Clinical trials are research studies on human subjects that are designed to answer specific questions about an intervention (novel vaccines, new medication, new treatments, functional foods, dietary supplements, devices or new ways of using known interventions), with the objective of generating safety and efficacy data.
Clinical trials are designed to answer the following questions; does the intervention work, is it an improvement, or at least is it as good as currently proven options, and finally is it safe. Clinical trials are conducted in a highly regulated manner to ensure the protection of participants. They are conducted only after satisfactory information has been submitted and approved by the relevant health authority and ethics committee in the country where approval of the trial is sought.
Clinical Trials are led by specialists in a particular field referred to as Investigators. The type and the phase of the trial will be determined by how far through the pre-specified stages of development the process is. Depending on product type and development stage, investigators initially enroll volunteers and/or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. As positive safety and efficacy data are gathered, the number of patients typically increases. Clinical trials can vary in size, and can involve a single research entity in one country or multiple entities in multiple countries.
The primary purpose of trials is to develop newer medicines that are either more effective, safer or have a better compliance so as to improve the standard of care.
The endpoint of a trial is to generate data to ensure registration of new medications by the leading health authorities of the world so that other patients can have access to new treatments not in a trial setting. Some trials are designed to prove efficacy in a new indication for a drug that is already registered.
Clinical trials are run by sponsors, sponsors may be academic institutions, pharmaceutical companies etc. The sponsor has a hypothesis that they are seeking to prove by conducting a clinical trial. The sponsor designs a protocol, which documents how the trial will be conducted. Sponsors select Investigators to conduct clinical trials on their behalf. These Investigators are qualified by experience and education to do so. The sponsor will ensure financial support as well as the commitment to provide the investigational agents. Clinical trials are extremely expensive and large amount of funding is required to provide for expensive laboratory tests, patient follow-up as well as support the investigators.
The conduct of clinical trials is governed by national guidelines that are based on the ICH (International Conference Harmonisation) that governs amongst other elements GCP (good clinical practice).
The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is unique in bringing together the regulatory authorities and pharmaceutical industry of Europe, Japan and the US to discuss scientific and technical aspects of drug registration. Since its inception in 1990, ICH has gradually evolved, to respond to the increasingly global face of drug development, so that the benefits of international harmonisation for better global health can be realised worldwide. ICH’s mission is to achieve greater harmonisation to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner.
The ICH topics are divided into four categories:
1. Quality Guidelines
2. Safety Guidelines
3. Efficacy Guidelines
4. Multidisciplinary Guidelines
GCP –Good Clinical Practice
GCP enforces guidelines on the ethical aspects of the conduct of a trial. Standards are set in terms of comprehensive documentation of the protocol, record keeping, training, and facilities including computers. Quality assurance and inspections ensure that these standards are achieved. GCP aims to ensure that the studies are scientifically authentic and that the clinical properties of the investigational product are properly documented. GCP guidelines are used in clinical trials throughout the globe with the main aim of protecting and preserving human rights. GCP provides investigators and their study teams with the tools to protect human subjects and collect quality data. In South Africa we have localised GCP guidelines which are used together with the International guidelines called SAGCP.
Patients need to present to a Physician who is acting as an Investigator for a particular trial or they need to be referred to the site by a referring physician who is aware of the trial. Patients may also respond to an advertisement that has been approved by an ethics committee. Once patients have reached a clinical trial site they need to sign an informed consent document that will allow them to be screened for trial entry. Patients need to meet what are known as “inclusion and “exclusion” criteria. On that basis the investigator can assure the regulatory authority that a specific intervention has been tried in a specific group of patients.
A person who meets the inclusion/ exclusion criteria, is fully informed of the risks/ benefits as per the Informed consent process, and who stands to access treatment for an unmet medical need should consider a clinical trial.
Clinical trials are conducted at clinical trial sites that have undergone a rigorous selection and qualification process and may also be conducted at private practices or at public hospitals.
1. Trials can be classified as to whether they are interventional or non- interventional i.e. registries
2. Trials may be classified on the Phase of the research – I, II, III, IV
3. Trials may be retrospective or prospective
4. Trials may be randomised
5. Trials may be placebo-controlled.
There is a triple check of suitability of sites.
1. The sponsor, in addition the commitment of the investigator who will secure the rights of the patient
2. The regulatory Authority in South Africa this is known as the MCC –Medicines Control Council
3. The Institutional Ethics Committee that is specifically constituted as per GCP requirements.
Anyone considering a clinical trial should also know that there are benefits and risks associated with participating.
• Patients have limited access to treatment options
• The patient’s disease constitutes an unmet medical need
• The patient wants to contribute to medical science
Safety/ Toxicity issues associated with the investigational compound, which have not yet emerged.
Clinical trials and breast cancer
Metastatic Breast cancer is an unmet medical need. New treatment options are needed for patients in this setting so as to prolong life without compromising quality of life. Trials are also being designed to look at treatment in the neo-adjuvant setting for breast cancer i.e. treatment before surgery to look at the role of this therapy in terms of impacting long-term outcome.
Advise when considering getting into clinical trials
• Trust your Investigator
• Read the informed consent document
• Discuss the risks and benefits of being on the trial as compared to not enrolling on the trial.
Remember that once you give consent you remain free to stop participation at any time point without providing a reason.
There is a website www.clinicaltrials.gov where people can search by disease, country, molecules etc.
There is also a South African website available that lists all clinical Trials approved by the MCC (Medicines Control Council) for South Africa www.sanctr.gov.za
Written by Michelle Blou (Medical Director Oncology of Novartis SA)