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On Conducting Clinical Trials
May 10, 2006
I experimented with guinea pigs in college but dealing with human subjects is a different story. You have to strictly follow certain guidelines. One doctor once applied for a clinical research job. He was not considered because he did not have the experience. Indeed, pharmaceutical companies consider clinical trials a serious matter. We have heard of drugs being pulled out of the market because of side effects. I am writing this article for those interested to go into the clinical research field, a career option one can pursue because there are opportunities both locally and abroad. I will be talking about what it takes to be in this field and how to go about conducting clinical trials.
There are guidelines which have been established for clinical research involving human subjects. The Guideline for Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. The World Medical Association has also developed the Declaration of Helsinki as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects. “It is the duty of the physician to promote and safeguard the health of the people. The physician’s knowledge and conscience are dedicated to the fulfillment of this duty.” The Declaration of Geneva binds the physician with the words, “The health of my patient will be my first consideration,” and the International Code of Medical Ethics declares that, “A physician shall act only in the patient’s interest when providing medical care which may have the effect of weakening the physical and mental condition of the patient.”
Clinical trials are conducted as required by the Bureau of Food and Drug or BFAD (Food and Drug Administration or FDA in the U.S.) for the approval of an Investigational New Drug (IND). Drug development involves several phases. It starts with a preclinical testing which deals with laboratory and animal studies. INA Research Philippines, based in Laguna, conducts preclinical testing using cynomolgus monkeys, which are indigenous in the country. Phases I, II and III involve clinical trials. Pharmaceutical companies either would conduct the trials themselves or would hire a Contract Research Organization or CRO like Quintiles or Gleneagles to do the job. Phase I uses healthy volunteers to determine the toxicity (safety and dosage) of a drug. In studies on anticancer drugs, phase I is not performed anymore. It would be unethical to do so. Phases II and III deal with patient volunteers (those with the disease) and are done to determine the efficacy (effectiveness) of the drug. Although in literature, phase II usually involves 100-300 subjects and phase III involves 1000-3000, the number of subjects would really depend on the prevalence of the disease as based on statistics. It would be the job of the statistician to determine the sample size.
A phase IV or post-marketing surveillance (PMS) is performed to monitor the adverse events to the drug. Adverse event is any untoward medical occurrence or experience in a subject which occurs following the administration of the trial drug. This would include any unfavorable sign or symptom or an abnormal laboratory finding. An adverse event is considered serious if it results in death, a life threatening event, or hospitalization. A Serious Adverse Event (SAE) is reported within 24 hours of the initial observation of the event.
Before a clinical trial can be conducted, it should be approved by BFAD and the Ethics Committee (EC) of the hospital or institution where the study will be done. The ethics committee is known as Research Implementation and Development Office – Ethics Review Board (RIDO-ERB) at UP-PGH and as Tropical Disease Foundation – Institutional Review Board (TDF-IRB) at Makati Medical Center. During my recent visit to the WVSU College of Medicine, I was informed by the dean that they have an ethics committee approved by the Board of Regents of the university. The WVSU Medical Center is very willing to participate in multi-center clinical trials.
There are usually three documents that are submitted to BFAD and the ethics committee for review and approval. First is the clinical research protocol, which contains the study rationale, objectives, design and methodology, inclusion criteria, exclusion criteria, and analyses. Second is the Case Report Form (CRF) where the patient data like demographics, drug dosage, laboratory results, concomitant medications, and adverse events are recorded. And third is the Informed Consent Form (ICF), which the patient signs if he/she agrees to participate in the study.
Physicians play an important role in conducting clinical trials. Consultants (specialists in the field of study) act as investigators. They convince patients to participate in the study and they document all significant findings in the CRF. Usually, a senior consultant would serve as Principal Investigator (PI), a junior consultant as co-investigator, and fellows/residents as sub-investigators.
If you are not a consultant or a fellow/resident in training, you may still be part of the clinical research team as a Clinical Research Associate (CRA). Recently, I have heard of the term Doctor-CRA, which is in demand nowadays.
My first job was as a contractual CRA for a pharmaceutical company. I was referred by a medical representative. The district manager called me for an interview at Sarabia Manor Hotel and Convention Center in Iloilo City. The study drug will be used for the treatment of type II diabetes mellitus. So, I had to discuss with the interviewer the four classes of oral hypoglycemic agents which are sulfonlylureas (glipizide and gliclazide), biguanides (metformin), alpha glucosidase inhibitors (acarbose), and thiazolidinediones or insulin sensitizers to which the study drug belonged. The next day, I was given a round-trip plane ticket to Manila with free hotel accommodation for training. And for the next six months, I traveled from Iloilo to Antique to Capiz and to Aklan (including Boracay) conducting the trials.
Two years after my first experience with clinical research, I found this ad in the newspaper:
CLINICAL RESEARCH ASSOCIATE
- Bachelor’s degree in Medical Science
- At least 2 years experience in Clinical Research
- Experience in conducting all areas of the clinical monitoring process in accordance with GCP and company SOP
- Knowledge in GCP and has implemented GCP trials
- Able to facilitate effective communication between the investigative site and the company through written, oral, and/or electronic process
- Results-oriented, bright, dynamic, resourceful and aggressive with above average influencing skills
- Computer literate with effective interpersonal and communication skills
I took my chances and applied for the job. However, it was difficult persuading the clinical research consultant because I did not have enough experience. He told me to be honest on what I do not know about clinical research because he will be willing to train me. For the next two years, I had the opportunity to work as part of the clinical research team. I was like in a residency training program because the consultant got me involved in the management of the study patients. I even had to make orders in the chart in his behalf. At the same time, I was learning several aspects of clinical research like documentation and reporting, budgeting and project management. Just recently, our clinical research consultant was appointed as director of one of the government hospitals in Manila. He wanted me to work for him as executive assistant, which is another great opportunity to learn. But before I shift to hospital administration, the skill I will be developing on that job, I plan to maximize first my experience in clinical research. After all, clinical research is not just a job, it is a career.
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Views expressed on this column and any other by-lined articles on this site are the authors' own and do not necessarily reflect the views of the organization or its members.
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