From planning to completion, clinical trial development deals with a large number of very narrow speciality fields. For small biotech companies, the task of connecting and enlisting with experts on each one of these fields can pose a significant challenge - especially as different individual trials may altogether involve new specialties or patient populations into the table.
Yet, the input provided by experienced medical consultants can have a deep impact on a trial’s future success. The gains in efficiency and expediency brought on by these experts need to be balanced with the potential budget benefits of keeping the process in-house.
In this article, we will delve deeper into the key stages in the development process where scientific and medical expertise is often required, as well as the specific processes where it makes the biggest difference.
The clinical development stage will require committing the necessary resources for a clinical trial. Before this can be accomplished, it will be necessary to develop a product that can attract investors.
To develop a robust clinical trial plan, there are several key processes where outside clinical expertise can be of special value for small companies.
First, it will be necessary to define the indications of any new investigational medicinal products (IMPs) and the size of the potential market that would use them. In turn, the indication will help determine what types of studies will be needed to ensure the eventual approval of the drug.
Often, pre-clinical development of new drugs is created “with the end in mind”. While the end goal will be to have a safe, effective drug approved, this approach often creates a gap between the results of pre-clinical trials and the data needed to develop an appropriate protocol for human trials. \(^1\)
At this stage, enlisting the help of experts who have dealt with similar IMPs can help.
For a new drug to be commercially viable, it will need to show itself to be useful among two key audiences: the patients who would use it, and the doctors who would prescribe it.
It is important to look at both sides of the clinical setting when designing a new product. Will the physicians consider the drug or intervention to genuinely help the patients? Will the new medication be necessary? Moreover, will the patients feel they are benefitting from switching to a new drug?
An appropriate strategy can help shorten the times required to get all the approvals from the necessary regulatory agencies. In turn, having evidence of being on track with any applications can help generate additional interest from investors.
Central to any protocol is a series of issues regarding the way the new IMP is meant to be used. Note the dosage regime, and that of any control groups, need to be appropriate for the drug’s pharmacokinetics.
A pharmacology expert can also help determine which dosage will offer the best chance at showcasing the full potential of the investigational product.
The development of a trial protocol will require a multi-disciplinary approach. Here, outside expertise will have the biggest impact when designing pharmacological indications and when performing statistical analysis. In addition, further valuable information can be gained by consulting with medical experts in the field that the IMP will target, as well as from the target patient population.
A key element of clinical trial implementation lies in determining the right sample sizes. This field can be especially challenging for trials that aim at orphan indications or rare diseases. The trial will need enough patients to demonstrate efficacy, without setting unrealistic recruitment targets.
In such cases, it will be necessary to consult with a medical consultant who has experience in rare diseases, or existing relationships with patient associations or advocacy groups.
The services of an experienced medical writer are in constant demand throughout the entire product development process. The types of documents handled by medical writers have also expanded, just like the knowledge required to tackle them properly. For example, protocol development requires a different set of skills compared to working on scientific publications.
This has led to an increase in subspecialties within the medical writing field. Often, a single medical writer cannot handle every document throughout a clinical trial’s work cycle. Instead, these services are increasingly provided by medical writing agencies.
The clinical trial start-up phase is often the most complex, and almost always the most onerous phase of a clinical trial. At this point, help is usually needed to set up functional plans like the recruitment plan and International Standard on Quality Management (ISQM) plan that will prevent delays and keep the clinical trial on budget.
During the study start-up phase, external help or outside expertise is usually required to design the training and processes that will keep the trial running later on. This includes the following:
The clinical trial plan and protocols designed so far will need to be brought into reality. The ability to do this, and the way the different plans sync together, will be assessed by the feasibility group.
Expertise in Risk-based quality management (RBQM) is a relatively rare skill set. Yet, designing these processes effectively from the start will allow for cost-effective and sustainable quality monitoring processes throughout the trial. Furthermore, once the trial is ongoing, best practices suggest implementing additional centralized monitoring processes. This will improve the quality and traceability of any data submitted to regulatory bodies.\(^2\)
By design, an effective Safety Monitoring Board of Committee should be comprised of a group of independent experts. Although not all trials require one, both the FDA and the EMA recommend setting up such a committee for any trials that may carry significant safety issues.\(^3\) The decision of whether a Safety Monitoring Board is necessary carries a lot of weight, both for trial completion and for final approval.
Similar considerations should be given to assessing the need for the development of a Safety and Medical Monitoring Plan.
Study-specific training often plays a key role in ensuring a smooth start-up process for any clinical trial. For multi-site projects, product-specific training will also help ensure that the same procedures are uniformly applied at all locations.\(^4\)
However, the process of designing training materials, or of conducting the training sessions (whether in person or virtually) is usually a time consuming one. Because of this, developing training modules in-house is often infeasible for smaller companies. CROs are usually able to offer this service as part of study start-up services, or throughout the execution of the trial.
Once a trial is undergoing, the systems and feasibility studies commissioned during the planning stages should bear their fruit. However, three critical areas will require ongoing monitoring:
In addition, it is important to nurture the patients enrolled in the trial. This will increase their level of compliance and keep them from dropping out of the study. Here, additional enrollment liaison management practices may be necessary. An expert opinion can be sought to study the enrollment on each site or country where the study is taking place.
At the post-registration phase, continuous monitoring will continue taking place, especially for Safety monitoring, or to explore the possibility of developing new indications
The figure of the Medical science liaison has been growing in importance within the pharmaceutical industry, for both large and small companies alike. For trials dealing with niche subspecialties, such as infectious diseases.
A growing industry trend is to outsource the recruitment of medical science liaisons.\(^5\) This is partially driven by the increasing difficulties of accessing KOLs in many fields. Yet, the feedback of KOLs continues to be invaluable, especially for post-study activities such as publication or when filing for a marketing authorization application. The networks required to approach KOLs or medical science liaisons are usually built over decades.
As a project management organization, Dokumeds has been operating in Europe since 1995. Dokumeds supports mid-sized and small biotech or pharmaceutical companies through the different stages of preparing and managing a clinical trial. Dokumeds’ deeply-established network allows to provide scientific advisors for protocol development, involve Key Opinion Leaders, and undertake feasibility studies. Dokumeds can also provide management and medical support to assist with clinical operations, monitoring, and medical writing.
When clients request it, Dokumeds can evaluate and contract third party service providers and additional experts to support the client during their product and program development.