Proper strategic planning is a critical component to any study. Start with the end in mind:
- What is the purpose of the study?
- What claims and/or registrations do you intend to support?
- What piece of scientific knowledge do you intend to uncover?
- What questions need to be answered?
Once you have gained an understanding to these questions, you can begin the process of designing a study appropriate to the investigation of these questions.
Initial strategic planning and needs assessment will take several hours of conference calls and meetings to determine the needs of the study. Best Practice involves a standard set of questions, including information regarding the study product mechanism of action, dosage, and usual treatment cycle. Questions regarding marketing intent, study population (based on whom you intend to market the product to), outcomes, and endpoint selection are asked as well.
All prior data (including traditional use, preclinical, and animal data) on the study product must be reviewed. If there is only limited prior data on the actual study product, a full literature review on the therapeutic area and competitive products may be required. There are more than 20 million published citations on PubMed, and a proper search needs to be designed, which includes search terms, application of limits, and performing a title review, followed by an abstract review, and the acquisition of key full text articles for details, including study methods, data for power calculations, and reference mining for additional articles.
In some cases, interviews are required with Key Opinion Leaders (KOLs) in specific therapeutic areas. In special situations (such as pre-IND meetings or when evaluating potential control therapies for study products that cannot be blinded), regulatory agencies may be contacted for their input.
At the end of this process, all notes and findings from the meetings, conference calls, questionnaires, data review, literature search, and our own experience and internal database are evaluated and synthesized to select the best possible elements of the study design, including objectives, endpoints, populations, inclusion and exclusion criteria.
Additionally, there will be input on dose selection and statistical calculations, based on prior studies, to determine the appropriate statistical analyses to be used in the study and to create a statistical analysis plan. The analysis plan is an outcome by outcome, endpoint-by-endpoint, table-by-table, figure-by-figure detailed document, which will be the basis for the statistical analysis.
There will be more than 100 different documents, including the study protocol, ICD, logs and forms. Scales and questionnaires require permissions from their respective authors and copyright holders.
Medicus Research is the only company that creates step-by-step customized standardized source collection documents, which match the protocol and the data collection requirements, as well as completely standardizes the process by which the data is collected to ensure standardization between subjects, research coordinators, investigative sites, and even between countries.
All documents go through a multi-step internal QA/QC procedure by which they are reviewed for consistency against the study requirements, the protocol, the statistical analysis plan, and for spelling and grammar. A secure intranet location is set up for each study, and all required documents are stored there with limited permissions-based access for personnel on an as-needed basis. The clinical trial management software (CTMS) is customized for the study and all recruiting, appointments, and tracking occur through this specialized software base.
The regulatory approval process involves the IRB/Ethics Committee, and, when required, the FDA. The IRB approval process requires a 20-page detailed application for the study and for each investigative site. The application includes submission of the protocol, ICD and a board review containing questions to be answered. Creation of regulatory master files for the entire study and for each clinical research site are developed and maintained (the original is kept at the site along with a shadow file kept at the CRO).
Clinical Research Sites are identified, interviewed, visited, and evaluated for their ability to recruit and enroll subjects, but also for their ability to collect high quality data, to treat their patients with respect, and to have an open mind when dealing with natural health products.
We interview principal investigators and select doctors who will be open to these products. We choose doctors who will not be biased against the investigational products that they introduce a negative preconceived notion in their subjects, nor so zealous in favorer of the products that they influence a positive bias.
Contracts and budgets are negotiated with each site before their IRB application is submitted.
Project management workflow is set up using project management software. A risk analysis is performed to determine the particular risk characteristics, including environmental, medical, personnel, financial, political, and regulatory risks that can introduce delays or problems.
As Medicus Research is a global company, we have dealt with earthquakes, strikes, study product manufacturing delays, and unusual flu seasons among other issues. We assess the possible risks in advance and create contingency plans to mitigate those risks.
A subject recruitment plan is formed, and we proceed with the creation of recruitment materials (including translation into appropriate languages), submission of recruiting materials to the IRB, training our call center personnel on the study requirements, launching the phone system for the new study, setting up tracking logs, and negotiating with vendors. All comprise an essential aspect of the recruitment process.
Recruitment marketing includes, but is not limited to newspaper, television, radio, Internet and community outreach (such as health fairs, meetups, universities, organizations, malls, clubs, and local community groups).
Financial modeling is performed for the study as a whole and for each individual research site. Payment milestones are entered into the project management system and tracked to ensure adequate monetary flow in all directions throughout the course of the study.
Laboratory test requirements are determined based on the protocol, and an RFP is sent to preferred vendor labs. For new or uncommon tests, reference labs across the country, including academic labs, are contacted and evaluated. Test methodologies are obtained and scrutinized and, where required, on-site visits are made to ensure Good Laboratory Practices (GLP) methods are being followed. Individual laboratory test requirements are obtained and verified, including collection, processing, storage, and shipment requirements. Lab collection, processing, and storage kits are created for each visit of each study and are shipped to each clinical research site.
Study specific inventory requirements are assessed, including specimen collection supplies, lab kits, food, medical equipment, rescue medication, testing supplies, and IT hardware. These supplies are managed throughout the study with automatic threshold reorder points created so that the initial and replenishment shipments occur on time.
An Investigators’ Meeting is conducted for all of the investigators in the study. This can be an on-site meeting or a virtual web meeting, during which the following topics are covered:
- Background on the investigational study product;
- Background on the therapeutic area;
- Protocol review, including a review of the inclusion/exclusion criteria;
- Protocol activities;
- Study product dispensing;
- Source document/CRF completion guidelines;
- Logs/binders/forms completion guidelines;
- Supplies and inventory;
- Adverse event reporting guidelines;
- Recruitment strategies, and timelines.
A Site Initiation Visit (SIV) is also conducted to confirm and validate the site’s readiness to begin screening and enrollment, while bringing all personnel involved in the various aspects of the study together.
A monitoring plan is created and scheduled based on estimated enrollment at each site. The monitoring codebook is created, along with edit checks and events of clinical interest. The monitors are trained on the study, including all of the details reviewed during the investigators’ meeting. The monitors introduce themselves to the study site and establish a relationship that fosters communication.
The investigational study product requirements are calculated and sent to the sponsor. The study product labels are printed and sent to the sponsor for packaging. The cold chain is set up so that all study products are tracked and temperature controlled through every step of the transport process. When the study product arrives from the sponsor, it is inventoried and locked in a highly secure double-locked, temperature-controlled storage room. Every study product movement (to and/or from any location) is documented and logged in the study product accountability binders. Test samples of the study product are sent to third party laboratories for testing to ensure that there is no adulteration or contamination. If necessary, the study product is encapsulated, bottled, and/or labeled in our pharmacy.