Source: Life Science Leader, by Leeann Ali
Startups and small companies are crucial to the development of breakthrough drugs and therapies, but with limited capital it is essential that they move quickly and efficiently during clinical trials to maximize the potential for successful outcomes.
Designing and executing a clinical trial requires juggling many complex moving parts and stages, and it is easy to get tripped up. Issues with safety, manufacturing, participant enrollment, and the challenges of lab sample and data analyses are all common sources of failure.
Having a clearly written plan that involves proactive management — including regular progress reviews — can help ensure that the right partners are involved, accurate data are collected, and that the trial meets all regulatory requirements. Fortunately, trial sponsors can lean on expertise from the federal government. Regulatory agencies provide superb information to guide the development of early-phase clinical protocols. Certain Phase 1 protocols can be derived from ClinicalTrials.gov, for example, and can serve as a template for medical writing purposes.
There are hurdles when the study design is conceived, and those challenges are compounded when clinical protocols are put into action. It takes considerable funding, resources, and time to begin and complete a clinical trial. Here are seven areas that sponsors can focus on to achieve success:
1. LIMIT OPERATIONAL DEPENDENCIES WITHIN YOUR ORGANIZATION
As soon as possible, limit the dependencies of your activities to speed up the completion of events that will lead to the first enrollment. For example, a sponsor can simultaneously submit the development plan to a local ethics board and the IND plan to the FDA; this is called “submitting at risk.”
If the FDA requests changes to the protocol, the modifications can be woven into another submission to the institutional review board (IRB) after its initial review. However, if there are no significant or material alterations to the safety profile, the updates can be reviewed in an expedited fashion.
2. SPEND TIME TO RESEARCH YOUR STUDY PARTNERS
Sponsors should thoroughly screen and confirm vendors and suppliers that will be involved in the study. The process of vendor selection is a topic unto itself, but it is important to have technical — and cultural — alignment with all companies that will impact the execution and reporting of the study. Ideally, select your vendors at least three months before the first patient or subject receives treatment.
Having a strategic vendor-selection process can be a difference maker when it comes to the study — as it should be because your organization’s reputation is at stake. Smaller companies do not benefit from preferred provider relationships, while employees from bigger companies may not consider their vendors to be “preferred.” (Note for small companies: If you are looking for a thought partner or SME who can provide invaluable advice and help make decisions to drive study execution, you may need to ask and pay for the involvement of the vendor’s senior management.)
3. IDENTIFY WORK THAT CAN BE PERFORMED BEFORE IND SUBMISSION
Once vendors are selected, decisions need to be made about how much advance work they can perform prior to IND submission. Execute a contract too soon in the process, and you’re likely to go out-of-scope before the first enrollment. If your budget can tolerate a contingency margin, then this may be an effective way to ensure your study is resourced. If it is decided to begin all vendor activities once the protocol is submitted to the agency, then between 14 and 20 weeks should be factored into the research timeline.
In many cases, sponsors ask vendors to assign a team and then begin work after there is a final synopsis, but before there is a final protocol or executed master services agreement and budget. Many vendors will begin work only after completing a signed letter of intent, so the sponsor needs to be strategic in determining which parts of the trial are likely to change before the first test participant is enrolled.
4. HAVE YOUR PARTNERS START BUILDING DATABASES EARLY IN THE PROCESS
Some vendors and CROs will begin building their databases based on a synopsis, and it is a good idea to ask for this to occur whenever possible. CROs have a library of standard data forms, such as medical history, demography, and adverse events, that can help accelerate the time required to create the initial database. Building the databases as the protocol is finalized will save significant time because it allows systems to be validated and ready for patient data.
The same strategy holds true for pharmacovigilance, sample management, and specialty lab vendors. Vendors can begin setting up their internal systems and ordering supplies upon receipt of a final synopsis or draft protocol. Ensuring adequate supplies, such as reagents and sample collection tubes, can be especially challenging during a pandemic. Your vendors are critical partners for study execution, and it is important to ensure all parties are aware of the internal and external timelines that are the basis of their activities.
5. KNOW THE INTERDEPENDENCIES AMONG YOUR VENDORS
Achieving each milestone within the trial is dependent on the successful performance of many contributors. Whether the study is being conducted at a Phase 1 unit or in multiple clinics and countries, it is important to understand the interdependencies of your vendors. Lab samples need to be properly collected, accessioned, shipped, and analyzed before data and safety monitoring board (DSMB) meetings. Data transfers must be conducted in a timely manner to enable data analysis.
Developing and maintaining a master timeline — and identifying the interactions of your vendors — is critical to the success of the trial. During the timeline’s development, sponsors should challenge assumptions within each vendor’s timetable. Once developed, each should be reviewed at least weekly to ensure all subactivities are being conducted in a timely manner.
6. BE PROACTIVE IN OBTAINING FEEDBACK FROM VENDORS
As enrollment commences, sponsors should be vigilant in seeking feedback from all vendors. If there are challenges in filling a cohort, for example, the team may need to meet to determine whether it is an issue that can be addressed via training, a protocol amendment, additional recruitment activities, or opening more sites.
Sponsors should request specific information from their vendors when there are operational challenges. Vendors should be told to be “solution ready” when identifying issues during the study. The team may need to revisit their assumptions to determine whether environmental factors, such as competing clinical studies or a global pandemic, necessitate changes to the timelines.
7. REVIEW YOUR CLINICAL DEVELOPMENT PLAN TO EVALUATE WHETHER ADJUSTMENTS SHOULD BE MADE
Finally, sponsors should periodically revisit their clinical development plan after the start of the first study. Sponsors may achieve their primary endpoint before enrolling all cohorts, for example. This information could accelerate the initiation of additional clinical and non-clinical activities. The team needs to be prepared to make decisions relative to the use of the unused resources to potentially accelerate or modify their registration plan.
The first participant in a clinical trial is a watershed event for every development program. It is the culmination of hundreds of small decisions. The road to commercialization begins with careful planning and successfully completing the first clinical trial — and incorporating these strategies and tactics can increase the odds of introducing a new drug or therapy to treat patients in need.
LEEANN ALI is VP of clinical-regulatory development and is a principal consultant with BioBridges. She has more than 28 years of clinical operations experience with startups, large pharma, and CROs.
BioBridges provides clinical development services to emerging and established pharmaceutical, biotechnology and medical device companies. Since our inception in 2005, we have designed and built our proprietary and scalable Career Portfolio® Management model, which engages our professionals to meet the specialized needs of our clients’ clinical programs. This model has stood the test of time in our work with over 500 companies since our founding in Cambridge, MA. Today, we serve a national base of clients around the U.S. with our highly skilled professionals as we collaborate with our clients to advance science and produce therapies for patients who need them.
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