Conducting clinical trials is an effort-demanding mission, requiring various specialized skills. The basics on which it stands is compliance with GCP guidelines and local regulations, adherence to sponsor guidance documents and company SOPs, all this while guarding study-participants safety and well-being as well as maintaining high quality data.
The specialized skills required by professionals in the pharmaceutical industry constantly demands knowledgeable and qualified staff at all levels.
At Q-Trials, we believe that good training programs ensure all employees and vendors are knowledgeable, qualified and well prepared for their roles.
All employees and major vendors must undergo training on several levels on a constant basis. All training needs to be documented and signed and dated by trainer and trainee, filed appropriately.
New Staff Training
All new employees begin with basic, on boarding training per their designated role. This includes primary orientation, company instructions and procedures and project specific guidelines. These may be performed through review of relevant documents, power point presentations, e-learning systems, or live webex.
One-on-one mentoring is another form of training characteristic to on boarding phase. It includes individual training according to role and project within the company and is done through face-to-face meetings, on site co-visits, and on the job demonstration, where monitoring skills and project specific training are obtained.
Job specific training
Relevant employees and vendors are trained according to their role on an ongoing basis per their job requirements, changes and updates.
Staff is trained on specific projects as per company SOPs, self-review of documents, investigator or CRA meetings, and teleconference joining.
Company SOPs Training
Q-trials quality system is maintained through its set of procedures, which is reviewed and updated on a periodic or ad-hoc basis following which all employees and vendors are trained upon.
Team training is performed by the company during periodic, usually monthly meetings. Training sessions are performed by one of the employees on a particular pre-selected topic, or by an external lecturer. Participation is mandatory.
A periodic 1-day GCP refresher training is mandated for all employees in the company, regularly held yearly or bi-yearly.
Circulars and regulatory updates are sent to all employees on a routine basis via email as they arrive.
Accompanied monitoring visits (AMV) are used to assess CRA performance during an on-site visit. It is also a tool for training the CRA by the assessor, where monitoring, communication and other skills are reviewed.
In summary, we at Q-trials believe that continuous training is an essential part of excellence and a key tool for high performance in our company. Moreover, it enables Q-trials to keep up with new regulations, sponsor requirements changes and internal policies updates. All level training supports organizational as well as individual growth in this ever competitive global environment.
The new upcoming International Conference on Harmonization (ICH) Good Clinical Practice (GCP) E6 (R2) addendum represents the biggest change for this important guideline since 1996. Significantly influencing clinical trials monitoring and management, it is likely to take effect later on this year (2016).
The current ICH GCP Guideline was finalized under Step 4 in May 1996. It describes the responsibilities and expectations of all parties participating in clinical trials, including investigators, monitors, sponsors and IRBs. To complement the ICH E6 Guideline, published in May 1996, the new addendum’s purpose is to modernize ICH E6 and "to encourage implementation of improved and more efficient approaches to clinical trial design, conduct, oversight, recording and reporting while continuing to ensure human subject protection and data integrity.”
One of the more significant changes represented in the new GCP guideline is the Principal Investigator (PI) oversite. The Principal Investigator roles are more clearly defined in regards to their responsibilities conducting clinical trials.
The PI has the main responsibility for the design, conduct, and management of a clinical trial. He presents the study to the review board, manages the study throughout its course and the patients are his or hers. Although there are other staff members participating in the conduct of the clinical trial, with delagated tasks, the overall responsibility is his own.
We can see that the Investigator responsibilities are relayed in more detail and emphasis, particularly the following areas:
Delegation of tasks. This clause requires the investigator to supervise those team members to whom they delegate study tasks conducted at the trial site.
Team qualification. This clause requires the investigator to ensure that the team members are qualified to fulfill the assigned tasks and implement procedures to ensure the integrity of the study tasks performed and any data generated.
Source documents. This clause requires the investigator to maintain adequate and accurate source documents and trial records that include all patient observations on each of the site’s trial subjects. Source data should be: attributable, legible, contemporaneous, original, accurate, and complete.
Essential documents. This clause requires that the investigator maintains a record of the location of essential documents.
In summary, it is essential that there is clear, documented evidence of the PI's oversight and involvement in the clinical trial.
Only time will tell if this important subject will indeed change due to regulatory requirement or will clinical trials remain the domain of the SSCs and CRAs.
Prior to the initiation of any clinical trial and making strategic decisions regarding what countries and which sites are suitable for the particular area and population of research, a thorough investigation of the situation on grounds is required.
This choice can make the difference between the success or the disappointment from the research endeavor. Country feasibility is particularly important, as countries vary greatly in regulatory restrictions and timelines, and sites can vary greatly in their resources and capabilities to deliver.
The relatively small investment and effort can yield significant information early on, saving huge costs. Avoiding non solid assumptions and surprises in the midst of a trial could yield a smoothly run, well conducted trial.
Over the years, Q-trials performed numerous country and site feasibilities in a wide variety of indications and has developed a systematic approach to performing this task.
Here are some tips to the conduct effective feasibly studies:
Designated Person. Designate a person, preferably familiar with the indication and with potential sites for the task. Prior experience conducting such tasks is an advantage to the allocated person.
Set of Tools. Make sure you have everything you need to kick off the feasibility task: confidentiality agreement template, protocol synopsis (at minimum), feasibility questionnaire, list of sites or investigators favored by the sponsor. At times, a Sponsor might not have acquaintance with the investigators in the country, so this requires your input on who to approach.
Timelines Planning. Timelines are usually aggressive in feasibility studies and need to be strictly respected. This can place limitations on the number of investigator sites contacted, or on the choice of specific personnel that can be reached (i.e. not someone currently out of the country) so pre-planning and quick adjustments are key.
Self Knowledge. Review study protocol as well as Sponsor specifications and questionnaire thoroughly. Also Sponsor or Q-trials SOPs on feasibility conduct should be checked prior to any action taken. Questionnaire may to some extent be adapted according to local requirements and regulations.
Risk Anticipation. Try to see beyond the scope of the questionnaire and, based on the protocol requirements, investigate additional questions if you identify unanticipated risks that could evolve.
Local Regulatory & Site Familiarity. Knowledge of local regulations and the specifics of the local sites are paramount. Discuss with the sites any specific and/or known barriers potentially imposed by the study requirements.
Investigators Database. maintain a list of key opinion leaders in the various specialties in order to facilitate fast information gathering. Seek additional information as you approach and interview other investigators to widen that list.
Follow up Spreadsheet. Create a study feasibility spreadsheet and insert the dates of contact, follow ups and follow up information for each investigator site. Include comments where relevant.
Confidentiality. Agreement (CDA) must be in place prior to disclosure of any confidential information. Make sure you receive fully signed agreement by the approached site(s)’ investigators on the pre-prepared confidentiality agreement. Any holding of such signatures or doubts on authorization to sign may pose delays and additional burden, therefore consider abandoning sites that don’t respond quickly and be prepared to pick others instead.
Questionnaire Completion. Send out the feasibility questionnaire along with synopsis immediately following receipt of the executed CDA without delay stating timeline expectations. Follow up on receiving it back as completed and as soon as possible. Review returned documents and make sure you understand what is written. Get back to the site with questions or missing information without delay and before forwarding results to Sponsor.
Meetings. Where a meeting needs to take place, meet the investigator and any other relevant site staff such as study coordinator. Interview them according to the questionnaire. Ask for a tour of the facilities and a view of their electronic systems and data bases. Collect any wet-ink documents such as CDA and CV where possible and relevant.
Asses Recruitment. Potential recruitment assessment is particularly important, however it is useful to note that the numbers are sometimes over exaggerated and it is better to have a more conservative approach. Discuss this with the investigator sites. Try to reach not only the investigator him/herself but also other staff members such as study nurse/coordinator. Ask if they can truly stand behind the numbers and deliver. It's important to consider whether the presence of the suitable patient population also means relevant access to the population for the clinical trial.
Environment Review. Ask about competing studies, the stage of these studies, differences in study population requirements, payments received for the competing studies or other incentives.
Budget Assessment. Know the costs in advance by clarifying ahead with the sponsor. This issue almost always comes up during preliminary discussions. Countries and sites might differ in cost requirements per study or per patient. In addition, sites could have different approval timelines and contractual requirements. Be as specific as you can about these topics and eliminate sites that are far off the Sponsor scale n this respect. Avoid negotiations at this point and merely convey the information on budget. Ask for reasoning to higher than offered costs and present this to the Sponsor. There might be room for negotiation from the Sponsor's as well site side.
Results Submission. send back to Sponsor a neat package containing signed CDAs, completed questionnaires, filled out spreadsheets and any comments you may have before or by the stated deadline. Accompany with an email detailing all included items attached and any special comments you would like to highlight. Copy in everyone that was on the original request for feasibility, preferably chaining your response to the original email.
Pairing up with a knowledgeable and experienced CRO will help you navigate the maze of the country and site feasibility, effectively and accurately. We are available to discuss further on how we can help you achieve your goals.
Quality is a parameter that cannot be overestimated in the field of clinical trials. Clients, Medical professionals and ultimately the patients, depend on our high quality work hence this is not to be taken lightly.
Many small companies strive to achieve and maintain a high level quality system while balancing the constraints of running a smaller business at the same time. We, at Q-trials, are firm believers that this is possible to accomplish, although requires some investment and effort.
Here are some of our tips on how to achieve this:
Process owner: for each SOP identify the most experienced process owner, ask them to write down their steps (or interview them), in chronological order, as if they are guiding someone who is inexperienced in this field of work.
External consultant: when required, and every once in a while on a regular basis, contract an external expert consultant. The right consultant would be able to look at your quality processes with fresh eyes and bring a perspective to the table that you might otherwise overlook. It’s an investment that will pay back and will ultimately improve the functioning of the company.
Processes administrator: nominate someone from the staff to oversee the quality processes. At Q-trials, we have a part time Processes Administrator who is responsible to ensure that the company is compliant with its quality procedures.
Realize the need: every company working in the arena of clinical trials is required to have and maintain a quality system of its own. Start constructing your quality system on a limited scale using your best tools, knowledge and experience available.
Keep it simple: limit your formal quality system (SOPs) to GCP related topics and form policies for internal matters that you would like to follow.
Market: take your written procedures seriously, encourage your staff to review before important tasks are done. This approach contributes to the increased sense of responsibility and the pride for the work done well. Standard operating procedures are not just something to read once and check off the list, but the go-to manuals for the day to day activities.
Logistics & Technicality of Quality Documents
Format of quality documents: establish or adopt a format and use it consistently throughout your writing process.
Language: you may use local language, although English is handy for international parties review and audits. Use basic terms and brief sentences.
Filing: file your SOPs in an accessible location, enable review only mode, discard of old or non-relevant SOPs in an acceptable fashion.
Review: upper management should independently review and comment on the written procedures. Perform several rounds if needed, before finalizing and signature.
Training: conduct centralized or self-training within the company. While it’s important to hire people with certain skills and qualifications, develop a robust internal training program. This will ensure that all employees are trained according to the same high standards. Part of the onboarding training for new employees at Q-trials is the thorough review and acknowledgement of the set of relevant SOPs. In addition, facilitate pairing up with an experienced team member, who ensures the training process is completed correctly and gives immediate feedback to the starting employee.
Audit yourself: initiate periodic self-audits of your quality system, or choose a sub-set of SOPs in a certain area for objective inspection. Complacency is the enemy of quality. It’s important to conduct periodic checks of the systems that usually result in improvement of actionable items that we work on continuously.
We believe that constant self-inspection and checking ourselves is key for further improvement and opportunities for learning how to do things even better.