How do Veterinary Clinical Field Trials work and What is the Procedure adopted ?
A clinical trial is defined as a ‘study which aims to examine under field conditions the safety or efficacy of a veterinary medicinal product under normal conditions of animal husbandry or as part of normal veterinary practice for the purpose of obtaining a marketing authorisation or a change thereof’. The purpose of such trials is to demonstrate or substantiate the effect of the veterinary medicinal product:
• After administration of the recommended dosage;
• To specify its indications and contra-indications according to species, age, breed and sex, its directions for use, any adverse reactions which it may have and its safety and tolerance under normal conditions of use.
It should be noted that animals used in such trials are expected to be under veterinary care and appropriate clinical care. For practical purposes, the HPRA regards clinical trials on veterinary medicines as those relating to trials carried out on the target species using final or near final formulations of a veterinary medicine at the recommended dosage and under field conditions. Such trials are expected to be conducted under Good Clinical Practice conditions under the responsibility of an investigator and under the care of a veterinary practitioner.
Clinical trials are research studies that aim to determine whether a medical strategy, treatment, or device is safe for use or consumption by humans.
These studies may also assess how effective a medical approach is for specific conditions or groups of people.
Overall, they add to medical knowledge and provide reliable data Trusted Source to assist in health care decision-making and guidelines.
To ensure participant safety, trials start with small groups and examine whether a new method causes any harm or unsatisfactory side effects. This is because a technique that is successful in a laboratory or in animals may not be safe or effective for humans.
Fast facts on clinical trials
- Clinical trials aim to find out whether a medical strategy, treatment, or device is safe and effective for humans to use or consume.
- Trials consist of four phases, and they can focus on: treatment, prevention, diagnostic, screening, supportive care, health services research, and basic science.
- A research team will likely include doctors, nurses, social workers, health care professionals, scientists, data managers, and clinical trial coordinators.
- Participation can involve both risks and benefits. Participants must read and sign the “informed consent” document before joining a trial.
- Risks are controlled and monitored, but the nature of medical research studies means that some risks are unavoidable.
What are clinical trials?
The main purpose of clinical trials is research. Trials are designed to add to medical knowledge related to the treatment, diagnosis, and prevention of diseases or conditions.
Share on PinterestClinical trials are research studies that aim to determine whether a medical strategy, treatment, or device is safe for use or consumption by humans.
Studies follow strict scientific standards and guidelines that aim to:
- protect participants
- provide reliable and accurate results
Clinical trials on humans occur in the final stages of a long, systematic, and thorough research process.
The process often begins Trusted Source in a laboratory, where new concepts are developed and tested.
Testing on animals enables scientists to see how the approach affects a living body.
Finally, human testing is carried out in small and then larger groups.
Trials may be carried out to:
- Evaluate one or more treatment interventions for a disease, syndrome or condition, such as drugs, medical devices, or approaches to surgery or therapies
- Assess ways to prevent a disease or condition, for example, through medicines, vaccines, and lifestyle changes
- Evaluate one or more diagnosis interventions that might identify or diagnose a particular disease or condition
- Examine identification methods for recognizing a condition or risk factors for that condition
- Explore supportive care procedures to improve the comfort and quality of life of people with a chronic illness
The outcome of a clinical trial may identify if a new medical strategy, treatment or device:
- has a positive effect on patient prognosis
- causes unforeseen harm
- has no positive benefits or has negative effects
Clinical trials can provide valuable information regarding the cost-effectiveness of a treatment, the clinical value of a diagnostic test, and how a treatment improves quality of life.
Types of clinical trial
All clinical trials have a primary purpose. These can be broken down into the following categories:
- Treatment: Testing new treatments, new drug combinations, or new approaches to surgery or therapy
- Prevention: Examining ways to improve prevention or recurrence of disease through, for example, medicines, vitamins, vaccines, minerals, and lifestyle changes
- Diagnostic: Finding improved testing techniques and procedures for diagnosing diseases and conditions
- Screening: Testing the best method of identifying certain diseases or health conditions
- Supportive care: Investigating procedures to improve comfort and quality of life for patients with a chronic condition
- Health services research: Evaluating the delivery, process, management, organization, or financing of health care
- Basic science: Examining how an intervention works
Why are clinical trials important?
Clinical trials help improve and advance medical care. The studies provide factual evidence that can be used to improve patient care.
Clinical research is only conducted if doctors are unaware of elements such as:
- whether a new approach works effectively in humans and is safe
- what treatments or strategies work most successfully for certain illness and groups of individuals
How do clinical trials work?
Various elements are involved in setting up, running, and following up a clinical trial.
Clinical trials protocol
Share on PinterestA protocol is the written description of a clinical trial. It includes the study’s objectives, design, methods, scientific background, and statistical information.
A trial follows a comprehensive plan, or protocol. A protocol is the written description of a clinical trial.
It includes the study’s objectives, design and methods, relevant scientific background, and statistical information.
Key information to include may be:
- the number of participants
- who is eligible to take part
- what tests will be given and how often
- types of data to be collected
- the length of the study
- detailed information about the treatment plan
Avoiding bias
Researchers must take measures to avoid bias.
Bias refers to human choices or other factors that are not related to the protocol but which may affect the results of the trial.
Steps that can help to avoid bias are comparison groups, randomization, and masking.
Comparison groups
Most clinical trials use comparison groups to compare medical strategies and treatments. Results will show if one group has a better outcome than the other.
This is usually conducted in one of two ways:
- One group receives an existing treatment for a condition, and the second group receives a new treatment. Researchers then compare which group has better results.
- One group receives a new treatment, and the second group receives a placebo, an inactive product that looks like the test product.
Randomization
Clinical trials with comparison groups often use randomization. Participants are allocated to comparison groups by chance rather than by choice. This means that any differences seen during a trial will be due to the strategy used and not because of pre-existing differences between participants.
Masking or blinding
Masking or blinding helps avoid bias by not informing either the participants or the researchers which treatment the participants will be receiving.
Single blind: This is when either the participants or researchers are unaware, of which group is which.
Double blind: This is when both participants and researchers are unaware.
Confounding factors
A confounder can distort the true relationship between two or more characteristics.
For example, one could conclude that people who carry a cigarette lighter are more likely to develop lung cancer because carrying a lighter causes lung cancer. Smoking is a confounder in this example.
People who carry a cigarette lighter are more likely to be smokers, and smokers are more likely to develop lung cancer, but some people may carry a lighter for other purposes.
Not taking this into consideration can lead to false conclusions.
Who is in the research team?
A principle investigator, who is usually a medical doctor, will lead each clinical study.
The research team may include:
- doctors
- nurses
- social workers
- health care professionals
- scientists
- data managers
- clinical trial coordinators
Where are clinical trials conducted?
The location will depend on the type of study and who is organizing it.
Some common locations include:
- hospitals
- universities
- medical centers
- doctors’ offices
- community clinics
- federally-funded and industry-funded research sites
How long do trials last?
This depends on what is being studied, among other factors. Some trials last days, while others continue for years.
Before enrolling in a trial, participants will be told how long it is expected to last.
Designed and organization
There are different types of study, and different ways of organizing them. Here are some study types.
Observational studies
Cohort studies and case control studies are examples of observational studies.
Cohort study
Share on PinterestA cohort study is an observational study in which participants are selected and followed forward in time, to see how likely disease is to develop within the group.
A cohort study is an observational study in which the study population, or cohort, is selected.
Information is gathered to establish which subjects have either:
- a particular characteristic, such as a blood group that is thought to be related to the development of the disease in question
- exposure to a factor that may be linked to a disease, for example, cigarette smoking
An individual could be chosen because they smoke. They may then be followed forward in time to see how likely they are to develop a disease, compared with other people.
This type of study is used to study the effect of suspected risk factors that cannot be controlled experimentally, such as the impact of smoking on lung cancer.
The main advantages of cohort studies are:
- Exposure is measured in advance of disease onset and is therefore likely to be unbiased in terms of disease development.
- Rare exposures can be investigated by suitable selection of study cohorts.
- Multiple outcomes — or diseases — can be studied for any one exposure.
- Disease incidence can be calculated in both the exposed and unexposed groups.
The main disadvantages of cohort studies are:
- They tend to be expensive and time-consuming, especially if they are conducted prospectively, which means moving forward.
- Changes in both exposure status and diagnostic criteria over time can affect the classification of individuals according to exposure and disease status.
- There could be information bias in the concluded outcome because the subject’s exposure status is known.
- Losses to follow-up may present selection bias.
Case control studies
A case-control study can distinguish risk factors for a particular medical condition.
Researchers compare people with a condition and those without it. Working backward through time, they identify how the two groups differ.
Case-control studies are always retrospective — looking backward — because they begin with the outcome and then trace back to investigate exposures.
The main advantages Trusted Source of case-control studies are:
- Findings can be obtained quickly.
- The study can take place with a minimum of funding or sponsorship.
- They are efficient for investigating rare diseases or diseases with a long induction period.
- A wide range of possible risk factors can be examined.
- Multiple exposures can be studied.
- They require few study subjects.
The main disadvantages of case-controlled studies are:
- Incidence data cannot be generated.
- They are subject to bias.
- It can be difficult to obtain accurate, unbiased measures of past exposures if record keeping is inadequate or unreliable. This is called information bias.
- Selection of controls can be problematic. This may introduce selection bias.
- The chronological sequence between exposure and disease may be hard to identify.
- They are not appropriate for examining rare exposures, unless the exposure is responsible for a large percentage of cases.
Nested case-control study
In a nested case-control study, the groups — cases and controls — come from the same study population, or cohort.
As the cohort is followed forward, the cases that arise become the “cases” in the case-control study. The unaffected participants of the cohort become the “controls.”
Nested case-control studies are less costly and less time-consuming when compared with a cohort study.
Incidence and prevalence rates of the disease can occasionally be projected from a nested case-control cohort study. This is not possible from a simple case-control study, as the total number of exposed individuals and the follow-up times are usually unknown.
The main advantages of nested case-control studies are:
- Efficiency: Not all of the participants of the cohort require diagnostic testing.
- Flexibility: They allow the testing of hypotheses that were not anticipated when the cohort was planned.
- Reduction of selection bias: Cases and controls are sampled from the same population.
- Reduction of information bias: Risk factor exposure can be assessed with the investigator blind to case status.
The main disadvantage is that the results have lower authority, due to the small sample size.
Ecological study
An ecological study looks at the relationship between exposure and outcome of the population or community.
Common categories of ecological study include:
- geographical comparisons
- time-trend analysis
- studies of migration
The main advantages of ecological studies are:
- They are inexpensive, as routinely collected health data can be utilized.
- They are less time-consuming than other studies.
- They are uncomplicated and straightforward to understand.
- The effect of exposures that are measured over groups or areas — such as diet, air pollution, and temperature — can be investigated.
The main disadvantages of ecological studies are:
- Errors of deduction known as ecological fallacy can occur. It happens when researchers draw conclusions about individuals based solely on the analysis of group data.
- Exposure to outcome relationships is difficult to detect.
- There is a lack of information on confounding factors.
- There may be systematic differences between areas in how exposures are measured.
Experimental studies
Apart from observational studies, there are also experimental studies, including treatment studies.
Randomized controlled trials
Share on PinterestA randomized controlled trial randomly allocates individuals either to receive or not receive a particular intervention (consisting of two different treatments or treatment and placebo).
A randomized controlled trial (RCT) randomly allocates individuals either to receive or not receive a particular intervention.
One of two different treatments will be used, or a treatment and a placebo.
This is the most effective study type for identifying which treatment works best. It reduces the influence of external variables.
The main advantages of RCTs are:
- There is no conscious or subconscious bias on the part of the researcher. This essentially guarantees external validity.
- Confounding variables such as age, gender, weight, activity level, and so on, can be canceled out, as long as the sample group is large enough.
The main disadvantages of RCTs are:
- They are time-consuming.
- They can be expensive.
- They require large sample groups.
- Rare events can be difficult to study.
- Both false-positive and false-negative statistical errors are possible.
Adaptive clinical trial
An adaptive design method is based on collected data. It is both flexible and efficient. Modifications can be made to the trial and the statistical procedures of ongoing clinical trials.
Quasi-experiment
Quasi-experimental, or “nonrandomized” studies, include a broad range of intervention studies that are not randomized. This type of trial is frequently used Trusted Source when an RCT is not logistically feasible or ethical.
Hierarchy of evidence
A number of hierarchies of evidence have been founded to enable various research methods to be ranked according to the validity of their findings.
Hierarchies of evidence make it possible to rank various research methods according to the validity of their findings.
Not all research designs are equal in terms of the risk of error and bias in their results. Some methods of research provide better evidence than others.
Below is an example of the hierarchy of evidence-based medicine in the form of a pyramid Trusted Source, ranging from a lower quality of evidence at the bottom to high-quality evidence at the top.
Phases of a clinical trials
Medical research studies are divided into different stages, called phases. For drug testing, these are defined by the FDA.
Early phase trials investigate the safety Trusted Source of a drug and the side effects it may cause. Later trials test if a new treatment is better than an existing treatment.
Phase 0 trials: Pharmacodynamics and pharmacokinetics
Phase 0 is an exploratory phase that helps provide clinical information for a new drug at an earlier phase.
This phase:Trusted Source
- is conducted early in phase 1
- involves very limited human exposure
- has no therapeutic or diagnostic intent, being limited to screening and microdose studies
Phase 1 trials: Screening for safety
After phase 0, there are four more phases of trials in humans. These often overlap. Phases 1 through 3 take place before a license is granted.
Phase 1 guidelines involve:
- between 20 and 80 healthy volunteers
- verification of the most frequent side effects of the drug
- finding out how the drug is metabolized and excreted
Phase 2 trials: Establishing effectiveness
If phase 1 studies do not reveal unacceptable toxicity levels, phase 2 studies can begin.
This involves:
- between 36 and 300 participants
- collecting preliminary data on whether the drug works in people with a certain disease or condition
- controlled trials to compare those receiving the drug with people in a similar situation who are receiving a different drug or a placebo
- continued safety evaluation
- studies of short-term side effects
Phase 3 trials: Final confirmation of safety and effectiveness
If phase 2 has confirmed the effectiveness of a drug, the FDA and sponsors will discuss how to conduct large-scale studies in phase 3.
This will involve:
- between 300 and 3,000 participants
- gathering further information on safety and effectiveness
- studies of different populations
- examining various dosages to determine the best prescription amount
- using the drug in combination with other drugs to determine effectiveness
After this phase, the complete information on the new drug is submitted to the health authorities.
Review meeting
If the FDA approve the product for marketing, post-marketing requirement and commitment studies are conducted.
The FDA use these studies Trusted Source to collect further safety, efficacy or optimal use information about the product.
New Drug Application
Share on PinterestAfter the application is reviewed and before phase 4 trials, the FDA reviewers will either approve the new drug application or issue a response letter.
A drug sponsor will complete a New Drug Application (NDA) to ask the FDA to consider approving a new drug for marketing in the U.S.
An NDA includes:Trusted Source
- all animal and human data
- analysis of data
- information regarding drug behavior in the body
- manufacture details
The FDA has 60 days to decide whether to file it to be reviewed.
If they decide to file the NDA, the FDA review team is assigned to evaluate the sponsor’s research on the drug’s safety and effectiveness.
The following steps must then take place.
Drug labeling: The FDA reviews the drug’s professional labeling and confirms appropriate information is shared with consumers and health professionals.
Facility inspection: The FDA inspect the facilities where the drug will be manufactured.
Drug approval: FDA reviewers either approve the application or issue a response letter.
Phase 4 trials: Studies during sales
Phase 4 trials take place after the drug has been approved for marketing. They are designed to include:
- over 1,000 patients
- comprehensive experience in evaluating the safety and effectiveness of the new medicine in a larger group and subpopulations of patients
- comparison and combination with other available treatments
- evaluation of long-term side effects of the drug
- detection of less common adverse events
- cost-effectiveness of drug therapy compared with other traditional and new therapies
Safety report
After the FDA approves a drug, the post-marketing stage begins. The sponsor, usually the manufacturer, submits periodic safety updates to the FDA.
Who sponsors clinical trials?
Clinical trials and research can cost hundreds of millions of dollars. Groups that fund trials may include:
- pharmaceutical, biotechnology, and medical device companies
- academic medical centers
- voluntary groups and foundations
- National Institutes of Health
- government departments
- physicians and health providers
- individuals
Who can participate?
The protocol defines who is eligible to participate in a trial.
Possible inclusion criteria may be:
- having a specific illness or condition
- being “healthy,” with no health condition
Exclusion criteria are the factors that exclude some people from joining a trial.
Examples include age, gender, a specific type or stage of a disease, previous treatment history, and other medical conditions.
Possible benefits and risks
Taking part in clinical trials can have both benefits and risks Trusted Source for participants.
Possible benefits of clinical trials include the following:
- Participants have access to new treatments.
- If a treatment proves successful, participants will be among the first to benefit.
- Participants who are not in the group receiving a new treatment may receive the standard treatment for the particular condition, which may be as good or better than the new approach.
- Health is closely monitored and supported by a team of health providers.
- Information gathered from clinical trials adds to scientific knowledge, may help others, and ultimately improves health care.
Possible risks include:
- Standard care for a particular condition can sometimes be better than the new strategy or treatments being studied.
- The new approach or treatment may work well for some participants but not necessarily for others.
- There may be unexpected or unforeseen side effects, especially in phase 1 and phase 2 trials and with approaches such as gene therapy or new biological treatments.
- Health insurance and health providers do not always cover patient care and costs for those participating in clinical trials.
What does giving consent mean?
Share on PinterestParticipants are expected to read the consent document thoroughly, decide whether they want to enroll and sign before they can be included in the trial.
The informed consent document explains the risks and potential benefits of taking part in a clinical trial.
Elements that must appear in the document include, among others:
- purpose of research
- foreseeable risks of discomforts
- possible benefits
Participants are expected to read the consent document Trusted Source thoroughly, decide whether they want to enroll and sign before they can be included in the trial.
Are clinical trials safe?
The FDA works to ensure that anyone who is considering joining a trial has access to all the reliable information they need to make an informed choice, including information about the risks.
While risks to participants are controlled and monitored, some risks may be unavoidable, due to the nature of medical research studies.
How are participants protected?
Share on PinterestGood clinical practice (GCP) is defined as a standard for the design, conduct, performance, monitoring, auditing, recording, analysis and reporting of clinical trials or studies.
Safety of participants is a high priority issue. In every trial, scientific oversight and patient rights contribute to their protection.
Good clinical practice (GCP) aims to ensure Trusted Source that ethical and appropriate procedures are followed in trials.
GCP compliance provides the public with confidence that the safety and rights of participants are protected.
It aims to:
- to protect the rights, safety, and welfare of participants
- to guarantee that data collected is reliable, has integrity, and is of an appropriate quality
- to provide guidelines and standards for the conduct of clinical research
The foundations of GCP were first laid out in 1947. The main points were that, during any trials, researchers must guarantee:
- voluntary participation
- informed consent
- minimization of risk
Over time, additions have ranged from establishing additional protection for vulnerable populations to providing guidance to bodies carrying out research.
Patient rights
Ways of protecting patient rights include the following:
Informed consent is the process of supplying clinical trial participants with all of the facts about the trial. It happens before the participants agree to take part and during the course of the trial. Informed consent includes details about the treatments and tests that may be received and the possible benefits and risks.
Other rights: The informed consent document is not a contract; participants may withdraw from the study at any time regardless of whether or not the trial is complete.
Rights and protection for children: A parent or legal guardian must give legal consent if the child is aged 18 years or younger. If a trial may involve a risk that is greater than minimal, both parents must give permission. Children over the age of 7 years must agree to be involved in clinical trials.
What are clinical trials?
A clinical trial is a research study conducted in human beings with the goal of answering specific questions about new therapies, vaccines or diagnostic procedures, or new ways of using known treatments. Clinical trials are used to determine whether new drugs, diagnostics or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that help people.
After researchers test investigational new therapies or procedures in the laboratory and in animal studies, those with the most promising possibilities are moved into human clinical trials. Clinical trials are broken down into different phases. During a trial, more and more information is gained about the potential treatment, its risks and how well it may or may not work, along with aspects related to quality of life.
What are the different phases of a clinical trial?
Clinical trials are categorized as Phase I to IV trials. They are generally described as follows:
Phase I (small number of participants, normally between 6-10 healthy volunteers, or very sick patients for whom treatment options are lacking)
Phase I studies are designed to allow scientists and medical doctors to understand what effects an investigational compound has in human subjects. The goal is to study what happens to the compound in the body from a safety and tolerability point of view after it is swallowed, injected or infused. .Study participants are monitored for the occurrence and severity of any side effects that they may experience.
Phase II (once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups of patients, generally 20-300 depending on the type of disease)
Phase II studies are designed to begin to evaluate the safety and efficacy of an investigational medicine in patients, and often used to determine if different dosages of the treatment have different effects. The patients are given various doses of the compound and closely monitored to compare the effects and to determine the safest and most effective dosing regimen. In many instances, multiple Phase II studies are conducted to test the compound in a variety of patient populations or indications.
Phase III (carried out on large patient groups, 300–3,000 or more depending upon the disease being studied)
Phase III studies are designed to confirm the safety and efficacy of an investigational medicine. Large numbers of patients are generally involved in order to adequately confirm benefit and safety. These studies, as in the earlier phases, may involve one or more ‘treatment arms’, which allow for the safety and efficacy of the new investigational drug to be compared to other available treatments, or to be tested in combination with other therapies. Information obtained from Phase III studies is used to determine how the compound is best prescribed to patients in the future.
Phase IV (also known as Post-Marketing Surveillance Trials)
Phase IV studies take place after the medicine has received regulatory approval (market authorization) and are designed to provide broader efficacy and safety information about the new medicine in large numbers of patients, subpopulations of patients, and to compare and/or combine it with other available treatments. These studies are designed to evaluate the long-term effects of the drug. Under these circumstances, less common adverse events may be detected.
What are the ethical principles that govern clinical trials?
Ethical clinical research is guided by the principles of nonmalificence, respect, beneficence and justice.
- Nonmalificence is the duty to cause no harm. This principle has its roots in the Hippocratic Oath. The ethical issue at the core of clinical research is whether the outcome of the research can be reasonably expected to provide benefit to society without doing any harm to the individuals enrolled in the trial.
- Respect for persons is embodied in informed consent, dictating that information is exhaustive and provided in a manner that is understandable, that the subject’s cooperation is voluntary, and that all information pertaining to the subject is held in confidence.
- Beneficence is demonstrated by a thorough risk/benefit assessment, recognizing that benefits can be direct, collateral, and/or altruistic. Similarly, risks are considered in physiologic, psychological, and socioeconomic terms. For a clinical trial to be considered ethical, there must exist a sufficient body of scientific/medical evidence to justify exposure of individuals to the risks of the trial. There must be clear medical need, and the potential benefits to be gained by the research must be weighed against the possible risks to the participating person in both safety and effectiveness of the drug or intervention being studied.
- The principle of justice takes into account all the processes by which populations are selected for study to ensure that the results benefit the community, avoid exploiting vulnerable populations, and include individuals who may be likely to benefit.
What are the rights of participants in a clinical trial?
Participants are entitled to a clinical trial that adheres to all legal and ethical standards. In addition, participants have a right to:
- A clear, transparent Informed Consent process before they agree to join the trial
- Withdraw from the trial at any point in time
The Informed Consent process aims at answering any and all questions that might be relevant to a participant’s decision to agree or decline to join a trial. Only participants who, after having all their questions answered, sign an Informed Consent form can enter the trial. With their signature, participants confirm that they believe they have been given all the important facts about a trial, that they understand them, and that they decided to take part in the trial of their own free will.
An Informed Consent document is not a contract. Therefore, a participant may change his or her decision – any participant has the right to withdraw at any point of the trial. A withdrawal will not affect the participant’s relationship with their doctor nor will it result in a loss of benefits to which the participant is otherwise entitled. Potential medical risks of a sudden withdrawal from the trial should be detailed in the Informed Consent document.
How is the privacy of participants protected?
If a patient agrees to join a trial, some people will need to be told about the participation. These people are:
- The patient’s primary physician who is responsible for their healthcare on a day-to-day basis
- The doctor and research team looking after the patient in the trial
The fact that someone is taking part in a trial will be written in that patient’s medical notes. Investigators cannot tell anyone else about a participation in a trial unless the patient gives his or her permission.
During the trial, all of the information collected about the participants will be kept confidential, as with any other medical records. When investigators publish the results of a trial, they are not allowed to include any information that would identify people – a patient’s name will not be used in any reports or publications.
The clinical trial protocol will define what is to be done with samples and information of participants. Specific sections within this document will detail for how long samples and information must be kept before they are destroyed. If samples and/or information are to be used further, then this will be either:
- included in the original trial protocol
- be part of the informed consent a patient signs prior to his participation in the trial
- be written up in a specific informed consent which the patient will also be asked to sign.
Are the standards for clinical trials in developing countries different?
Conduct of clinical trials in developing countries presents a unique set of ethical issues. Where Roche undertakes clinical trials in developing countries, the same high standards of ethical conduct and scientific integrity will be adhered to, with the ultimate goal of delivering relaible results at the conclusion of the clinical research. For further information see
Clinical Trials in Low and Middle Income Developing Countries .
Where the results from a Roche Sponsored Clinical Trial in a low or middle income country are used for the purposes of registering the Roche medicinal product in another country, Roche commits to apply for marketing authorization of the medicinal product in the low or middle income country in which the trial was conducted.
The Fundamentals of Animal Testing in Clinical Research
Because humans and animals are biologically similar, animal testing in clinical research helps researchers learn how to prevent, treat, and cure human diseases and ensure product safety.
While several different approaches are used during clinical research, traditional biomedical research involving animal testing to develop new treatments and drugs may be a strategy of the past after the FDA Modernization Act 2.0 was signed in December 2022. This act allows organizations to use scientifically rigorous, proven, non-animal testing methods, such as cell-based assays and computer models, when suitable.
ANIMAL TESTING
Dating back to 500 BC in ancient Greece, animal experimentation has been used throughout history in the field of biomedical research. Animal testing allows researchers to examine health problems affecting humans and animals and assure the safety of new drugs and medical treatments.
Today, standard animal models typically include mice and rats because of their anatomical, genetic, and physiological similarity to humans and their ease of maintenance and size, short life cycle, and abundant genetic resources. According to Missouri Medicine research, rats, mice, and humans have approximately 30,000 genes each — roughly 95% of which are shared by all three species.
The European and North American house mouse (Mus musculus) is biomedical research’s most commonly used experimental model organism. However, for behavioral and physiological studies, rats are most commonly used because they are more social and mimic human behavior better than mice. For more than 150 years, the laboratory rat (Rattus norvegicus) has remained the choice model for these complex fields of study.
Using new gene-editing tools, such as CRISPR-Cas9, scientists can make precise changes to the genomes of larger mammals, such as primates, pigs, sheep, dogs, cats, rabbits, hamsters, and guinea pigs, to learn more about diseases, disorders, and prevention and treatment methods that affect both humans and animals.
Non-human primates (NHPs), a group of hominins, apes, and monkeys that are biologically and evolutionally similar to humans, are used in several research fields because they are susceptible to many of the same health problems and because they have short life spans, making it easy for researchers to study entire life cycles or several generations.
The NHP species most commonly used in biomedical research are macaques (Macaca mulatta) due to their affordable breeding and housing requirements and suitability as a model for high-priority diseases like HIV, obesity, and cognitive aging.
ANIMAL WELFARE
Although federal organizations have developed clinical laws and regulations to make animal testing more humane, the practice of using animals for biomedical research has been under intense scrutiny by animal rights and welfare groups for many years for their lack of oversight into the treatment of excluded animals.
What Is the Animal Welfare Act?
Passed in 1966 and enforced by the USDA and APHIS, the Animal Welfare Act (AWA) addresses how warm-blooded animals are cared for and treated in laboratory settings regarding their housing, feeding, cleanliness, ventilation, and medical needs. The act also requires using analgesic drugs for potentially painful procedures and interventions.
However, in a provision of the 2002 Farm Bill, laboratory rats, mice, and birds were explicitly excluded from the Animal Welfare Act, ending a longstanding debate among animal rights advocates and researchers over whether the USDA should be responsible for regulating certain species of rodents and birds bred for research purposes. The act also excludes horses not used for research and farm animals.
Several government organizations, including the United States Department of Health and Human Services, the Public Health Service, and the Office of Laboratory Animal Welfare, control the use of mice, birds, and rats in laboratory research. A separate piece of legislation, the Health Research Extension Act, sets the standard of care and housing for mice, rats, and birds excluded under the AWA if federally funded.
What Is the Health Research Extension Act?
The Health Research Extension Act of 1985 provides a legislative mandate for creating and enforcing guidelines for the care and treatment of animals — such as mice, rats, and birds — used in biomedical and behavioral research funded by the Public Health Service (PHS).
AWA-covered facilities that use animals for research, testing, or educational purposes are required to form an Institutional Animal Care and Use Committee (IACUC) — comprised of scientists, veterinarians, and at least one member of the general public who is not institution-affiliated — to oversee their animal programs. With roughly 1,400 IACUCs associated with research, testing, and educational laboratories across the US, these committees are responsible for inspecting laboratories and teaching facilities.
Before animals can be used, IACUCs are required to review and approve all research and education protocols. To minimize suffering, they also look for evidence that the investigator has genuinely tried to identify animal alternatives if the research might cause painful or distressing sensations.
If it is decided that animal subjects must be used, IACUCs ensure a plan is in place for alleviating pain and distress. To assist institutions, the Guide for the Care and Use of Laboratory Animals, an internationally accepted primary resource for animal care and use, is required for the proper care, use, and humane treatment of research animals.
HOW MANY ANIMALS ARE USED IN RESEARCH?
Although alternative non-animal models exist, the Humane Society of the United States estimates that more than 50 million animals are used in research, education, and testing yearly in the US. Globally, the RSPCA suggests that more than 100 million animals are used in research and testing each year.
In 2019, data from the US government suggests that 797,546 laboratory animals were used in research — an increase of 2.2% from the previous year — and that 137,225 animals were kept in research facilities but were not utilized in any studies.
United States animal research statistics from 2019 indicate that 53% of research was conducted on guinea pigs, hamsters, and rabbits, while 9% was conducted on dogs and cats and 9% on NHPs.
Globally, roughly 100,000–200,000 NHPs are used yearly for research purposes. According to Columbia University, the use of NHPs is on the rise as they have been proven particularly valuable in monoclonal antibody research, in which NHPs are the only animal approved for preclinical safety studies.
Because the AMA excludes mice, rats, and birds, the US does not track how many of these animals are used for research each year. However, some suggest these numbers may be comparable to other developed countries that do.
For example, in Great Britain, 2.88 million procedures were carried out in living animals in 2020, with a majority (92%) of procedures performed on mice, fish, or rats. According to Stanford University, approximately 95% of the total animals needed for medical and scientific purposes in the US are rodents.
When possible, researchers are committed to conducting studies using alternative methods, including cell-based testing, 3D tissue cultures, computational and mathematical models, noninvasive diagnostic imaging, and human testing instead of animal models. However, some health conditions, unfortunately, can only be studied in a living organism to ensure human safety and efficacy.
Compiled & Shared by- Team, LITD (Livestock Institute of Training & Development)
Image-Courtesy-Google
Reference-On Request.
