Bringing your product into clinical develop, and successfully conducting clinical studies, relies on a plethora of factors in addition to a strong, differentiating scientific and clinical rationale. Challenges often include locating funding and forging industry partnerships, and maintaining adequate dialogue between regulatory agencies, clinicians, patient advocacy groups and payers. Each aspect plays a vital role in conducting a successful clinical program. This can seem daunting if you do not already have contacts or past experience to lead with; in such cases a specialist consulting firm can be a highly beneficial partner on this journey.
Preclinical development explores how the product behaves in various different animal models, each gradually increasing in complexity and scale with the aim to predict how the product might perform in human systems. The results of preclinical assessments will provide investigators with information on dosing, toxicity, safety and an expectation of how the drug is metabolised. The next step, translational medicine, is the process of translating findings from these animal models into human clinical trials.
However, it’s worth noting that for some programs it might not be appropriate to perform extensive animal testing. For example, if there are no reliable animal models in existence for the indication of interest then limited animal studies may be used to explore safety, with efficacy only explored as part of human studies. This poses an obvious challenge in translating bench research into bedside treatment, and early dialogue and clarification from experts and regulatory agencies is recommended for such programs.
Moving into human subjects is far more complex, more expensive and more tightly regulated then that of animal testing. Given the additional cost, this is often the point in product development where outside investment, or industrial partnerships, are sought. Bringing any investor(s) into a program has the benefit of not only providing money, but also providing expertise and access to clinical networks, if the right investors are selected.
However, locating appropriate partnerships is a competitive task, and often requires extensive market research, risk assessment and valuations of drug programs to create a compelling and clearly defined opportunity for investors. You will need to develop landscape insight, which requires evaluating market dynamics, evaluating objective competitive data, investigating patient pathways, and conducting research into unmet needs in the evolving market. Providing evidence to support good integration into clinical practice, in addition to considering pricing and reimbursement strategies, is also important. The key value points identified in a given drug program should be well represented in the endpoints of clinical studies.
Once funding is secured, or indeed alongside obtaining funding, you can move into the clinical testing stages. Clinical Trial Authorisation (CTA)/Investigational New Drug (IND) approvals are given by drug regulatory agencies and are required before a clinical trial can commence. To gain approval, developers must submit dossiers to selected Agencies (dependent on where the trial is being held) and await their feedback. The process of approval can be highly variable across countries and agencies, and is a challenging aspect of conducting clinical trials. Providing Agencies with high quality and thorough clinical trial documentation is vital in moving smoothly through the clinical pipeline; it can be beneficial to have documentation reviewed by an independent party prior to submission for review.
The clinical trial protocol should be created in collaboration with at least one expert clinician. The clinical protocol will describe in detail, every aspect of each trial, including:
- Preclinical rationale
- Trial design i.e. patient numbers and grouping, trial sites, duration, data collection and storage, statistical analysis
- Translational medicine i.e. dosing schedule
- Regulatory reporting
- Clinical endpoints to measure the toxicology, metabolism, safety and efficacy
In helping form each of these sections, considerations need to be given to practical factors such as patient access and product manufacturing. Often healthy volunteers are used in first-in-human (FIH) studies, which are recruited by advertisement with subjects being paid to take part. However, recruiting patients into trials can be more challenging, particularly for rare diseases. Considerations must then be given to your trial design and statistical analysis, particularly for the bigger Phase II and III trials. Working with patient advocacy groups is a good way to increase access to patients, as is tapping into clinical networks to encourage physicians to refer patients into trials. This aspect will also play into site selection for the trial and can add additional cost.
Once your trial has been approved by the regulatory agency in the selected territory, approval must now be sought by the Institutional Review Board (IRB). This review will focus on the ethics and patient welfare, and will perform a risk-benefit analysis at clinical sites. And finally, once all sides are approved, the trial can begin.
A key aspect of running an efficient and effective clinical trial is good communication between the sponsor team, clinical personnel, regulatory agencies and patients. This can be challenging to handle, and some companies commission contract research organisations (CROs) to manage the day-to-day running of a trial, although this is another additional cost.
The overall process of getting a product into the clinic is a highly complex process and always unique to the product in question; above, only a handful of the obstacles involved have been discussed. Support from an external, multi-disciplinary team with clinical expertise and commercial awareness is highly beneficial in providing unbiased support throughout your journey from bench to bedside.
Life science consulting firms are often the best source for such support. It is important to recruit a firm with proven clinical experience, with expertise not just in clinical development as a whole, but in specific indications and particular product types.
For example, Alacrita is a transatlantic consultancy firm with experts, and in-depth experience, in every aspect of product development. A selection of areas that consultancy firms can support includes:
- Validating whether you have enough data to enter into clinical studies
- Establishing whether there is a profitable market for the product based on market research on epidemiology, the competitive landscape and current standard-of-care
- Valuing the product, and identifying the most appropriate pricing and reimbursement strategies
- Identifying funding sources and industry partnerships
- Developing, or providing support in developing, clinical documentation
- Interacting with regulatory agencies
- Providing on-site medical or operational support
In summary, for a successful clinical program, you’ll need to marry clinical and commercial intentions, meet stakeholder requirements, optimise your execution and operations and ultimately deliver value to all beneficiaries.
‘*By Jess Hearn, Alacrita Consulting Inc;, Cambridge, Massachusetts’*