Clinical trials are the experiments or observations made in clinical studies. Biomedical research studies or prospective behaviors such as human participants are designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as new vaccines, drugs, dietary options, dietary supplements, and medical devices) and known interventions that guarantee research Furthermore. and comparison. Clinical trials yield data on safety and efficacy. They are performed only after they receive the approval of the health authority/ethics committee in the country where treatment approval is sought. These authorities are responsible for checking the risk/benefit ratio of their trial - their approval does not mean that the therapy is 'safe' or effective, only that a trial can be conducted.
Depending on the product type and development stage, investigators initially enrolled volunteers or patients into small pilot studies, and then conducted a larger, progressive scale comparison study. Clinical trials may vary in size and cost, and they may involve a research center or multiple centers, in one country or in several countries. The design of clinical research aims to ensure scientific validity and reproducibility of results.
The cost for clinical trials can reach billions of dollars per approved drug. Sponsors may be government organizations or pharmaceutical companies, biotechnology, or medical devices. Certain functions required for the experiment, such as monitoring and practicum, may be managed by an outsourced partner, such as a contract research organization or a central laboratory.
Only 10 percent of all drugs initiated in human clinical trials become approved drugs.
Video Clinical trial
Overview
Drug trial
Some clinical trials involve healthy subjects without pre-existing medical conditions. Other clinical trials are associated with patients with certain health conditions who are willing to try experimental treatments.
When participants are healthy volunteers who receive financial incentives, the goals are different from when the participants are sick. During the dosing period, research subjects usually remain under supervision for one to 40 nights.
Usually pilot experiments are conducted to gain insights for clinical trial design to follow.
There are two goals for testing medical care: to find out if they work well enough, called "efficacy" or "effectiveness"; and to find out if they are safe enough, called "safety". There are no absolute criteria; both safety and efficacy are evaluated relative to how treatment is intended to be used, what other treatments are available, and the severity of the disease or condition. The benefits must outweigh the risks. For example, many drugs to treat cancer have serious side effects that would not be acceptable for over-the-counter pain medications, but cancer drugs have been approved because they are used under the care of doctors, and are used for life-threatening conditions.
In the US, the elderly account for 14% of the population, while they consume more than a third of the drug. People over the age of 55 (or the same age) are often excluded from the trial because of greater health problems and drug use complicates data interpretation, and because they have different physiological capacities than younger people. Children and people with unrelated medical conditions are also often excluded. Pregnant women are often excluded because of the potential risks to the fetus.
Sponsors design trials in coordination with a panel of expert clinical investigators, including alternative or existing treatments to compare with new drugs and what types of patients might benefit. If the sponsor can not obtain enough test subjects in one location, researchers at other locations are recruited to join the study.
During the trial, researchers recruited subjects with predetermined characteristics, administered care and collected data on the subject's health for a prescribed period of time. Data include measurements such as vital signs, study drug concentrations in the blood or tissues, changes in symptoms, and whether the correction or deterioration of the conditions targeted by the study drug occurred. The researchers sent data to the trial sponsor, who then analyzed the data collected using statistical tests.
Examples of clinical trial objectives include assessing the safety and relative effectiveness of drugs or devices:
- In certain types of patients, for example, patients who have been diagnosed with Alzheimer's disease
- At various doses, for example, a dose of 10 milligrams rather than a 5 milligram dose
- For new indications
- Evaluation for improved efficacy in treating the patient's condition compared to standard therapy for the condition
- Evaluation of a drug or research device relative to two or more approved interventions for that condition, eg device A versus device B, or therapy A versus therapy B)
While most clinical trials tested one new intervention alternative, some expanded to three or four and may include placebo.
Except for small trials, a single location, design and purpose are set in a document called a clinical trial protocol. The protocols are "operating manuals" of trials and ensure that all investigators experiment in the same way on the same subject and that data can be compared across subjects.
While trials are designed to test hypotheses and strictly monitor and assess results, this can be seen as the application of the scientific method, in particular the experimental step.
The most common clinical trials evaluate new pharmaceutical products, medical devices (such as new catheters), biology, psychological therapy, or other interventions. Clinical trials may be required before the national regulatory body approves the marketing of innovation.
Device trial
Similarly for pharmaceuticals, medical equipment manufacturers in the United States are required to conduct clinical trials for premarket approval. Device trials can compare new devices with established therapies, or can compare devices that are similar to each other. An example of a former in vascular surgery is OpenVus versus Endovascular (OVER trial) for the treatment of aortic aneurysm of the stomach, which compares older longitudinal aortic repair techniques to newer endovascular aneurysm repairs. The latter example is a clinical trial of a mechanical device used in the management of women's urine incontinence.
Trial procedure
Similarly, drugs, medical or surgical procedures may be subject to clinical trials, such as controlled case studies for surgical intervention.
Maps Clinical trial
History
The concept behind ancient clinical trials. The Book of Daniel chapter 1, verses 12 through 15, for example, describes a well-planned experiment of early observation and follow-up of two groups who took part, or did not partake of the "King's meat" during the trial period. ten days. The Persian physician Avicenna, in The Canon of Medicine (1025) provides similar suggestions for determining the efficacy of drugs and medical substances.
Development
Although preliminary medical trials are often conducted, the use of control groups to provide an accurate comparison to the demonstration of the efficacy of interventions, is generally less. For example, Lady Mary Wortley Montagu, who campaigned for the introduction of inoculation (called variolation) to prevent smallpox, arranged for seven prisoners who had been sentenced to death to undergo vikolarization in exchange for their lives. Although they survived and did not have smallpox, there was no control group to assess whether these results were due to inoculation or some other factor. Similar experiments conducted by Edward Jenner on his smallpox vaccine are both conceptually defective.
The first proper clinical trial was conducted by doctor James Lind. Scurvy, now known to be caused by vitamin C deficiency, often has a detrimental effect on the welfare of long-distance ocean crew crew. In 1740, the disastrous results of traveling around Anson drew much attention in Europe; of 1900 men, 1400 have died, most of them allegedly suffering from scurvy. John Woodall, a British military surgeon from the British East India Company, has recommended consumption of citrus fruits (he had antiscorbutic effects) from the 17th century, but their use is not widespread.
Lind conducted a systematic first clinical trial in 1747. She included an acid-quality dietary supplement in an experiment after two months at sea, when the ship had already suffered from scurvy. He divided twelve scapeless sailors into six groups of two. They all received the same diet but, in addition, group one was given a liter of apple cider every day, a group of two twenty-five drops of elixir vitriol (sulfuric acid), a group of three six spoons of vinegar, a group of four and a half pints of seawater, a group of five received two oranges and one lemon, and the last group of spicy pasta plus a glass of water barley. The five group treatments stopped after six days when they ran out of fruit, but at that time one sailor was fit for duty while the other almost recovered. In addition, only one group also showed some effects of its treatment.
After 1750 the discipline began to take its modern form. John Haygarth demonstrated the importance of the control group for the correct identification of the placebo effect in his famous study of an ineffective drug called the Perkin Tractor . Further work in that direction was carried out by leading physician Sir William Gull, 1st Baronet in the 1860s.
Frederick Akbar Mahomed (died 1884), who works at Guy's Hospital in London, contributes substantially to the clinical trial process, where "he separates chronic nephritis with secondary hypertension from what we now call essential hypertension." He also founded Collective Investigations. Record for the British Medical Association, the organization collects data from physicians who practice outside hospital settings and are the forerunner of modern collaborative clinical trials. "
Modern trials
Sir Ronald A. Fisher, while working for Rothamsted's experimental station in agriculture, developed his experimental design principles in 1920 as an accurate methodology for the proper design of experiments. Among his main ideas, is the importance of randomly assigning individuals to various groups for experiments; replication - to reduce uncertainty, measurements must be repeated and replicated experiments to identify sources of variation; blocking - to organize the experimental units into groups of units that are similar to each other, and thus reduce the source of irrelevant variations; the use of factorial experiments - is efficient in evaluating the effects and possible interactions of several independent factors.
The UK Medical Research Council officially recognized the importance of clinical trials from the 1930s. The Board established the Therapy Exam Committee to advise and assist in properly controlled clinical trial setting on new products that appear to be on experimental grounds of value in the treatment of disease.
The first randomized curative trial was conducted at the MRC Tuberculosis Research Unit by Sir Geoffrey Marshall (1887-1982). The trial, conducted between 1946-1947, aims to test the efficacy of chemical streptomycin to cure pulmonary tuberculosis. The trial was double-blind and placebo-controlled.
The clinical trial methodology was further developed by Sir Austin Bradford Hill, who has been involved in the streptomycin test. From the 1920s, Hill applied statistics for medicine, attending famous mathematician Karl Pearson's lectures, among others. He became famous for an important study conducted in collaboration with Richard Doll on the correlation between smoking and lung cancer. They conducted a case-control study in 1950, which compared lung cancer patients with matched controls and also started a sustainable long-term prospective study into the wider smoking and health issues, which involved studying the smoking and health habits of more than 30,000 physicians. for several years. His certificate for the election of the Royal Society called him "... a leader in development in experimental method medicine right now used nationally and internationally in the evaluation of new therapeutic and prophylactic agents."
International clinical trial day is celebrated on May 20th.
Type
One way to classify clinical trials is by the way the researchers behave.
- In an observational study, researchers observed the subject and measured their results. The researchers did not actively manage the research.
- In an intervention study, the investigators provided subjects of specific drug research or other interventions to compare treated subjects with those who did not receive standard care or treatment. Then the researchers measured how the subject health changes.
Another way to classify trials is with their goals. The US National Institutes of Health (NIH) conducts trials into five types:
- Prevention trials look for better ways to prevent illness in people who have never had the disease or to prevent disease return. This approach may include medicines, vitamins, vaccines, or lifestyle changes.
- The screening trial tests the best way to detect a particular disease or health condition.
- Diagnostic trials are performed to find better tests or procedures for diagnosing certain diseases or conditions.
- The treatment trial tests an experimental treatment, a new drug combination, or a new approach to surgery or radiation therapy.
- Life quality trials (supportive care trials) look for ways to improve the comfort and quality of life of individuals with chronic illness.
- Compassionate use trials or expanded access trials provide partially tested, unapproved therapies to a small number of patients who have no other realistic options. Typically, this involves a disease for which no effective therapy has been approved, or a patient who has failed all standard care and whose health is too compromised to qualify for participation in randomized clinical trials. Normally, case-by-case approval should be provided by the United States Food and Drug Administration and pharmaceutical companies for the exemption.
The third classification is whether the experimental design allows for changes based on data accumulation during the trial.
- The test still considers existing data only during the test design, do not change the experiment after it starts and do not rate the results until the research is completed.
- Adaptive clinical tests use existing data to design trials, and then use temporary results to modify the trial as a result. Modifications include dose, sample size, drug trial, patient selection criteria and a mixture of "cocktails". Adaptive tests often use Bayesian experimental design to assess the progress of the trial. In some cases, trials have become an ongoing process that regularly adds and reduces therapy and patient groups as more information is gained. The goal is to more quickly identify drugs that have a therapeutic effect and target the patient population for whom the drug is appropriate.
Finally, a common way to distinguish trials is by phase, which in simple terms, relates to how closely the drug is clinically proven, both effective for the purposes stated and accepted by regulatory authorities to be used for that purpose.
Phase
Clinical trials involving new drugs are usually classified into five phases. Each phase of the drug approval process is treated as a separate clinical trial. The process of drug development will usually run through the four phases over the years. If the drug passes through phases 1, 2, and 3, it will normally be approved by a national regulatory authority for use in the general population. Before pharmaceutical companies begin clinical trials on drugs, they will also conduct extensive preclinical studies. Each phase has a different purpose and helps scientists answer different questions.
Trial design
The fundamental difference in evidence-based practice is between observational studies and randomized controlled trials. The types of observational studies in epidemiology, such as cohort studies and case-control studies, provide less convincing evidence than randomized controlled trials. In the observational study, the researchers retrospectively assessed the relationship between treatment given to participants and their health status, with potential errors in design and interpretation.
Randomized controlled trials can provide compelling evidence that research treatment has an effect on human health.
Currently, several phases 2 and the most phase 3 pharmaceutical trials are designed as random, double-blind, and placebo-controlled.
- Random: Each study subject was randomly assigned to receive study or placebo treatment.
- Blind: The subjects involved in the study did not know which study treatment they were receiving. If the study is double blind, researchers also do not know which treatment the subjects receive. This intention is to prevent researchers from treating the two groups differently. A form of double-blind study called "double-dummy" design allows additional insurance against bias. In this study, all patients were given placebo and active doses in alternating periods.
- Placebo-controlled: The use of placebo (the treatment of false) allows researchers to isolate the effect of study treatment from the placebo effect.
Clinical studies have a small number of subjects may be "sponsored" by a single researcher or a small group of researchers, and are designed to test simple or feasible questions to extend research for a more randomized, controlled, controlled trial.
Active control study
In many cases, giving a placebo to someone suffering from a disease may be unethical. To overcome this, it has become common practice to perform "active comparators" (also known as "active control") experiments. In trials with an active control group, subjects were given either an experimental treatment or a previously approved treatment with known effectiveness.
Parent protocol
In the study, some experimental treatments were tested in a single experiment. Genetic testing allows researchers to group patients according to their genetic profile, giving the drug based on that profile to the group and comparing the results. Many companies can participate, each carrying different drugs. The first such approach targets squamous cell cancer, which includes a variety of genetic disorders from patient to patient. Amgen, AstraZeneca and Pfizer are involved, the first time they work together in the final-stage trials. Patients whose genomic profiles do not match with one of the drug-receiving drugs are designed to stimulate the immune system to attack the cancer.
Clinical trial protocol
Clinical trial protocol is the document used to define and manage the trial. This is prepared by an expert panel. All study researchers are expected to closely observe the protocol.
This Protocol explains the scientific reasons, objectives (s), design, methodology, statistical considerations and the organization of the planned hearing. Trial details are provided in the documents referenced in the protocol, such as an investigator's brochure.
This protocol contains an appropriate study plan to ensure the safety and health of the trial subjects and to provide appropriate templates for experiments by researchers. This allows data to be aggregated across all investigators/sites. The protocol also notifies the study administrators (often contract research organizations).
The format and content of clinical trial protocols sponsored by pharmaceutical, biotech or medical devices in the United States, European Union or Japan has been standardized to follow the Good Clinical Practice guidelines issued by the International Conference on Harmonization of the Technical Requirements for Pharmaceutical Registration for Human Use ICH). Regulatory authorities in Canada and Australia also follow ICH guidelines. Journals like Exam , encourage researchers to publicize their protocols.
Design features
Informed consent
Clinical trials recruited research subjects to sign documents representing their "informed consent". This document includes details such as objectives, duration, required procedures, risks, potential benefits, key contacts and institutional requirements. Participants then decide whether to sign the document. This document is not a contract, because participants can withdraw at any time without penalty.
Informed consent is a legal process in which recruits are instructed on key facts before deciding whether to participate. Researchers explain the details of the research in terms of the subject can understand. The information is presented in the original language of the subject. Generally, children can not autonomously provide informed consent, but depending on age and other factors, it may be necessary to give consent.
Strength stats
The number of subjects has a major impact on the ability to reliably detect and measure the effects of the intervention. This is described as his "power". The larger the number of participants, the greater the statistical power and the greater the cost.
Statistical strength estimates the ability of an experiment to detect a certain size difference (or greater) between the treatment group and the control group. For example, trials of lipid versus placebo with 100 patients in each group may have a strength of 0.90 to detect differences between the placebo group and the test group receiving a dose of 10 mg/dL or more, but only 0.70 to detect a difference of 6 mg/dL.
Placebo Group
Only giving care can have a nonspecific effect. This is controlled by the inclusion of patients receiving only placebo. Subjects are assigned randomly without telling them which group they are from. Many experiments are so blinded that researchers do not know which group the subject is assigned to.
Assigning a subject to a placebo group may pose an ethical problem if it violates its right to receive the best available treatment. The Helsinki Declaration provides guidance on this issue.
Duration
Clinical trials are only a small part of the research that goes into the development of new treatments. Potential drugs, for example, must first be found, refined, characterized, and tested in the laboratory (in cell and animal studies) before ever undergoing clinical trials. Overall, about 1,000 potential drugs were tested before only one reached the point tested in clinical trials. For example, a new cancer drug, on average, had research for six years before it even made it into a clinical trial. But the great deprivation in making new cancer drugs available is the time it takes to complete the clinical trials themselves. On average, about eight years elapsed from the time the cancer drug entered clinical trials until receiving approval from regulatory agencies for sale to the public. Drugs for other diseases have the same timeline.
Some of the reasons for clinical trials may take several years:
- For chronic conditions such as cancer, it takes months, if not years, to see if cancer treatment has an effect on the patient.
- For unexpected drugs have a strong effect (meaning a large number of patients must be recruited to observe any 'effect'), recruiting enough patients to test the effectiveness of the drug (ie, obtaining statistical power) can take several years.
- Only certain people who have target disease conditions are eligible to take part in any clinical trials. Researchers who treat this particular patient should participate in the trial. Then they have to identify the patients they want and get approval from them or their families to take part in the trial.
The biggest obstacle to completing the study is the shortage of people taking part. All drugs and many device trials target a subset of the population, which means not everyone can participate. Some drug trials require patients to have a combination of unusual disease characteristics. It is a challenge to find the right patient and get their approval, especially when they may not receive direct benefits (because they are not paid, research drugs have not been proven to work, or patients may receive placebo). In the case of cancer patients, less than 5% of adults with cancer will participate in drug trials. According to the American Pharmaceutical and Producer Research (PhRMA), about 400 cancer drugs are being tested in clinical trials in 2005. Not all of these will prove useful, but those who may be delayed in getting approved because the number of participants is very low.
For clinical trials involving the potential for seasonal influences (such as airborne allergies, seasonal affective disorders, influenza, and skin diseases), this study may be conducted during a limited part of the year (such as spring for pollen allergy), when the drug can be tested.
Clinical trials that do not involve new drugs usually have a much shorter duration. (Exceptions are epidemiological studies, such as the Nurses' Health Study).
Administration
Clinical trials designed by local investigators, and (in the US) funded by federal clinical trials, are almost always managed by researchers who design research and apply for grants. Small scale device research can be done by the sponsoring company. Clinical trials of new drugs are usually administered by contract research organizations (CROs) hired by sponsoring companies. The sponsor provides medicine and medical supervision. CROs are contracted to perform all administrative work on clinical trials. For phases 2, 3, and 4, CRO recruits participating researchers, trains them, provides them with supplies, coordinates the administration of studies and data collection, arranges meetings, monitors sites for compliance with clinical protocols, and ensures the sponsor receives data from each site. Special location management organizations can also be hired to coordinate with CROs to ensure quicker IRB/IEC approval and faster site initiation and patient recruitment. Phase 1 clinical trials of new drugs are often performed in specialist clinical trials clinics, with specialized pharmacologists, in which subjects can be observed by full-time staff. These clinics are often run by CRO specializing in this study.
On participating sites, one or more research assistants (often nurses) do most of the work in conducting clinical trials. The work of a research assistant may include some or all of the following: provide local institutional review board (IRB) with the documentation required to obtain permission to undertake research, help initiate studies, identify qualified patients, obtain consent from them or their families, study, collect and analyze data statistically, maintain and update data files during follow-up, and communicate with IRB, as well as sponsors and CROs.
Marketing
Janet Yang uses the Interactional Justice Model to test the effect of willingness to talk to doctors and clinical trial enrollment. The results found that potential clinical trial candidates were less likely to enroll in clinical trials if patients were more willing to talk to their physician. The reasoning behind this discovery may be that patients are happy with their current care. Another reason for the negative relationship between perceived fairness and clinical trial registration is the lack of independence of the care providers. The results found that there was a positive relationship between lack of willingness to talk to their doctors and clinical trial enrollment. A lack of willingness to talk about clinical trials with current care providers may be due to the patient's independence from the doctor. Patients less likely to talk about clinical trials are more willing to use other sources of information to gain better insight into alternative treatments. Registration of clinical trials should be motivated to utilize websites and television advertisements to inform the public of clinical trial enrollment.
Information technology
The last decade has seen the proliferation of the use of information technology in the planning and execution of clinical trials. Clinical trial management systems are often used by research sponsors or CROs to help plan and manage the operational aspects of clinical trials, particularly with regard to site investigations. Further analysis to identify researchers and research sites with expertise in a particular field utilizing public and private information about ongoing research. Web-based electronic data retrieval (EDC) and clinical data management systems are used in most clinical trials to collect case report data from the site, manage its quality, and prepare it for analysis. An interactive voice response system is used by the site to register patient registration using the phone and allocate the patient to a particular treatment arm (though the phone is increasingly replaced by a web-based tool (IWRS) which is sometimes part of the EDC system). Although patient reported results are often paper-based in the past, measurements are increasingly collected using web portals or ePRO (or eDiary) handheld devices, sometimes wirelessly. Statistical software is used to analyze the data collected and prepare them for the submission of the rules. Access to many of these applications is increasingly aggregated in web-based clinical trial portals. In 2011, the FDA approved a Phase 1 trial using telemonitoring, also known as remote patient monitoring, to collect biometric data in a patient's home and send it electronically to a trial database. This technology provides more data points and is much more convenient for patients, as they have fewer visits to experiment sites.
Ethical Aspects
Clinical trials are closely monitored by appropriate regulatory authorities. All studies involving medical or therapeutic interventions in patients should be approved by the supervisory ethics committee before permission is given to run the trial. The local ethics committee has a policy on how it will oversee noninterventional studies (observational studies or those using data already collected). In the US, this body is called the Institutional Review Board (IRB); in the European Union, they are called Ethics committees. Most IRBs are located in local hospitals or research institutions, but some sponsors allow the use of central IRBs (independent/for profit) for investigators working in smaller institutions.
To be ethical, the researcher should obtain full and informed consent from participating human subjects. (One of the main functions of the IRB is to ensure that potential patients are well informed about clinical trials.) If the patient can not approve of himself, the researcher may seek approval from the authorized legal representative of the patient. In California, the state has prioritized individuals who can serve as legitimate representatives.
In some US locations, local IRBs should certify their researchers and staff before they can conduct clinical trials. They must understand the federal patient's privacy laws (HIPAA) and good clinical practice. The International Conference of Harmonization Guidelines for Good Clinical Practice is a set of internationally used standards for clinical trials. These guidelines aim to ensure "rights, safety and welfare of trial subjects are protected".
The idea of ​​informed consent from participating human subjects is in many countries around the world, but the exact definition may still vary.
Informed consent is clearly a 'necessary' condition for ethical behavior but does not 'ensure' ethical behavior. In a loving trial, the latter becomes a very difficult problem. The ultimate goal is to serve the patient or patient community of the future in the best and responsible way. See also Extended access. However, it may be difficult to turn this goal into a clear, quantifiable objective function. In some cases this can be done, for example, for questions about when to stop sequential treatment (see Odds algorithm), and then quantified methods can play an important role.
Additional ethical issues are present when conducting clinical trials in children (pediatrics), and in emergency or epidemic situations.
Unfavorable conflict of interest and study
In response to certain cases where unfavorable data from research-sponsored pharmaceutical companies were not published, the American Pharmaceutical and Producer Research published new guidelines urging companies to report all findings and restrict financial involvement in drug companies by researchers. The US Congress signed a law requiring Phase II and Phase III clinical trials to be registered by sponsors on the clinicaltrials.gov website compiled by the National Institutes of Health.
Drug researchers who are not directly employed by pharmaceutical companies often seek grants from producers, and manufacturers often look to academic researchers to conduct studies within their university and hospital networks, for example, for translational cancer research. Similarly, competition for tenured academic positions, government grants and prestige creates conflicts of interest among academic scientists. According to one study, about 75% of the articles were withdrawn for reasons related to errors not having the industry's stated financial support. The nesting test is highly controversial.
In the United States, all clinical trials submitted to the FDA as part of the drug approval process are independently assessed by clinical experts in the Food and Drug Administration, including primary data collection inspections at selected clinical trials sites.
In 2001, editors from 12 major journals published a joint editorial, published in each journal, on control over clinical trials provided by sponsors, primarily targeting the use of contracts that allowed sponsors to review studies prior to publication and holding publications. They reinforce editorial restrictions to counteract its effects. The editorial notes that the contract research organization, in 2000, received 60% of grants from pharmaceutical companies in the US. Researchers can be limited from contributing to the experiment design, accessing raw data, and interpreting the results.
Security
The responsibility for the safety of the subject in clinical trials is shared between sponsors, investigators of local sites (if different from sponsors), various IRBs who oversee the research, and (in some cases, if research involves marketable drugs) or devices ), regulatory bodies for countries where drugs or devices will be sold.
For safety reasons, many drug clinical trials are designed to exclude women of childbearing age, pregnant women, or pregnant women during the study. In some cases, the male partner of this woman is also excluded or asked to take birth control measures.
Sponsor
During clinical trials, the sponsor is responsible for accurately telling investigators the local location of the actual historical safety record of any medications, tools or other medical treatments to be tested, and any potential interactions of approved study care care. This allows local researchers to make judgments about whether to participate in the study or not. Sponsors are also responsible for monitoring research results as they come from various sites during the trial. In larger clinical trials, sponsors will use the services of the data monitoring committee (DMC, known in the US as a data security monitoring council). This group of doctors and independent statisticians meets regularly to review the irrefutable data that the sponsor has received so far. DMCs have the power to recommend discontinuation of studies based on their reviews, for example if study care leads to more deaths than standard treatment, or appears to cause unexpected and associated adverse events. The sponsor is responsible for collecting adverse event reports from all site researchers in the study, and to inform all investigators of the sponsor's assessment of whether these side-effects are related or unrelated to the research care.
Sponsors and local site investigators are jointly responsible for writing informed consent based on locations that accurately inform potential subjects about the risks and potential benefits of participating in the research while at the same time presenting the material as briefly as possible and in everyday language. FDA regulations state that participating in clinical trials is voluntary, with subjects having the right not to participate or to terminate participation at any time.
Local site researcher
The primal non-nocere ethical principle ("first, no harm") guides the trial, and if an investigator believes that research treatment may harm the subject in the study, the investigator may stop participating at the time. On the other hand, researchers often have a financial interest in recruiting subjects, and can act unethically to gain and retain their participation.
Local researchers are responsible for conducting research in accordance with the study protocol, and overseeing the study staff during the study period. The local researcher or his study staff is also responsible for ensuring the potential subjects in this study understand the potential risks and benefits of participating in the study. In other words, they (or their authorized representatives) must provide informed consent.
Local researchers are responsible for reviewing all reports of adverse events sent by sponsors. Reports of these adverse events contain opinions from both investigators on sites where adverse events occur, and sponsors, regarding the relationship of adverse events with study care. The local researcher is also responsible for making independent assessments of this report, and immediately notifies the local IRB of all seriousness and studies of medication-related adverse events.
When local investigators are sponsors, there may be no official harmful event report, but the study staff at all locations are responsible for informing the coordinator's investigator of unexpected matters. Local investigators are responsible for being honest to the local IRB in all research-related communications.
Institutional review boards (IRBs)
Approval by the Institutional Review Board (IRB), or ethics board, is required before all but the most informal research can begin. In commercial clinical trials, the study protocol was not approved by IRB before the sponsor recruited the site to conduct trials. However, the study protocols and procedures have been adjusted to conform to the generic IRB delivery requirements. In this case, and where there are no independent sponsors, each investigator of the local site submits a research protocol, approval (s), data collection form, and supporting documentation to the local IRB. Universities and most hospitals have internal IRBs. Other researchers (such as at the clinic) use independent IRB.
IRB researched research for the medical safety and patient protection involved in the research, before allowing researchers to begin the study. This may require a change in the study procedure or in the explanation given to the patient. The "annual review" annual report requested from the investigator will update IRB on the progress of the study and all new safety information related to the research.
Regulatory Bureau
In the US, the FDA may audit investigator files of local sites after they have participated in the study, to see if they are properly following the research procedure. This audit may be random, or for reasons (because investigators are suspected of being fraudulent data). Avoiding audits is an incentive for researchers to follow the study procedure.
Alternatively, many American pharmaceutical companies have transferred several clinical trials abroad. The benefits of conducting trials abroad include lower costs (in some countries) and the ability to run larger trials in a shorter time period, while potential losses are in low quality experimental management. Different countries have different regulatory requirements and enforcement capabilities. An estimated 40% of all clinical trials now occur in Asia, Eastern Europe, and Central and South America. "There is no mandatory registration system for clinical trials in these countries and many do not follow European directives in their operations," said Jacob Sijtsma of the Netherlands-based WEMOS, an advocacy health organization that tracks clinical trials in developing countries.
Beginning in the 1980s, the harmonization of clinical trial protocols proved feasible in EU countries. At the same time, coordination between Europe, Japan and the United States leads to a joint-industry joint initiative on international harmonization named after 1990 as the International Conference on Harmonization of Technical Requirements for Pharmaceutical Registration for Human Use (ICH) Currently, most test programs Clinical follow the ICH guidelines, which aims to "ensure that good quality, safe and effective drugs are developed and registered in the most efficient and cost-effective way.These activities are conducted for the benefit of consumers and public health, to prevent things that are not the need for duplication of clinical trials in humans and to minimize the use of animal testing without compromising the obligations of security arrangements and effectiveness. "
Security data aggregation during clinical development
Combining safety data across clinical trials during drug development is important because trials are generally designed to focus on determining how well the drug works. Security data was collected and collected in several trials because the drug was developed to allow sponsors, investigators and regulatory agencies to monitor the aggregate safety profile of experimental drugs as they were developed. The value of assessment of aggregate security data is: a) decisions based on an aggregate security assessment during drug development can be performed throughout drug development and b) establishing a good sponsorship and regulator to assess drug safety once the drug is approved.
Economy
The cost of clinical trials varies depending on the experimental phase, the type of experiment, and the disease under study. A clinical trial study conducted in the United States from 2004 to 2012 found the average cost of a phase I trial to $ 1.4 million and $ 6.6 million, depending on the type of disease. Phase II trials range from $ 7 million to $ 20 million, and a Phase III trial of $ 11 million to $ 53 million.
Sponsor
The cost of the study depends on many factors, especially the number of sites conducting the study, the number of patients involved, and whether the study care has been approved for medical use.
Costs incurred by pharmaceutical companies in managing phase 3 or 4 clinical trials may include, among others:
- the production of the drug or device being evaluated
- staff salaries for designers and trial administrators
- payments to a contract research organization, a site management organization (if used) and any outside consultant
- payment to local researchers and their staff for their time and effort in recruiting test subjects and collecting data for sponsors
- the cost of study materials and the costs incurred to submit it
- communication with local researchers, including on-site monitoring by CRO before and (in some cases) several times during the research
- one or more investigator training sessions â € <â € <
- costs incurred by local researchers, such as pharmaceutical fees, IRB fees and postage
- any payment to the subject listed in the trial
- the cost of treating a test subject that develops a medical condition caused by a study drug
These costs occur for several years.
In the US, sponsors may receive 50 percent tax credits for clinical trials conducted on drugs developed for the treatment of orphan disease. National health agencies, such as the US National Institutes of Health, offer grants to researchers who design clinical trials that try to answer research questions of interest to the institution. In this case, the investigator â € <â €
Researchers are often compensated for their work in clinical trials. This amount may be small, covering only a fraction of salary for research assistants and any inventory costs (usually with the study of national health agencies), or substantial and including 'overhead' which allows investigators to pay research staff during the time between clinical trials.
Subject
Participants in Phase 1 drug trials did not get direct health benefits from taking part. They generally pay a fee for their time, with payment arranged and not associated with any risk involved. In the next phase of testing, subjects may not be paid to ensure their motivation to participate with potential health benefits or contribute to medical knowledge. Small payments can be made for fees related to studies such as travel or as compensation for their time in providing follow-up information about their health after the trial treatment is over.
Recruitment and participation of participants
Phase 0 and Phase 1 drug trials are looking for healthy volunteers. Most other clinical trials look for patients who have certain disease or medical conditions. The diversity observed in the community should be reflected in clinical trials through appropriate inclusion of ethnic minority populations. Recruitment of patients or recruitment of participants plays an important role in the activities and responsibilities of sites conducting clinical trials.
All volunteers considered for testing are required to perform a medical examination. Requirements differ according to the needs of the trial, but usually volunteers will be screened in medical laboratories to:
- Measurement of heart electrical activity (ECG)
- Measurement of blood pressure, heart rate and body temperature
- Blood sampling
- Urine sampling
- Height and height measurement
- Drug abuse test
- Pregnancy test
Finding an experiment
Depending on the type of participants required, clinical trial sponsors, or contract research organizations working on their behalf, try to find sites with qualified personnel and access to patients who can participate in the trial. Working with these sites, they can employ various recruitment strategies, including patient databases, newspaper and radio advertisements, leaflets, posters in places where patients may visit (such as doctor's offices), and personal recruitment of patients by researchers.
Volunteers with certain conditions or diseases have additional online resources to help them find clinical trials. For example, Fox Trial Finder connects Parkinson's Park trials worldwide to volunteers who have specific criteria such as location, age, and symptoms. Other disease-specific services exist for volunteers to find trials related to their condition. Volunteers can search directly at ClinicalTrials.gov to find trials using a registry run by the US National Institutes of Health and the National Library of Medicine.
Research
The risk retrieval and information processing model (RISP) analyzes the social implications that influence attitudes and decision-making related to clinical trials. People who have a higher stake or interest in care provided in clinical trials suggest a greater likelihood of seeking information about clinical trials. Cancer patients report a more optimistic attitude toward clinical trials than the general population. Having a more optimistic view on clinical trials also leads to greater registration possibilities.
References
Further reading
External links
- International Conference on Harmonization of Technical Requirements for Pharmaceutical Registration for Human Use (ICH)
- ClinicalTrials.gov
- Clinical test for cancer research - National Cancer Institute
Source of the article : Wikipedia
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