By Naveed Panjwani, Director, and Cian Fahy, Senior Consultant, Deloitte
Deloitte’s annual report series, ‘Measuring the return from pharmaceutical innovation’ has demonstrated that the cost of conducting clinical trials has, on average, increased year-on-year and, for the most part, the average returns that pharma companies can expect to realise from this investment have declined.1 As global pharmaceutical companies increasingly focus on streamlining and reducing the associated costs and timelines of the clinical development pathway, they have largely focused on actions to reduce the more expensive late-stage processes. In this week’s blog we discuss some of the opportunities for improvements across the earlier stages of the clinical trial process.
Why early clinical development trials?
The traditional, linear and sequential clinical trials process, that on average takes 10-12 years to bring a new drug to market, has remained the accepted way to ensure the efficacy and safety of medicines for decades (see Figure 1). However, the availability of increasing amounts of scientific and research data from a variety of sources, and AI-enabled technologies to make the most of this data, have led to pharma companies reviewing their approach to improve the efficiency and cost-effectiveness of the clinical development process.
Figure 1: The traditional clinical trial timeline and lifecycle
Source: Deloitte analysis, 2023
In trying to identify improvements, an often-overlooked area is that of the early-stage clinical development (Phase I and II studies; see Figure 2) where organisations have a unique opportunity for efficiency enhancements to improve the journey to proof of concept and achieve earlier ‘go or no-go’ decisions when compared to late-stage development (Phase III and IV studies). These earlier stage trials are typically smaller in scale with fewer participants and are conducted across a smaller number of sites and geographies. This creates a less complex environment for experimentation with new innovative operational, technological, people, and scientific approaches to understand disease progression and simplify clinical trial execution. Initiatives that are implemented during the early stages of clinical development will also enable downstream streamlining in late-stage clinical development phases.
Figure 2: Key activities across early-stage clinical trials
Source: Deloitte analysis, 2023
Common pitfalls and opportunities for simplification in early clinical development
Table 1 below summarises the common challenges and consequent opportunities for organisations to streamline the management of their early-stage clinical trials. These improvement opportunities range from areas such as protocol development & planning, recruiting the first subject (FSI), and study decision-making procedures.
Table 1: Summary of challenges and opportunities for improving management of early-stage clinical trials
Opportunities for simplification
Inadequate consultation with external stakeholders (e.g., key investigators in the disease area, vendors for labs & devices, and clinical research organisations) during early planning stages leading to sub-optimal study design aspects (e.g., scheduling of assessments, data review requirements)
· Rigorous development of a biomarker strategy and operational plan coupled with early engagement with key opinion leaders and vendors to ensure that the strategy is scientifically and operationally viable.
· Collaboration with CRO partners to gain buy-in for the overall trial plan can ensure that the CRO is aware of trial complexities and resourcing needs for timely execution of the plan.
· Early engagement with regulators around digital end points and technologies being piloted in the trial.
· Mapping of the patient journey during the trial to identify opportunities to improve the patient experience.
Application of late-stage trial
thinking and procedures rather than specialised early-stage development knowledge and expertise leading to delays in study start-up
· Establishing an early-stage clinical development Centre of Excellence where institutional knowledge across programmes is stored and shared for teams to leverage templatised and predictable processes during early-stage clinical development.
Lack of early planning upfront to include information around dose escalation strategy, digital strategy, biomarker development, and proof-of-concept scenarios leading to uncertainty in decision-making during trial conduct
· Developing a templatised approach to planning key aspects of the early-stage clinical trial including detailed information around the decision-making criteria, trial endpoints, biomarker and tech strategy can help organisations identify risks earlier and trigger mitigation strategies.
Tentative study design that is prone to frequent amendments which in turn cause downstream delays and cost implications with study start-up activities
· Developing a rigorous protocol synopsis with a stable schedule of assessments and operational study plan based on early engagement with internal and external stakeholders allows the study teams to identify long-lead time activities, socialise the study design CROs, vendors, and regulators, and minimise changes to the protocol post-approval.
· Early confirmation of study design can help identify activities at risk and minimise delays in study start-up and site activation for first subject in.
· Piloting risk management and analytics tools can help streamline decision-making and support expansion of these frameworks to next phases of clinical development.
The lack of access to unified data across labs and electronic data capture systems inhibits inflight decision-making
· Piloting technology solutions to aggregate and identify near real-time listings from raw data can enable faster decision-making.
· Piloting large language models to summarise key issues and results can accelerate go-no-go decision making.
· Clearly documenting criteria for interim analyses (including in-scope data elements) can help teams prioritise the cleaning of the data for decision making.
Unclear documentation of go-no-go criteria leads to delays in decision making to progress candidate into next phase of development
· Documenting the primary and exploratory criteria that will be used to progress candidates into the next phase as part of the early-stage clinical development planning can help mitigate delays in decision-making post-study closeout.
The scale and complexity differences between the processes of early-stage studies, versus those in late-stage development studies presents a greater opportunity to deliver simpler, more impactful solutions.
In our experience, the challenges above are some of the most commonly faced by organisations throughout their early clinical development journeys. When given the opportunity to address these challenges, there are five crucial steps that we advise clients to take to enable them to solve their problems and accelerate their early-stage clinical trials:
- Identify bottlenecks and streamline - refine, consolidate, and remove the activities or tools that are frequently at the root cause of delays.
- Run at risk - trigger activities earlier to shorten timelines and run in parallel to other activities while acknowledging some risk of potential rework and financial implications.
- Establish a clear decision-making framework - ensure clarity on the people or groups who are responsible for decision making and approvals and create frameworks to enable rapid decision making.
- Refine roles and responsibilities - review the people or groups who are most appropriate for owning a process or activity.
- Pilot test digital strategies and technology - implement minimum viable product solutions for automating process activities (e.g., large language models to summarise results) and improve patient experience by testing the use of digital tools and devices during the trial.
While addressing the operational challenges outlined in this blog, patient-centred design initiatives should also be acknowledged as areas that offer significant improvements to early clinical trials. Embedding digital and patient-centred design thinking from the outset can stimulate the feasibility of design options and evidence for optimising site (and patient) selection for these trials.
In addition, an important consideration is collaboration between clinical and commercial teams during early phases of development to find sustainable solutions to help realise the benefits of cost and process efficiency while maintaining regulatory compliance; as there are significantly more challenges associated with retrospective sustainability improvements. More details on the opportunities for addressing sustainability challenges can be found in Deloitte’s UK Centre for Health Solutions report on Embedding environmental sustainability into pharma’s DNA.2
Sustainable, patient-centric, acceleration initiatives that are implemented during the early stages of clinical development will enable streamlining in late-stage clinical development phases resulting in increased productivity across the entirety of the research and development lifecycle.
We would like to acknowledge Sid Prabhu for his contributions to this blog.