Steps in Conducting a Research Study
Research must be conducted systematically and this involves various standards, regulations and legislations that must be followed. The responsible conduct of research will ensure a research site’s success.
Research Site Selection and Approvals
The sponsoring company will identify qualified sites and investigators for their research trial. In doing so they consider the following elements: location of the site, team members, qualifications, site history, past clinical trial experience, site specialty, and patient population.
Once your site has been selected, your clinic needs to receive approval from several regulatory authorities and have preparations in place prior to asking subjects to participate in a trial. In Alberta, your must seek approval from your local Research Ethics Board (REB) in order to ensure the various study documents (including the study protocol) meets the highest ethical standards. If you are conducting research at the University of Alberta, or the University of Calgary you must obtain ethics approval from the University’s ethics board. If you are conducting research in the community not associated with a university you must obtain ethics approval through the Health Research Ethics Board of Alberta (HREBA).
More about Alberta Ethics
An ethics board is an independent board that contain members from medical, scientific and non-scientific backgrounds. They are responsible for reviewing all protocol specific paperwork and items involved in obtaining informed consent in order to approve and complete ongoing review of research trials. They will consider scientific and ethical aspects of these trials. Research sites are also required to report adverse events deemed serious, safety reporting provided by sponsors, protocol deviations impacting patient safety and annual study reports to their ethics board.
In Alberta, the ethics board is the Health Research Ethics Board of Alberta (HREBA) and it houses three separate committees:
- HREBA – Clinical Trials Committee (CTC) that reviews research proposals conducted by physicians in Alberta.
- HREBA – Community Health Committee (CHC) that reviews community health research in both urban and rural areas across Alberta.
- HREBA – Cancer Committee (CC) that reviews all new and ongoing research proposals conducted in the therapeutic area of cancer.
As of February 25, 2014 all new protocols are submitted to HREBA by an online system called IRISS for local submission of research proposals for approvals. Please visit their website for more information and regulations.
Subject Recruitment
Subjects are selected based on specific criteria that must be met and are outlined in the research protocol supplied by the sponsor. Subject recruitment may include your current patient chart reviews based on study criteria, radio and newspaper ads, flyers, articles in local newsletters, public service announcements, and in clinic brochures. You may consult other clinics, organizations, or healthcare professionals to refer subjects to your study. Individuals interested in participating in the clinical trial must meet certain requirements (eligibility criteria) and must be willing to sign an informed consent.
Obtaining Informed Consent and Screening for Eligibility
Informed consent is the process of giving a potential participant all of the key facts about a study so they can decide if they would like to be involved. Informed consent would include information about how the study would be conducted, including methods and procedures, as well as the potential risks and benefits, of participating in the study. Consent must be given freely and with out undue influence.
Once the subject signs informed consent, they must go through a screening process that ensures they meet the criteria that the sponsor requires for the study. This is necessary prior to a potential subject becoming actively involved in a research study. The study staff will conduct several tests and procedures to ensure suitability and safety of participation.
Randomization
If participants meet the eligibility criteria and provide informed consent they will be enrolled in the clinical trial and then randomized to either the treatment or control group. Randomization is done to improve the strength of the results of a clinical research trial by preventing bias and by testing the true efficacy of the study treatment by comparing it to a control group.
There are many ways randomization of study subjects is done. Commonly it can be quite simple and the chance of being placed in a particular treatment group is determined by chance, equivalent to rolling a dice or flipping a coin. Having a control group increases the strength of the study results. This group is not exposed to the study drug and often receives a placebo.
Use of Placebo
A placebo is an inactive substance; it has no medication (drug) in it. It looks the same as the real medication. A placebo is used in order to “blind” the study so neither the participant nor the study doctor will know whether they are on the active drug. This is done so that the participant and the study doctor will not be influenced by expectations of the effects of the drug.
Follow-up Phase
For the duration of the clinical trial the participant will remain in contact with the research team either by telephone or through clinic visits, based on the study visit schedule. No changes to treatment administration will take place in this phase unless indicated study protocol or by standard practice.
Withdrawal of Consent
It is important to remember that patient participation in any study is entirely voluntary. As such, patients are free to withdraw from the study at any time with out providing a reason for withdrawal. Withdrawal of consent indicates that the subject would like to withdraw participation in any and all research related activities from this point forward.
Discontinuation of Treatment
In some cases the subject will be taken off the study treatment but will continue with study visits and procedures as planned for continued safety evaluation.
End of Study and Analysis of Results
Study subjects complete the study and are taken off any treatment or intervention that they were randomized to. The outcomes of the study will be compiled and analyzed by the sponsor and research team. A description of the study will be published to www.clinicaltrials.gov as required by national law. The results found from the study can help to create treatments and fuel future research.
Monitoring and Auditing for Quality Assurance
Monitoring and auditing occur throughout the trial for quality assurance purposes. Clinical research auditing and monitoring serve two different functions. Monitoring ensures that the research trial is compliant to the most up-to-date research protocol, established Standard Operating Procedures (SOPs), Good Clinical Practice (GCP) and other applicable regulations. It is commonly conducted by an appointed representative from the research sponsor and occurs on a regular basis as the study progresses. Results are shared with the study site on a regular basis along with suggested corrective actions. Auditing follows the same process and is very systematic, however it is an independent organization that examines the conduct of the study e.g. Health Canada. If the site is found have deficiencies in its audit, the site can be issued a warning or more severely, be shut down and exempt from conducting further research trials. Monitoring and auditing are in place to ensure the research study is being conducted according to the research protocol, follows ethical responsibilities, and meets the requirements of conducting a well run research study according to regulations in place.