Preclinical and Clinical Trial Requirements
All legal aspects surrounding preclinical and clinical trial requirements in Nigerian Pharma. Prepared in association with Olaniwun Ajayi LP, a leading law firm in Nigeria, this is an extract from The Pharma Legal Handbook: Nigeria, available to purchase here for USD 99.
1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?
Clinical trials are not required in all cases, clinical trials will be required to be conducted as a condition for marketing approval where there is a clear uncertainty of the efficacy of the test drug in the Nigerian population. It is considered unethical to continue to conduct clinical trials for a drug whose efficacy has been clearly established especially where there is no scientific reason to believe that available results cannot be generalised.
Thus, foreign drugs are subjected to clinical trials if the drugs do not have adequate and well documented use in black population or it has some race specific properties or its efficacy, safety and usefulness needs to be proven in the population.
Essentially, by the Food, Drugs And Related Products (Registration, Etc.) Act, a clinical trial is mandatory for the following:
- New or relatively new chemical entities or herbal formulations for which safety/efficacy profile has not been determined.
- Drugs for new indications.
- Drugs for new patient population group e.g. Age group and race.
- New combination drug products.
- New dosage schedule/regimen.
- New drug delivery system
- Academic clinical trials.
2. How are clinical trials funded?
Clinical trials are initiated and funded by sponsors who promote clinical study, testing or studying of a drug or medical device to ascertain its safety and effectiveness. The Good Clinical Practice Regulations 2009 defines a sponsor as “an individual, company, institution or organization which takes responsibility for the initiation, management and/or financing of a clinical trial” Clinical trials could be “industry sponsored” or “investigator initiated”.
In Nigeria, clinical trials are often funded by the sponsor pharmaceutical companies, academic medical centers, voluntary groups and international non-governmental agencies and other organizations whose main objective is to ensure that the clinical trials are successfully carried.
3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?
A key requirement of preclinical and clinical trial protocols is the presence of informed consent. Informed consent involves two essential components: a document and a process. The informed consent document gives a summary of the research project (including the study’s purpose, research procedures, potential benefits and risks, etc.) and explains the individual’s rights as a research participant. This document is part of an informed consent process, which consists of conversations between the research team and the participant, and may include other supporting material such as study brochures. The informed consent process provides research participants with ongoing explanations that will help them make informed decisions about whether to begin or continue participating in the research project.
Preclinical and clinical protocols like most clinical studies are based on a set of rules or directions. The protocol would often describe what types of people are eligible to participate in the study; the schedule of tests, procedures, medications and dosages and the length of the study.
There is no particular legislation which prescribes the contents of pre-clinical or preclinical protocols in Nigeria, however these protocols may contain the following basic and fundamental requirements:
- Background information
- Trial Summary
- Background to the Trial
- Aim, Hypothesis and Outcome of the Trial.
- Trial Design
- Eligibility Criteria for participants
- Informed Consent
- Safety considerations
- Study Overview
- Quality control and Assurance
- Ethical considerations
- Sponsor (funding)
- Insurance and Indemnity
- Financial Support
Two regulatory authorities are responsible for the grant of approval of the protocols: the National Agency for Food and Drug Administration and Control (NAFDAC) and the National Health Research Ethics Committee (NHREC) (acting through Independent Ethics Committees (IEC)). Initial approval of the protocols are done by the Independent Ethics Committees (IEC) accredited by the National Health Research Ethics Committee (NHREC) which body gives ethical opinion on study protocols to NAFDAC depending on the number of trial sites involved.
Ethical clearance is granted by the IEC on the protocol, the initial approval or opinion on the protocols is granted by NHREC and the final approval is granted by the National Agency for Food and Drug Administration and Control (NAFDAC) in terms of the Food, Drugs And Related Products (Registration, Etc.) Act.
In order to reduce processing timeline for Clinical Trial applications, the study protocol can be submitted simultaneously to NAFDAC and the Ethics Committee.
4. What are the requirements for consent by participants in clinical trials?
In Nigeria, this is unarguably essential in the ethical conduct of research in general and clinical trials in particular. The Good Clinical Practice Regulations defines informed consent as the “Decision, which must be written, dated and signed, to take part in a clinical trial, taken freely after being duly informed of its nature, significance, implications and risks and appropriately documented, by any person capable of giving consent or, where the person is not capable of giving consent, by his or her legal representative; if the person concerned is unable to write, oral consent in the presence of at least one witness may be given in exceptional cases”.
Potential subjects should thus be informed of the objectives and methods of the study, the drug product and treatment regimen, the available alternative treatments, potential risks and benefits, and of possible complications and discomforts, which may arise from participation in the study.
Based on information received and understood, the potential subject freely gives consent to participate in a study, this is known as informed consent. This consent should not be obtained through inducement or coercion and the subject should be aware that he/she may withdraw from the study at any time, and this will not affect his/her future medical care in any way; thus consent can only be sought under circumstances that provide the prospective participant or the representative sufficient opportunity to consider whether or not to participate and the circumstances shall minimize the possibility of coercion or undue influence.
The NHREC has made recommendations on the contents of the informed content document and process. The informed consent document should contain the following aspects:
- Title of the research
- Name(s) and affiliation(s) of researcher(s) of applicant(s)
- Sponsor(s) of research
- Purpose(s) of research
- Procedure of the research, what shall be required of each participant and approximate total number of participants that would be involved in the research.
- Expected duration of research and of participant(s)’ involvement.
- Costs to the participants, if any, of joining the research
- Alternatives to participation
- Incentive (inducement) to participants
- Consequences of participants’ decision to withdraw from research and procedure for orderly termination of participation.
- Modality of providing treatments and action(s) to be taken in case of injury or adverse event(s).
- What happens to research participants and communities when the research is over?
- Statement about sharing of benefits among researchers and whether this includes or exclude research participants.
- Any apparent or potential conflict of interest.
- Detailed contact information including contact address, telephone, fax, e-mail and any other contact information of researcher(s), institutional HREC and head of the institution.
All consent process must be documented and in circumstances where participants are unable to provide signed consent, other alternatives such as thumb printing and witnessed audio recording may be carried out.
Where the investigator fails to obtain informed consent of participants, this may raise grievous ethical questions which may lead to actions against the investigator. The Pfizer Trovan 1996 case gives credence to this.
5. May participants in clinical trials be compensated?
Indeed. while there are no specific provisions regarding the manner, amount and method of compensation, most studies offer monetary compensations to participants for the time they spent participating in a trial, this amount is given to cover expenses for transportation, meals, and possibly, for lost work time; payment may however not be substantial enough to constitute inducement to participate for monetary gain.
Aside from the above and as a way of alternative compensation, sponsors, researchers and investigators may make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This is often crucial in novel breakthrough drugs for life threatening or terminal conditions especially as participants are usually concerned about the affordability or availability of the drug after the successful trial. Also, patients who have been recruited as participants in a drug trial may also be allowed access to ancillary care for health conditions that though are unrelated to the trial but might have been discovered during the course of the trial.
It is necessary that the investigator ensure that all relevant information regarding compensations, payments or reimbursements are contained in the protocol.
6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?
The starting point of explaining this under the Nigerian pharma-legal sphere would be noting the provisions of the Good Clinical Practice Regulations on this subject which provides that “no informed consent, whether oral or written, may include any exculpatory language through which the participant or the representative is made to waive or appear to waive any of the participant’s legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability of negligence”
Participants are protected first by being told honestly and without bias, what the known and potential risks are for participating in the trial. This information is to be presented to participants in the language they understand and are to form part of the informed consent document.
The Regulations also makes it mandatory for provisions regarding insurance and indemnity to cover the liability of the investigator and sponsor which may arise in relation to the clinical trial. Thus, in a typical clinical trial, insurance is provided to cover participants in case of any trial related injury that may be sustained by any participant. This way, participants of various clinical trials are protected by virtue of the insurance and or indemnity provisions contained in the Clinical protocol. It is worthy of note that where such provisions are not contained in the trial protocol, the Committee or NAFDAC might not grant final approval to such protocol and therefore the trial might not proceed.