animals or lab-grown cells and tissues to assess its safety and determine how it works in the body. Positive results following trials are typically succeeded by clinical tests conducted on humans.
The Meaning of Testing New Drugs
When a new drug is in the process of being developed, it has to go through testing on people to see if they are effective and safe.
Testing usually refers to inoculating or ingesting an active substance that has measurable effects on the human body to test for possible reactions within a population.
Pharmaceutical companies frequently sponsor the testing phase before the medication is approved for public use. The testing itself is usually carried out by independent or affiliated organisations that follow mutually agreed-upon protocols.
Ways of testing new drugs include researching the effects of the substance or substances on different human volunteers or/and its administration methods.
Certain active ingredients that exist in natural forms, such as in plants, will have sometimes been used and tested generationally (for several generations) by people before the more widespread discovery of the compounds.
Communication with people using it over significant periods of time becomes essential to record use and effect.
The cactus plant, Hoodia gordonii, has been traditionally consumed by the hunter-gatherer societies of Southern Africa to suppress thirst and hunger on harsh, difficult days. When a company decided to patent the active ingredient contained in the plant and sell it in different countries overseas, the communities demanded compensation and intellectual properties over the knowledge that they gave of the plants' properties and administration.
The Stages of Testing New Drugs
New drug trials typically start with computer analyses, projections, and tests on lab-grown cells, ideally human cells. Neither computer tests nor lab-grown cells can accurately replicate the conditions within the human body. Still, if problems are found at this stage, it is an indicator that the product needs revising. Because the body's energy is produced inside cells, anything that irreparably damages them is usually deemed unsuitable for the whole organism.
This stage is the safest and can sometimes be the least expensive, generally taking less time to notice results.
The second stage includes animal testing, which is used extensively in the case of new drug development.
It is a hotly debated topic that raises many ethical concerns due to the non-consensual nature of the tests being carried out on the subjects and the harm that can be inflicted upon them, resulting in loss of quality of life or death.
Many animal subjects are considered too different in anatomy and metabolism to be accurate predictors of human drug efficiency. One of this stage's main advantages is that it provides a first-time insight into the drug's effects on a living organism that is genetically close to humans, helping identify any potential side effects. The body mass of the test subjects may also be extrapolated to establish safe dosages in humans.
Testing on human subjects can begin if the drug appears safe at this stage.
The last stage is the clinical stage. Clinical trials are research studies in which people volunteer to test new treatments or interventions.
Often, finding volunteers willing to participate in trials can be difficult.
This is usually conducted in three main phases: phases I, II, and III. Each successive stage tests a more significant number of people and provides additional information about the safety and efficacy of the drug.
Only when a new drug has passed all these trials can it be approved for use by the public.
Drug safety refers to assessing the potential for drugs to cause adverse effects in humans and identifying and characterising those effects. It also encompasses the development of strategies to minimise the risk of drug-related harm and measuring dosages.
Drug efficacy is a measure of how well a drug works in humans, and it also includes the drug's half-life, also known as the time the body takes to eliminate the drug.
Some treatments can take up to 15 years to complete all phases of clinical trialling before the product can be approved and sold on the market. This is because the lab testing of a substance, whilst essential, cannot accurately predict its effects on many people from different demographics. Medical background, sex, and ethnicity are three characteristics that may influence the effects of drugs and their recommended dosages.
Phase I trials test the safety of the medication in a small group of people.
Phase II trials test the effectiveness of the medication in a larger group of people.
Phase III trials compare the results of the phase II trial with a placebo trial to see if the medication is more effective than a placebo. If the medicine is safe and effective, it will be approved for use by the public.
A placebo is a harmless medicine with no active properties, such as a sugar pill, given for the psychological benefit of the patient.
In clinical trials, patients are randomly assigned to receive either the active treatment or a placebo without being informed of which one it is. The placebo-receiving group is known as the "control group".
In a scientific study, a control group is a group of subjects that do not receive the tested treatment. The purpose of a control group is to provide a baseline against which the results of the treatment group can be compared. Sometimes, the control group may receive a placebo or inactive treatment. In other cases, the control group may not receive any treatment.
The results of each stage need to be communicated somehow, right? Scientists use article writing to convey the information gathered from such studies. All medical trial results have to be peer-reviewed. Professionals from the same field, other than those directly involved in the project, will read and evaluate the article. If it is of appropriate quality and the approach used within the study is suitable, it can be approved for publishing. This helps to maintain the integrity of the articles produced in science.
Does New Drug Development End At This Stage?
Yes, if we are talking about releasing the product on the market, but not from a health and well-being perspective.
The gathering of data about the side effects of medication and its efficiency continues even after its approval. This may be known as the Phase IV trial.
Though aspirin was first patented in 1899, it is only in the latest years (2022) that it stopped being recommended in the case of patients at risk of heart attack or stroke in the US.1
Researchers also use clinical trials to look at other aspects of care, such as improving the quality of life for people with chronic illnesses. Clinical trials are one of the final stages of a long and careful research process. Researchers conduct clinical trials to determine if a new intervention, such as a new drug, is safe and effective in people.
Without clinical trials, researchers would not have any scientific basis for saying that a new drug helps patients.
However, even after testing has begun on human subjects, researchers monitor participants closely for potential side effects. The first testing stage in humans is usually conducted on a small group of healthy volunteers. This initial testing is designed primarily to assess the safety of the new drug.
Methods of Testing New Drugs
Historically, drug testing was also a process of trial and error because many active ingredients synthesised today occur in nature in a similar form. This includes aspirin (which can be found as salicylic acid in willow bark), and morphine and codeine (two alkaloids contained in poppy seeds).
A salicylate is any member of a group of chemicals derived from salicylic acid, found naturally in many plants and has various uses in human medicine.
These chemicals serve as a natural defence against herbivores and pathogens.
Most alkaloids are naturally occurring organic compounds that contain at least one Nitrogen atom. They are found in many plants, and some alkaloids are used as drugs, due to their medicinal properties.
Historically, people will have consumed some natural products and noticed their properties before being synthesized in labs worldwide. Sometimes, consumption was done by own initiative, by mistake, or after observing their effects on animals consuming them.
Did you know that drugs may have different ways of being administered, each with possibly different effects on the human body depending on the method? Below we will look at some of them!
Table 1: Some details for different methods of administration for drugs.
| Methods of administration | Details |
| Oral | Oral administration has the advantage that it can be self-administered and includes:- sublingual or buccal, dissolved under the tongue or in the cheeks due to their thin and soft tissue that enables quick absorption into the bloodstream.
- ingestion: swallowing the drug
|
| Injected | Injections typically require needlesand slightly more expertise than oral administration. Injections of new drugs can be:- intravenous: injected into a vein.
- intramuscular: injected into the muscle.
|
| Dermal absorption | The drug enters the body (the bloodstream) through the skin. |
| Inhalation | The inhalation of medicine allows for the absorption of the medication into the bloodstream through the lungs, lined with a large surface area of blood vessels. |
| Rectal | Rectal administration involves the insertion of a drug, typically a suppository, through the rectum (the final section of the large intestine) so that it can be absorbed into the bloodstream through the rectum walls. |
The most popular methods of testing new drugs include blind trials.
- In "single" blind trials, the volunteers do not know whether they receive the actual treatment or a placebo.
- In double-blind trials, neither the doctors nor the volunteers know who receives the treatment or the placebo. The double-blind trials produce the most accurate results because the doctors' expectations, and not just the patients', can sometimes influence the results (this is known as bias).
Testing New Drugs: Types
The three main new drug testing types can be separated into in vitro, in vivo and in silico testing.
In vitro testing ("in glass") is done outside of a living organism. This type of testing is often done on cells or other biological material that has been isolated from an organism.
In vivo is testing that is done on a living organism. This could be done on animals or humans. Clinical trials are one type of in vivo testing.
In silico testing is a type of computer-aided testing that uses models to simulate the behaviours of real-world systems, such as the human body.
New drug testing starts in laboratory settings, where the effects of the drug can be studied in controlled conditions. This typically includes a combination of in vitro testing and computer modelling.
- Preclinical drug trials
- Cells (used in cancer studies and immunology, STEM cells for transplants, tissue-growing, etc.)
- Computer models (Computational Cardiovascular Science, virtual assay software, etc.)
- Animal trials
- Animals frequently tested on (rodents, pigs, dogs, monkeys)
- Human clinical trials
- Volunteers (selected for example from volunteer registries)
Testing New Drugs - Key takeaways
In vivo, in vitro and in silica testing are the three pillars of testing new drugs for efficacy and safety.
New drug testing is nowadays primarily done in controlled conditions. Still, many compounds have only been synthesised from natural origins, such as plants, after being discovered and tested by human communities for centuries through trial and error.
The three essential testing phases of new drugs are preclinical, animal, and clinical trials.
Allowing information influx about the new drugs released on markets even after the successful completion of clinical trials is crucial to ensure safety across different population demographics.
New medicine can be administered in various ways, including buccal, rectal or intravenously.
References
- Aspirin No Longer Recommended to Prevent First Heart Attack, Stroke, webmd, 2022, https://www.webmd.com/heart-disease/news/20220427/aspirin-no-longer-recommended-prevent-heart-attack-stroke. Accessed 23.07.22
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