Front cover history of clinical trials

History of Clinical Research

  • 130

    Galen of Pergumum born

    Galen of Pergumum born
    Galen was physician to the Roman emporer, Marcus Aurelius. He was one of the first individuals recorded as having performed animal studies to gain a better understanding of diseases in humans.The translation of his 129 works from Greek to Arabic by Hunayn ibn Ishaq, included a rational systematic approach to medicine, set the template for Islamic medicine. Galen of Pergumum
  • Jan 1, 1030

    Dedicated hospitals being built

    Dedicated hospitals being built
    It had been thought that dedicated hospitals were introduced to England by the Normans following the invasion in 1066. There is now some archaeological evidence that hospitals existed in England prior to the Normn conquest. Early hospital found in Winchester
  • Jan 1, 1191

    Importing drugs to hospitals

    Importing drugs to hospitals
    Drug trade was a good money making scheme during the middle ages as shown through customhouse records. Example of this was Port Acre (1191 - 1291) whic imported aloes, benzoin, camphor, nutmegs and opium.
  • Jan 1, 1470

    Taddeo Alderotti medical-case book

    Taddeo Alderotti medical-case book
    Taddeo Alderotti a Doctor in Italy, recorded the advice, based on experiential observations, in treating the Black Death that spread in 1348. A consilium was a doctor's written text in response to a particular case. Formula was :disease, patients age, sex, location, occupation and symptoms and the prescribed treatment. The Consilia of Gentile da Foligno (died 1348, most probably of the plague) were among the first medical texts to be printed call medical-case books.
  • Jan 1, 1510

    Leonardo Da Vinci

    Leonardo Da Vinci
    Leonardo drew many studies of the human skeletons, as well as muscles and sinews. He studied the mechanical functions of the skeleton and the muscular forces that are applied to it (science of biomechanics). He drew the heart and vascular system, the sex organs and other internal organs, being the first to draw a fetus in utero. He closely observed and recorded the effects of age and of human emotion on the physiology. He also drew those people with facial deformities and signs of illness.
  • Padua's anatomical theatre

    Padua's anatomical theatre
    Padua's famous anatomical theatre drew artists and scientists studying the human body during public dissections
  • Medical statistics

    Medical statistics
    Since the 16th century the parishes of London had compiled weekly Bills of Mortality, recording births and baptisms, and the age, sex, parish and apparent cause of death. Graunt studied these, and created statistical tables and drew deductions about demographics, epidemiology and social patterns. He was the first to recognize the importance of vital statistics and the need for reducing them to order, by mathematical calculations leading to conclusions about social and economic conditions.
  • First Blood Transfusion

    First Blood Transfusion
    In February 1665, Lower worked with Sir Edmund King, to transfuse sheep's blood into a man who was mentally ill. Lower was interested in advancing science but also believed the man could be helped, either by the infusion of fresh blood or by the removal of old blood. It was difficult to find people who would agree to be transfused, but a student, Arthur Coga, consented and the procedure was carried out by Lower and King before the Royal Society on November 23, 1667.
  • Richard Lower

    Richard Lower
    In the 1600's, it was thought that catarrh, an inflammation of the mucous membranes, might be caused by seepage of fluid from the brain to the nose. De Catarrhis, Lower's book, is of historical significance because it was the first attempt by an English physician to take a classical theory (that nasal secretions come from the brain) and to disprove it by scientific experiment.
  • Antony Van Leewenhoek

    Antony Van Leewenhoek
    Antony Van Leeuwenhoek's real contributions to microbiology came not just from his microscopes but,from his observations. He had drawings made of what he saw, and sent details to the Royal Society in London betwen 1673 until his death (age 90). He had no scientific training, but this was valuable as his descriptions were free of assumptions. For example, he observed "an unbelievably great company of living animalcules" in tooth plaque, without appreciating that these were bacteria.
  • James Jurin -mortaility statisitics

    James Jurin -mortaility statisitics
    James Jurin used an early statistical study to compare the risks of inoculation with those from contracting the disease naturally. He studied mortality statistics for London from 1709 -1723 and concluded that one fourteenth of the population had died from smallpox, up to 40 percent during epidemics. Jurin's analysis concluded that the probability of death from inoculation was roughly 1 in 50, while the probability of death from naturally contracted smallpox was 1 in 7 or 8.
  • James Lind and trial for scurvy

    James Lind and trial for scurvy
    James Lind a naval surgeon, conducted a clinical trial to assess therapies for scurvy.Sailors were put in pairs; all given identical diets, each pair received different supplements. Vinegar diluted sulfuric acid, cider, sea water, nutmeg, garlic, and horseradish mixed with two oranges and one lemon, daily.
  • Semmelweis tested his hypothesis about puerperal sepsis

    Semmelweis tested his hypothesis about puerperal sepsis
    Ignaz Semmelweis a Hungarian physician studied puerperal sepsis. His hypothesis was that infection was transported to uninfected patients by students. Medical students were asked to wash hands in chlorinated lime solution. Mortality rate dropped from 18.3% to 1.3% per year.
  • Statistics for cholera victims

    Statistics for cholera victims
    John Snow physician and Father of modern epidemiology for his work in tracing the source of cholera outbreak in Soho. Statistics illustrated the connection between water source and cholera cases.
  • Florence Nightingale

    Florence Nightingale
    In 1860 her work in 'Notes on Nursing' (1860), and was hugely influential for her concerns for sanitation, military health and hospital planning established practices. She compiled tables of statistics about how many people died, where and why during the Crimean war , to discover that in peacetime, soldiers in England died at twice the rate of civilians even though they were young and fit. The chart she showed the queeen (a coxcomb) helped reform the Military Health Service.
  • Pasteur discovered germs caused infections

    Pasteur discovered germs caused infections
    Louis Pasteur a French chemist and microbiologist discovered germ theory of infectious diseases. His research was based with wine growers to help with the fermentation process and develop a way to pasteurize and kill germs. Discovered staphylococci as cause of boils. Described Streptococcus pyogenes as cause of puerperal sepsis, and invented a vaccine for anthrax and rabies.
  • Frederick Henry Horatio Akbar Mahomed

    Frederick Henry Horatio Akbar Mahomed
    He was a pioneer of clinical medical research, he intiated the Collective Investigation Record (record of clinical, hereditary and anthropological features of disease) for the BMA. The organisation collected data from physicians practising outside the hopsital setting and was the beginning of modern colloborative clinical trials. He also was the first person in Britain to recognize that high blood pressure was a primary condition of kidney damage (and not the other way round).
  • Lister uses antiseptics to help sepsis

    Lister uses antiseptics to help sepsis
    Joseph Lister an English surgeon. His careful experiments with "carbolic acid" were the beginning of the end of post-operative sepsis. The carbolic sprays he advocated were initially messy and unpleasant.He would spray "carbolik acid" deterrent pungent antiseptic into the air in the operating room. The results are amazing, mortality decreased. Between the years 1861-1865, the average death rate in men 45%, while in 1869 before shrinking to 15% only.
  • Blinded, controlled randomised experiments

    Blinded, controlled randomised experiments
    Peirce was one of the founders of statistics. He formulated modern statistics in "Illustrations of the Logic of Science" (1877–8) and "A Theory of Probable Inference" (1883). With a repeated measures design, he introduced blinded, controlled randomized experiments in 1884 (Hacking 1990:205) (before Ronald A. Fisher). Peirce extended the work on outliers by Benjamin Peirce, his father. He introduced terms "confidence" and "likelihood" (before Jerzy Neyman and Fisher).
  • Pavlov's conditioning experiments

    Pavlov's conditioning experiments
    Pavlov showed the existence of the unconditioned response by presenting a dog with a bowl of food and the measuring its salivary secretions. However, when Pavlov discovered that any object or event which the dogs learnt to associate with food (such as the lab assistant) would trigger the same response. This must have been learned, because at one point the dogs did not do it. A change in behaviour of this type must be the result of learning.
  • Dr Albert Neisser infected patients intentionally

    Dr Albert Neisser infected patients intentionally
    The issue of informed consent had previously been controversial in German medicine in 1900, when Dr. Albert Neisser infected patients (mainly prostitutes) with syphilis without their consent. Despite Neisser's support from most of the academic community. Psychiatrist Albert Moll, was against Neisser. Neisser went on to be fined by the Royal Disciplinary Court, Moll developed "a legally based, positivistic contract theory of the patient-doctor relationship" that was not adopted into German Law.
  • Krasnogorski, Pavlov's associate

    Krasnogorski, Pavlov's associate
    Krasnogorski is responsible for the first definite application of the Pavlov method to normal children. Results from 1907 study of conditioned reflexes as developed in babies is detailsed. He went on to develop theories invloving six named conditioning reflexes.
  • Fisher and experimental design

    Fisher and experimental design
    Ronald Aylmer Fisher a mathematician showed randomization as an essential ingredient to the design and analysis of experiments, validating significance tests. His work on experimental design was first presented in his 1925 book aimed at agricultural research workers, One of its key features was the technique of random assignment of treatments or varieties to the field plots
  • Sollmann suggests using placebo control and blinded study

    Sollmann suggests using placebo control and blinded study
    Torald Sollmann suggests a placebo control and blinded observer as a solution to investigator bias.
  • Syphilis study at Tuskegee

    Syphilis study at Tuskegee
    In 1932, the U.S. Public Health Service began an investigation into Syphilis, in Tuskegee, in Alabama, Subjects were African-American descent. “ The Tuskegee Study of Untreated Syphilis in the Negro Male” (1932 – 1972) It involed 600 black men – 399 with syphilis, 201 who did not have the disease. Patients recruited without informed consent, they were not told they had syphilis, nor were they allow to recieve treatment, even after penicilin was the drug in 1947.The study lasted 40 years.
  • Sulfanilamide Tragedy

    Sulfanilamide Tragedy
    Sulfanilamide, used to treat streptococcal infections (tablet / powder form). Pharmaceutical company wanted to liquefy the drug to help market to children. In 1937, Harold Watkins, chief chemist for S.E. Massengill Co., discovered that he could use an inductrial chemical called Diethylene glycol (DEG) as a dissolving agent. He added raspberry flavouring and red colouring but DEG is a antifreeze, a deadly poison. They marketed 633 bottles but 100 patients died of kidney failure as a result.
  • Mustard gas, experiments

    Mustard gas, experiments
    Prisoners were deliberately exposed to mustard gas between September 1939 and April 1945 and other vesicants. These caused chemical burns and wounds were then treated to find out which was the most effective treatment.
  • Hill used randomisation in a trial

    Hill used randomisation in a trial
    Austin Bradford Hill was the first to design a clinical trial using randomisation in assigning study participants to the treatment groups. To test streptomycin and its therapeutic use against tuberculosis they used a control group. These participants would not receive the drug.
  • Sulfonamide experiments

    Sulfonamide experiments
    Experiments were conducted to investigate the effectiveness of sulfonamide. This is a antimicrobial agent. Wounds were inflicted on prisoners and infected with bacteria such as Streptococcus.Circulation of blood was stopped by tying off blood vessels with a tournaquet and wounds further infected with broken glass of wood shavings. Drugs were given such as sulfonamide to see if it was efective.
  • Mengele experimented on twins and gypsy's in Auschwitz

    Mengele experimented on twins and gypsy's in Auschwitz
    Josef Mengele was a doctor working in the concentration camps during World War II who conducted inhuman and unethical experiments to show similarities and differences between twins.
  • Entress, Vetter and Wirths carried out experiments at Auschwitz

    Entress, Vetter and Wirths carried out experiments at Auschwitz
    SS camp physicians Friedrich Entress, Helmuth Vetter, and Eduard Wirths carried out clinical trials of the tolerance and efficacy of new medications and drugs on prisoners. Those in particlar were prisoners suffering from contagious diseases, who had in many cases been deliberately infected.
  • Malaria experiments during Holocaust

    Malaria experiments  during Holocaust
    Malaria experiments were carried out between February 1942 - April 1945 on prisoners by injecting extracts of the mucous glands of females mosquitos. Prisoners (over a 1,000) were then treated with various drugs once they developed symptoms of the disease. Over half of the prisoners died as a result.
  • Freezing experiments conducted in Auschwitz

    Freezing experiments conducted in Auschwitz
    Freezing experiments withthe intent of discovering means to prevent hypothermia. Prisoners were forced to endure being in a tank of ice water for up to five hours. Or they were placed outside with temperatures as low as -6 C (21 F ) The experiments assessed also different methods of rewarming survivors.
  • Willowbrook Experiments

    Willowbrook Experiments
    From 1956 through 1971, residents at the Willowbrook State School for Children with Mental Disabilities were infected with live hepatitis in order to develop a vaccine. Parents gave permission for their children to participate in this study, often because it guaranteed acceptance into the overcrowded facility.
  • Thalidomide Tragedy

    Thalidomide Tragedy
    Thalidomide Disaster (1959-1960's) Developed by a German company Gruenenthal, Thalidomide was originally intended to help pregnant women rest, and help reduce morning sickness. Unfortunately, the drug caused birth defects when consumed during pregnancy. The most common and obvious was the shorted limbs known as phocomelia , meaning seal limbed. In this condition, the long bones of legs or arms are shortened or missing. The hands and feet also flipper like.12,000 children were affected.
  • Frances Oldham Kelsey

    Frances Oldham Kelsey
    United Staes were very lucky to have Frances Oldham Kelsey, as newly apponted member of the Food and Drug Aministration who refused to approve marketing of Thalidomide in the United States because of the lack of clinical data in safety reporting. She refused twice. This prevented thousands of birth defects in the United States.
  • Milgram's Shock Experiment

    Milgram's Shock Experiment
    Milgram (1963) was interested in researching how far people would go in obeying an instruction if it involved harming another person. Stanley Milgram was interested in how easily ordinary people could be influenced into committing atrocities for example, Germans in WWII.
  • Declaration of Helsinki

    Declaration of Helsinki
    The Declaration of Helsinki is a statement of ethical principles developed by the World Medical Association to: "provide guidance to physicians and other participants in medical research involving human subjects" (Para 1, Declaration of Helsinki). This includes research on people, identifiable human material or identifiable data. The Declaration was first adopted in 1964 and has since undergone several revisions (1975, 1983, 1989, 1996, 2000, and in 2008) .
  • Hofling Hospital Obedience Study

    Hofling Hospital Obedience Study
    In 1966, the psychiatrist Charles K. Hofling conducted a field experiment on obedience in the nurse-physician relationship. In the natural hospital setting, Nurses were ordered by unknown doctors to administer what could have been a dangerous dose of a (fictional) drug to their patients.This of course was against hospital procedure. Nurses were unaware they were involved in an experiement. Hofling found that 21 out of the 22 nurses would have given the patient an overdose of medicine.