Dr. Anthony Leachon
Drug trials offer a chance to participate in the development of potentially effective therapies. Whether or not to participate in this is a complex decision. To be a Principal Investigator in a drug trial requires a substantial commitment of both time and effort. So it is a most important to know the responsibilities and the appropriate regulatory requirements when performing drug trials. The scientific, practical and financial implications should be weighed. Nevertheless, there are usually clear rewards in doing clinical trials.
The Principal Investigator
The Principal Investigator (PI) is usually an academic clinician working at a reputable institution and an expert in the particular field of clinical medicine of interest. The PI must be appropriately educated, trained and experienced in conducting drug trials. He or she must have adequate time, access to patients, clinical, technical and other capabilities, space and other facilities. As the PI is almost always a busy person, there needs to be some incentive for him to allocate previous time to perform a study. Investigators have different reasons for participating in a drug trial: for the pure science of study, for clinical merit of the study, potentially useful data for future publication or for financial gain. Depending on the type of study, pharmaceutical companies may require a PI to sign an investigator’s agreement that states that trial data belong to the company or impose some restriction on the publication of data.
The PI should have support from a team of doctors, nurses and other research personnel. The PI responsibilities can be delegated to a sub-Investigator (SI), who may regularly make important trial-related decisions. An SI needs to be closely supervised, suitably educated and qualified and be familiar with Good Clinical Practice (GCP). But the ultimate clinical responsibility still rests with the PI who will be medico-legally responsible for all breaches in patient confidentiality and any incidents of medical negligence, etc.
Responsibilities of a Principal Investigator:
Based on GCP, the Investigator:
• Must be qualified by education, training and experience to assume responsibility for the proper conduct of the trial.
• Should be thoroughly familiar with the appropriate use of investigational drug in the current Investigator’s brochure or in the product information.
• Should be aware of, and should comply with GCP, and applicable regulatory requirements
• Should permit monitoring and auditing by the sponsor, and inspection by the appropriate regulatory authorities.
• Should maintain a list of appropriately qualified persons to whom the investigator has delegated significant trial-
• Should have adequate resources such as required subject population, sufficient time, and adequate staff and facilities.
• Should be responsible for the medical care of subject trials.
• Should have primary responsibility in communication with the Institutional Review Board/Independent Ethics Committee which includes obtaining written and dated approval/favorable opinion, providing all documents subject to review, submitting progress report and study termination or final study report.
• Should conduct the drug trial according to protocol and should not deviate from it.
• Should be responsible in obtaining informed consent from trial subjects.
• Should ensure accuracy, completeness, legibility, and timeliness of data reported.
• Should be report all adverse events and do so promptly if serious.
Standards in Conducting Drug Trials
There are certain standards and rules and regulations being followed in conducting drug trials. As discussed earlier, one of the responsibilities of a principal investigator is to be aware and comply with GCP and appropriate regulatory requirements.
Good Clinical Practice (GCP)
GCP is an international, ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve participation of human subjects.
The Do’s in drug trials based on GCP are the following:
• The rights, safety and well being of trial subjects should be protected
• Conduct of drug trials should be consistent with the principles that have their origin in the Declaration of Helsinki
• And, that the clinical trial data should be credible
In many countries, implementation of GCP in all phases of drug trials is a legal requirement. Although not yet implemented in the Philippines, most pharmaceutical companies adhere to GCP in the conduct of their trials.
In addition to the do’s mentioned above, clinical research personnel and investigators should have a good and thorough understanding of the principles of GCP, and fully appreciates the interpretation and practical application of these guidelines and regulations.
Bureau of Food and Drug (BFAD)
A.O. No. 22-A S. 1982 is about the research policies and guidelines by the Department of Health (DOH). This mentioned that while collaborative research endeavors are being encouraged and supported by the DOH, safeguards in the conduct of these research activities to ensure the safety and welfare of human subjects and the pubic are also imposed. So DO NOT do any research until l such approval is obtained.
A. Registration of New Drug
• Based on BFAD Operation Manual on Drug Evaluation and Control (1992), one of the requirements of BFAD for registration of new drug is data from drug trials. These data are the basis in designing the most appropriate treatment of future patients with a given medical condition.
B. Monitored Release Prior to Approval of General Use
Investigational New Drug (IND), New Drug (ND) and Newly Introduced Drug (NID) will be required to complete pharmacological studies and pass through a 3-year monitored release before becoming eligible for application and approval for general use. They are referred to as Post Marketing Surveillance (PMS) studies.
The model protocol for monitored release would include an uncontrolled clinical study reporting the therapeutic effects and adverse reaction for 1000 patients per year or 3000 patients over 3 years, provided however that if the drug product is for a very limited therapeutic indication the 1000/year patient requirement will be waived and only 10% of the total patients given the drug will be required to be monitored and reported to BFAD by the pharmaceutical company.
Pharmaceutical Healthcare Association of the Philippines (PHAP)
The Pharmaceutical and Healthcare Association of the Philippines (PHAP) is a business association representing the providers of most of the country's medicines. Members include the country's leading research-based companies of pharmaceuticals and medical services.
PHAP has given their share of voice by providing additional guidelines in the conduct of PMS studies to pharmaceutical companies who are PHAP members. These guidelines set the objectives pharmaceutical companies must DO:
• To protect the true scientific purpose of PMS studies
• To distinguish between true PMS and marketing-inspired activities being passed on as PMS
• To rationalize current practices as to patient recruitment and remuneration.
This guidelines clearly state that remuneration or compensation of physicians enrolled must be provided within a reasonable amount. Pharmaceutical companies should not do things that will induce doctors to prescribe a particular drug. So pharmaceutical companies should only conduct PMS to monitor efficacy and possible adverse drug reactions and not to influence prescription habits of physicians.
Making a Decision
Reviewing an offer to participate in a drug trial is an Investigator’s option. In order to make an informed decision, the following questions regarding participation should be asked:
- What question does the trial address?
- Is the study likely to achieve its objectives?
- What population of patients will the trial enroll?
- What impact will the trial have on patients?
- What are the benefit and risks on my patients?
- How will the data be collected and recorded?
- What staff will be required to perform the trial?
- What will the cost be?
- Is the payment schedule optimal?
The goal of drug trials is to determine if a treatment both works and safe. Awareness and adherence to the standards of Good Clinical Practice, the local regulatory requirements of the Bureau of Food and Drug and the ethical guidelines set by PHAP is a must for everybody who will participate in such endeavor. One has to recognize the importance of doing drug trials since this will definitely provide access to new research treatment that will be of benefit for mankind.
Department of Health, Administrative Order No. 22-A S. 1982