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62-1251: The MTN's notable research included various clinical trials . The results of the CAPRISA 004 trial inspired the research of the MTN and the microbicide field. The Vaginal and Oral Interventions to Control the Epidemic (VOICE) found a vaginal gel containing an anti-HIV drug to be ineffective at preventing HIV transmission.. The HOPE study tested dapivirine vaginal rings for HIV prevention in 1,456 study participants at 14 sites in Malawi, South Africa, Uganda and Zimbabwe. Clinical trials Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines , drugs , dietary choices , dietary supplements , and medical devices ) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in

124-404: A stethoscope . The pulse may vary due to exercise, fitness level, disease, emotions, and medications. The pulse also varies with age. A newborn can have a heart rate of 100–⁠160 bpm, an infant (0–⁠5 months old) a heart rate of 90–⁠150 bpm, and a toddler (6–⁠12 months old) a heart rate of 80–140 bpm. A child aged 1–⁠3 years old can have a heart rate of 80–⁠130 bpm, a child aged 3–⁠5 years old

186-506: A column of mercury measured off in millimeters . In the United States and UK, the common form is millimeters of mercury, while elsewhere SI units of pressure are used. There is no natural 'normal' value for blood pressure, but rather a range of values that on increasing are associated with increased risks. The guideline acceptable reading also takes into account other co-factors for disease. Therefore, elevated blood pressure ( hypertension )

248-415: A dietary supplement of an acidic quality in the experiment after two months at sea, when the ship was already afflicted with scurvy. He divided twelve scorbutic sailors into six groups of two. They all received the same diet but, in addition, group one was given a quart of cider daily, group two twenty-five drops of elixir of vitriol ( sulfuric acid ), group three six spoonfuls of vinegar , group four half

310-461: A different purpose to construct focus on identifying a specific effect. Clinical trials involving new drugs are commonly classified into five phases. Each phase of the drug approval process is treated as a separate clinical trial. The drug development process will normally proceed through phases I–IV over many years, frequently involving a decade or longer. If the drug successfully passes through phases I, II, and III, it will usually be approved by

372-466: A heart rate of 80–⁠120 bpm, an older child (age of 6–10) a heart rate of 70–⁠110 bpm, and an adolescent (age 11–⁠14) a heart rate of 60–105 bpm. An adult (age 15+) can have a heart rate of 60–100 bpm. Average respiratory rates vary between ages, but the normal reference range for people age 18 to 65 is 16–20 breaths per minute. The value of respiratory rate as an indicator of potential respiratory dysfunction has been investigated but findings suggest it

434-419: A landmark study carried out in collaboration with Richard Doll on the correlation between smoking and lung cancer . They carried out a case-control study in 1950, which compared lung cancer patients with matched control and also began a sustained long-term prospective study into the broader issue of smoking and health, which involved studying the smoking habits and health of more than 30,000 doctors over

496-490: A national regulatory authority approves marketing of the innovation. Similarly to drugs, manufacturers of medical devices in the United States are required to conduct clinical trials for premarket approval . Device trials may compare a new device to an established therapy, or may compare similar devices to each other. An example of the former in the field of vascular surgery is the Open versus Endovascular Repair (OVER trial) for

558-434: A panel of expert clinical investigators, including what alternative or existing treatments to compare to the new drug and what type(s) of patients might benefit. If the sponsor cannot obtain enough test subjects at one location investigators at other locations are recruited to join the study. During the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment(s) and collect data on

620-492: A period of several years. His certificate for election to the Royal Society called him "...   the leader in the development in medicine of the precise experimental methods now used nationally and internationally in the evaluation of new therapeutic and prophylactic agents ." International clinical trials day is celebrated on 20 May. The acronyms used in the titling of clinical trials are often contrived, and have been

682-456: A person's vital signs vary with age, weight, sex , and overall health . There are four primary vital signs : body temperature , blood pressure , pulse ( heart rate ), and breathing rate ( respiratory rate ), often notated as BT, BP, HR, and RR. However, depending on the clinical setting, the vital signs may include other measurements called the "fifth vital sign" or "sixth vital sign." Early warning scores have been proposed that combine

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744-465: A pint of seawater, group five received two oranges and one lemon , and the last group a spicy paste plus a drink of barley water . The treatment of group five stopped after six days when they ran out of fruit, but by then one sailor was fit for duty while the other had almost recovered. Apart from that, only group one also showed some effect of its treatment. Each year, May 20 is celebrated as Clinical Trials Day in honor of Lind's research. After 1750

806-412: A placebo to a person suffering from a disease may be unethical, "active comparator" (also known as "active control") trials may be conducted instead. In trials with an active control group, subjects are given either the experimental treatment or a previously approved treatment with known effectiveness. In other cases, sponsors may conduct an active comparator trial to establish an efficacy claim relative to

868-773: A role in clinical trials. While working for the Rothamsted experimental station in the field of agriculture, Fisher developed his Principles of experimental design in the 1920s as an accurate methodology for the proper design of experiments. Among his major ideas include the importance of randomization —the random assignment of individuals to different groups for the experiment; replication —to reduce uncertainty , measurements should be repeated and experiments replicated to identify sources of variation; blocking —to arrange experimental units into groups of units that are similar to each other, and thus reducing irrelevant sources of variation; use of factorial experiments —efficient at evaluating

930-420: A similar cutoff age) are often excluded from trials because their greater health issues and drug use complicate data interpretation, and because they have different physiological capacity than younger people. Children and people with unrelated medical conditions are also frequently excluded. Pregnant women are often excluded due to potential risks to the fetus . The sponsor designs the trial in coordination with

992-540: A single disease entering and leaving the platform), and basket trial (one medical product for multiple diseases or disease subtypes). Genetic testing enables researchers to group patients according to their genetic profile, deliver drugs based on that profile to that group and compare the results. Multiple companies can participate, each bringing a different drug. The first such approach targets squamous cell cancer , which includes varying genetic disruptions from patient to patient. Amgen, AstraZeneca and Pfizer are involved,

1054-491: A single research center or multiple centers , in one country or in multiple countries. Clinical study design aims to ensure the scientific validity and reproducibility of the results. Costs for clinical trials can range into the billions of dollars per approved drug, and the complete trial process to approval may require 7–15 years. The sponsor may be a governmental organization or a pharmaceutical , biotechnology or medical-device company. Certain functions necessary to

1116-423: A treatment can have nonspecific effects. These are controlled for by the inclusion of patients who receive only a placebo. Subjects are assigned randomly without informing them to which group they belonged. Many trials are doubled-blinded so that researchers do not know to which group a subject is assigned. Assigning a subject to a placebo group can pose an ethical problem if it violates his or her right to receive

1178-410: Is a thermometer , a sphygmomanometer , and a watch . Although a pulse can be taken by hand, a stethoscope may be required for a clinician to take a patient's apical pulse. Temperature recording gives an indication of core body temperature , which is normally tightly controlled ( thermoregulation ), as it affects the rate of chemical reactions. Body temperature is maintained through a balance of

1240-550: Is considered "normal" body temperature, there is some variance between individuals. Most have a normal body temperature set point that falls within the range of 36.0 to 37.5 °C (96.8 to 99.5 °F). The main reason for checking body temperature is to solicit any signs of systemic infection or inflammation in the presence of a fever . Fever is considered temperature of 37.8 °C (100.0 °F) or above. Other causes of elevated temperature include hyperthermia , which results from unregulated heat generation or abnormalities in

1302-420: Is of limited value. Respiratory rate is a clear indicator of acidotic states, as the main function of respiration is removal of CO 2 leaving bicarbonate base in circulation. Blood pressure is recorded as two readings: a higher systolic pressure, which occurs during the maximal contraction of the heart, and the lower diastolic or resting pressure. In adults, a normal blood pressure is 120/80, with 120 being

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1364-420: Is researcher and how. PPI can improve the quality of research and make it more relevant and accessible. People with current or past experience of illness can provide a different perspective than professionals and compliment their knowledge. Through their personal knowledge they can identify research topics that are relevant and important to those living with an illness or using a service. They can also help to make

1426-428: Is the rate at which the heart beats while pumping blood through the arteries, recorded as beats per minute (bpm). It may also be called "heart rate". In addition to providing the heart rate, the pulse should also be evaluated for strength and obvious rhythm abnormalities. The pulse is commonly taken at the wrist ( radial artery ). Alternative sites include the elbow ( brachial artery ), the neck ( carotid artery ), behind

1488-490: Is variously defined when the systolic number is persistently over 140–160 mmHg. Low blood pressure is hypotension . Blood pressures are also taken at other portions of the extremities. These pressures are called segmental blood pressures and are used to evaluate blockage or arterial occlusion in a limb (see Ankle brachial pressure index ). In the U.S., in addition to the above four, many providers are required or encouraged by government technology-in-medicine laws to record

1550-547: The Therapeutic Trials Committee to advise and assist in the arrangement of properly controlled clinical trials on new products that seem likely on experimental grounds to have value in the treatment of disease. The first randomised curative trial was carried out at the MRC Tuberculosis Research Unit by Sir Geoffrey Marshall (1887–1982). The trial, carried out between 1946 and 1947, aimed to test

1612-409: The cohort study and the case-control study , provide less compelling evidence than the randomized controlled trial. In observational studies, the investigators retrospectively assess associations between the treatments given to participants and their health status, with potential for considerable errors in design and interpretation. A randomized controlled trial can provide compelling evidence that

1674-463: The UK also follow ICH guidelines. Journals such as Trials , encourage investigators to publish their protocols. Clinical trials recruit study subjects to sign a document representing their " informed consent ". The document includes details such as its purpose, duration, required procedures, risks, potential benefits, key contacts and institutional requirements. The participant then decides whether to sign

1736-412: The ability of a trial to detect a difference of a particular size (or larger) between the treatment and control groups. For example, a trial of a lipid -lowering drug versus placebo with 100 patients in each group might have a power of 0.90 to detect a difference between placebo and trial groups receiving dosage of 10 mg/dL or more, but only 0.70 to detect a difference of 6 mg/dL. Merely giving

1798-454: The active comparator instead of the placebo in labeling . A master protocol includes multiple substudies, which may have different objectives and involve coordinated efforts to evaluate one or more medical products in one or more diseases or conditions within the overall study structure. Trials that could develop a master protocol include the umbrella trial (multiple medical products for a single disease), platform trial (multiple products for

1860-472: The best available treatment. The Declaration of Helsinki provides guidelines on this issue. Vital signs Vital signs (also known as vitals ) are a group of the four to six most crucial medical signs that indicate the status of the body's vital (life-sustaining) functions. These measurements are taken to help assess the general physical health of a person, give clues to possible diseases, and show progress toward recovery. The normal ranges for

1922-399: The body's heat exchange mechanisms. Temperature depression ( hypothermia ) also needs to be evaluated. Hypothermia is classified as temperature below 35 °C (95 °F). It is also recommended to review the trend of the patient's temperature over time. A fever of 38 °C does not necessarily indicate an ominous sign if the patient's previous temperature has been higher. The pulse

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1984-568: The catastrophic result of Anson 's circumnavigation attracted much attention in Europe; out of 1900 men, 1400 had died, most of them allegedly from having contracted scurvy. John Woodall , an English military surgeon of the British East India Company , had recommended the consumption of citrus fruit from the 17th century, but their use did not become widespread. Lind conducted the first systematic clinical trial in 1747. He included

2046-407: The clinical trial to follow. There are two goals to testing medical treatments: to learn whether they work well enough, called "efficacy", or "effectiveness"; and to learn whether they are safe enough, called "safety". Neither is an absolute criterion; both safety and efficacy are evaluated relative to how the treatment is intended to be used, what other treatments are available, and the severity of

2108-509: The country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies , and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, and they can involve

2170-549: The discipline began to take its modern shape. The English doctor John Haygarth demonstrated the importance of a control group for the correct identification of the placebo effect in his celebrated study of the ineffective remedy called Perkin's tractors . Further work in that direction was carried out by the eminent physician Sir William Gull, 1st Baronet in the 1860s. Frederick Akbar Mahomed (d. 1884), who worked at Guy's Hospital in London , made substantial contributions to

2232-501: The disease or condition. The benefits must outweigh the risks. For example, many drugs to treat cancer have severe side effects that would not be acceptable for an over-the-counter pain medication, yet the cancer drugs have been approved since they are used under a physician's care and are used for a life-threatening condition. In the US the elderly constitute 14% of the population, while they consume over one-third of drugs. People over 55 (or

2294-562: The document. The document is not a contract, as the participant can withdraw at any time without penalty. Informed consent is a legal process in which a recruit is instructed about key facts before deciding whether to participate. Researchers explain the details of the study in terms the subject can understand. The information is presented in the subject's native language. Generally, children cannot autonomously provide informed consent, but depending on their age and other factors, may be required to provide informed assent. In any clinical trial,

2356-412: The effects and possible interactions of several independent factors. Of these, blocking and factorial design are seldom applied in clinical trials, because the experimental units are human subjects and there is typically only one independent intervention: the treatment. The British Medical Research Council officially recognized the importance of clinical trials from the 1930s. The council established

2418-492: The efficacy of the chemical streptomycin for curing pulmonary tuberculosis . The trial was both double-blind and placebo-controlled . The methodology of clinical trials was further developed by Sir Austin Bradford Hill , who had been involved in the streptomycin trials. From the 1920s, Hill applied statistics to medicine, attending the lectures of renowned mathematician Karl Pearson , among others. He became famous for

2480-421: The first time they have worked together in a late-stage trial. Patients whose genomic profiles do not match any of the trial drugs receive a drug designed to stimulate the immune system to attack cancer. A clinical trial protocol is a document used to define and manage the trial. It is prepared by a panel of experts. All study investigators are expected to strictly observe the protocol. The protocol describes

2542-723: The heat produced by the body and the heat lost from the body. Temperature can be recorded in order to establish a baseline for the individual's normal body temperature for the site and measuring conditions. Temperature can be measured from the mouth, rectum, axilla (armpit), ear, or skin. Oral, rectal, and axillary temperature can be measured with either a glass or electronic thermometer. Note that rectal temperature measures approximately 0.5 °C higher than oral temperature, and axillary temperature approximately 0.5 °C less than oral temperature. Aural and skin temperature measurements require special devices designed to measure temperature from these locations. While 37 °C (99 °F)

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2604-423: The individual values of vital signs into a single score. This was done in recognition that deteriorating vital signs often precede cardiac arrest and/or admission to the intensive care unit . Used appropriately, a rapid response team can assess and treat a deteriorating patient and prevent adverse outcomes. There are four primary vital signs which are standard in most medical settings: The equipment needed

2666-418: The intervention's efficacy was generally lacking. For instance, Lady Mary Wortley Montagu , who campaigned for the introduction of inoculation (then called variolation) to prevent smallpox , arranged for seven prisoners who had been sentenced to death to undergo variolation in exchange for their life. Although they survived and did not contract smallpox, there was no control group to assess whether this result

2728-402: The knee ( popliteal artery ), or in the foot ( dorsalis pedis or posterior tibial arteries). The pulse is taken with the index finger and middle finger by pushing with firm yet gentle pressure at the locations described above, and counting the beats felt per 60 seconds (or per 30 seconds and multiplying by two). The pulse rate can also be measured by listening directly to the heartbeat using

2790-410: The national regulatory authority for use in the general population. Phase IV trials are performed after the newly approved drug, diagnostic or device is marketed, providing assessment about risks, benefits, or best uses. A fundamental distinction in evidence-based practice is between observational studies and randomized controlled trials . Types of observational studies in epidemiology , such as

2852-408: The number of subjects, also called the sample size, has a large impact on the ability to reliably detect and measure the effects of the intervention. This ability is described as its " power ", which must be calculated before initiating a study to figure out if the study is worth its costs. In general, a larger sample size increases the statistical power, also the cost. The statistical power estimates

2914-468: The patient's height, weight, and body mass index . In contrast to the traditional vital signs, these measurements are not useful for assessing acute changes in state because of the rate at which they change; however, they are useful for assessing the impact of prolonged illness or chronic health problems. The definition of vital signs may also vary with the setting of the assessment. Emergency medical technicians (EMTs), in particular, are taught to measure

2976-582: The process of clinical trials, where "he separated chronic nephritis with secondary hypertension from what we now term essential hypertension . He also founded the Collective Investigation Record for the British Medical Association ; this organization collected data from physicians practicing outside the hospital setting and was the precursor of modern collaborative clinical trials." Ideas of Sir Ronald A. Fisher still play

3038-407: The research more grounded in the needs of the specific communities they are part of. Public contributors can also ensure that the research is presented in plain language that is clear to the wider society and the specific groups it is most relevant for. Although early medical experimentation was performed often, the use of a control group to provide an accurate comparison for the demonstration of

3100-418: The safety and relative effectiveness of a medication or device: While most clinical trials test one alternative to the novel intervention, some expand to three or four and may include a placebo . Except for small, single-location trials, the design and objectives are specified in a document called a clinical trial protocol . The protocol is the trial's "operating manual" and ensures all researchers perform

3162-494: The scientific rationale, objective(s), design, methodology, statistical considerations and organization of the planned trial. Details of the trial are provided in documents referenced in the protocol, such as an investigator's brochure . The protocol contains a precise study plan to assure safety and health of the trial subjects and to provide an exact template for trial conduct by investigators. This allows data to be combined across all investigators/sites. The protocol also informs

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3224-550: The study administrators (often a contract research organization ). The format and content of clinical trial protocols sponsored by pharmaceutical, biotechnology or medical device companies in the United States, European Union, or Japan have been standardized to follow Good Clinical Practice guidance issued by the International Conference on Harmonisation (ICH). Regulatory authorities in Canada , China , South Korea , and

3286-832: The study treatment causes an effect on human health. Some Phase II and most Phase III drug trials are designed as randomized, double-blind , and placebo -controlled. Clinical studies having small numbers of subjects may be "sponsored" by single researchers or a small group of researchers, and are designed to test simple questions or feasibility to expand the research for a more comprehensive randomized controlled trial. Clinical studies can be "sponsored" (financed and organized) by academic institutions, pharmaceutical companies, government entities and even private groups. Trials are conducted for new drugs, biotechnology, diagnostic assays or medical devices to determine their safety and efficacy prior to being submitted for regulatory review that would determine market approval. In cases where giving

3348-456: The subject of derision. Clinical trials are classified by the research objective created by the investigators. Trials are classified by their purpose. After approval for human research is granted to the trial sponsor, the U.S. Food and Drug Administration (FDA) organizes and monitors the results of trials according to type: Clinical trials are conducted typically in four phases, with each phase using different numbers of subjects and having

3410-430: The subjects' health for a defined time period. Data include measurements such as vital signs , concentration of the study drug in the blood or tissues, changes to symptoms, and whether improvement or worsening of the condition targeted by the study drug occurs. The researchers send the data to the trial sponsor, who then analyzes the pooled data using statistical tests . Examples of clinical trial goals include assessing

3472-443: The surgical setting, case-controlled studies will be replaced. Besides being participants in a clinical trial, members of the public can be actively collaborate with researchers in designing and conducting clinical research . This is known as patient and public involvement (PPI). Public involvement involves a working partnership between patients, caregivers, people with lived experience, and researchers to shape and influence what

3534-411: The systolic and 80 being the diastolic reading. Usually, the blood pressure is read from the left arm unless there is some damage to the arm. The difference between the systolic and diastolic pressure is called the pulse pressure . The measurement of these pressures is now usually done with an aneroid or electronic sphygmomanometer . The classic measurement device is a mercury sphygmomanometer, using

3596-546: The treatment of abdominal aortic aneurysm , which compared the older open aortic repair technique to the newer endovascular aneurysm repair device. An example of the latter are clinical trials on mechanical devices used in the management of adult female urinary incontinence . Similarly to drugs, medical or surgical procedures may be subjected to clinical trials, such as comparing different surgical approaches in treatment of fibroids for subfertility . However, when clinical trials are unethical or logistically impossible in

3658-501: The trial in the same way on similar subjects and that the data is comparable across all subjects. As a trial is designed to test hypotheses and rigorously monitor and assess outcomes, it can be seen as an application of the scientific method , specifically the experimental step. The most common clinical trials evaluate new pharmaceutical products, medical devices, biologics , diagnostic assays , psychological therapies , or other interventions. Clinical trials may be required before

3720-516: The trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a contract research organization or a central laboratory. Only 10 percent of all drugs started in human clinical trials become approved drugs . Some clinical trials involve healthy subjects with no pre-existing medical conditions . Other clinical trials pertain to people with specific health conditions who are willing to try an experimental treatment. Pilot experiments are conducted to gain insights for design of

3782-639: The vital signs of respiration, pulse, skin, pupils , and blood pressure as "the 5 vital signs" in a non-hospital setting. The "fifth vital sign" may refer to a few different parameters. There is no standard "sixth vital sign"; its use is more informal and discipline-dependent. Children and infants have respiratory and heart rates that are faster than those of adults as shown in the following table : Monitoring of vital parameters most commonly includes at least blood pressure and heart rate , and preferably also pulse oximetry and respiratory rate . Multimodal monitors that simultaneously measure and display

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3844-476: Was due to the inoculation or some other factor. Similar experiments performed by Edward Jenner over his smallpox vaccine were equally conceptually flawed. The first proper clinical trial was conducted by the Scottish physician James Lind . The disease scurvy , now known to be caused by a Vitamin C deficiency, would often have terrible effects on the welfare of the crew of long-distance ocean voyages. In 1740,

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