GCP Lesson
Good Clinical Practice
Responsibility of the Medical Research Team to follow GCP Guidelines and Regulations

• Protecting Research Subject Volunteer Rights and Safety in the Clinical Trial
• Ensuring Accurate and Reliable Data Collected that is Easily Verifiable

What is GCP?

1. A set of international standards ensuring the rights, safety, and well being of trial subjects are protected.
2. A process which ensures data resulting from the trail is complete, accurate and unbiased.

History of Pharmaceutical Medicine

1. In 1906 the Pure Food and Drug Act was passed, partly due to Dr. Wiley's Poison Squad experiments. It forbade interstate and foreign commerce of adulterated and misbranded food and drugs. There were no safety or efficacy requirements. In 1902 Dr. Wiley started research with human volunteers to determine the effects of food preservatives on digestion and health. Overnight the press made the "Poison Squad" a national sensation. This law required new drugs be tested for safety before marketing, the results of which would be submitted to the FDA in an NDA or New Drug Application. The law also required that drugs met standards of strength and purity and had adequate labeling for safe use.
2. The Elixir Sulfanilamide tragedy in 1937 prompted Congress to pass the Food, Drug, and Cosmetic Act in 1938, which required pre-market review of safety in a New Drug Application (NDA) and specified labeling requirements. It also began marking study drugs with the phrase, “for investigational use.” It also gave the FDA the authority to inspect sponsor drug manufacturing plants and gave them more enforcement power. The requirement of proving effectiveness was still missing.
3. In 1948 the Nuremberg Code was written, the first formal statement on medical ethics. Nuremberg Code: In 1948, the Nuremberg Code laid down 10 standards for physicians to conform to when carrying out experiments on human participants. The Nuremberg Code was the result of judgment by an American military war crimes tribunal conducting proceedings against 23 Nazi physicians and administrators for their willing participation in war crimes and crimes against humanity. The doctors had conducted medical experiments on concentration camp prisoners who died or were permanently affected as a result. The Nuremberg Code was developed in response to the judicial condemnation of the acts of Nazi physicians, and did not specifically address human subject research in the context of the patient-physician relationship. Briefly the 10 standards of the Nuremberg Code are as follows:
1. Volunteers freely consent to participate
2. Researchers fully inform volunteers concerning the study
3. Risks associated with the study are reduced where possible
4. Researchers are responsible for protecting participants against remote harms
5. Participants can withdraw from the study at any time
6. Qualified researchers conduct the study
7. Cessation of the study if adverse effects emerge
8. Society should benefit from study findings
9. Research on humans, should be based on previous animal or other previous work
10. A research study should never begin if there is a reason to believe that death or injury may result.
4. The thalidomide tragedy of the 1950s led to the 1962 Kefauver-Harris Amendments, which required proof that drugs are both safe and effective before marketing them and provided the basis for the current IND (Investigational New Drug application). A drug tragedy in Europe, the births of thousands of deformed infants whose mothers had taken the new sedative thalidomide, focused public attention on pending U.S. legislation to further strengthen the Federal Food, Drug, and Cosmetic Act. The Drug Amendments of 1962 passed unanimously by the Congress, tightened control over prescription drugs, new drugs, and investigational drugs. It required sponsors to send pre-clinical data to the FDA prior to beginning phase 1 study. It required obtaining Informed Consent prior to placing a person in a trial. It also required sponsors to report all findings to the FDA. It was recognized that no drug is truly safe unless it is also effective, and effectiveness was required to be established prior to marketing — a milestone advance in medical history. Drug firms were required to send adverse reaction reports to FDA and drug advertising in medical journals was required to provide complete information to the doctor — the risks as well as the benefits. In the years since 1962 literally thousands of prescription drug items have been taken off the U.S. market because they lacked evidence of safety and/or effectiveness, or they have had their labeling changed to reflect the known medical facts.
5. In 1964 the Declaration of Helsinki was written. It specifies ethical principles for medical research involving human subjects. It was adopted in Finland by the 18th World Medical Assembly. It is frequently amended and is considered the definitive document on how to properly conduct ethical medical research.
6. From 1932-1972 the Tuskegee Syphilis Study looked at the effects of untreated syphilis; this led to the National Research Act and the Belmont Report which led to the FDA proposing regulations on the Obligations of Sponsors and Clinical Investigators. The IRB (Institutional Review Board) was set up to oversee medical research involving human subjects to ensure validity and patient protection.
7. In 1979 the Belmont Report was published, which established three basic ethical principles for the treatment of human subjects in research: respect for persons, beneficence, and justice.
8. In 1983 the Orphan Drug Act was passed, which gave incentives to sponsors to develop drugs that would otherwise not be profitable to develop because of their small patient population.
9. In 1984 the Waxman-Hatch Act was passed, which enabled the manufacturers of generic drugs to submit an abbreviated new drug application (ANDA) to market their generic drugs.
10. The 1987 IND Rewrite Regulations made final new procedures in 21 CFR Part 312 for FDA review of investigational new drug applications and for monitoring the progress of investigational drug use.
11. In 1988 Expedited Drug Development, also known as Subpart E, allowed a compressed approval schedule for sponsors of drugs for serious and life-threatening illness for which no alternative exists.
12. In 1996 the ICH (International Conference on Harmonization) was formed in Brussels. This is a consolidated document setting out a tripartite standard for the conduct of clinical trials.
13. In 1992 PDUFA allowed FDA to collect fees from companies for the review of certain applications, including product and site fees; this resulted in significant improvement in review times.
14. The 1993 Accelerated Approval Procedures allowed accelerated approval procedures for new drugs and biologics that have been studied to treat serious or life-threatening illnesses.
15. In 1997 FDAMA extended PDUFA, reduced review times, enabled fast track products, increased patient access to experimental drugs, and gave pediatric exclusivity to eligible manufacturers.
16. In 2001 the EU Directive on the Conduct of Clinical Trials in the European Union was introduced. This directive added further guidance and direction on aspects of running a clinical trial, in particular with reference to gaining approvals to run trials via country competent authorities and the role of ethics committees. The directive was converted into each countries law from May 2004.

Sincerely:

Joseph Saponaro, MD, DABIM, FACP, CPI, CCI, CCTI, CCRC, CCRP
Board Certified Internist, JPMC
Principal Investigator, DSI
Diplomat American Board of Internal Medicine
Fellow American College of Physicians
Certified Physician Investigator by the AAPP
Certified Clinical Investigator by the DIA
Certified Clinical Trial Investigator by the ACRP
Certified Clinical Research Coordinator by the ACRP
Certified Clinical Research Professional by SoCRA
Member: The American College of Preventive Medicine
Founder, CertifiedResearchers.com