ARTICLE 7: Exploring the pros and cons of working with Contract Research Organisations and Functional Service Providers to deliver successful clinical investigations
In the seventh article of our series of articles on Managing Data and eClinical solutions for Medical Device Companies, the CRFWEB team discusses the different ways in whch SMEs can work with (or without) Contract Research Organisations to deliver successful, cost-effective and timely clinical investigations.
From full service to go it alone, we explore your options in depth.
We’ll explain what you need to do to ensure that your strategy choice works for you.
Article Summary
- MDR will mean more SMEs than ever before will be undertaking pre-clinical trials or post-market studies to gain or retain CE Marks
- Having a clear, detailed regulatory compliance strategy in place prior to working with CROs or FSPs is essential
- Develop detailed, granular RFPs to ensure you can properly compare competing CRO offers
- Beware cost-plus uplifts!
- Proven experience in your device sector is vital to minimize risk of delay or failure
- Always scrutinise the technology platform AND the digital roadmap, staff turnover and financial health of a prospective partner
- Give serious consideration to full data independence, even if that increases the cost of working with your chosen CRO – it may well save a lot of pain and cost in the longer run
- Full-service CROs STILL require clear oversight and transparent reporting processes
- Clarity and transparency about roles and responsibilities is vital
- Seek clear assurances about the experience of the team that is assigned to you
- FSP or CRO/FSP hybrid trial/study support models can be very successful but they come at a cost – increased overheads associated with multiple vendor recruitment exercises, more complex and demanding oversight, greater risk of confusion over roles and responsibilities
- “Go it alone” will be challenging so prepare meticulously. Have a clear regulatory strategy – and ethics body engagement plan – in place, work with KOLs on your study design. Expecting a CTMS or EDC vendor to do the heavy lifting on your behalf will not deliver
The Background – MDR will keep CRO/FSP costs high… and resources scarce
The Med Tech sector is rapidly growing and yet remains dominated by small and very small companies – c.50% of the 27000 or so companies offering products in the US and EU have less than 50 employees. The advent of Medical Device Regulation (MDR) in the EU from May 26th 2021 has meant that most medical devices are now subject to more rigorous lifetime quality and safety assessments in Europe and, in particular, far more PMCF studies than has hitherto been the case. It’s important to note, too, that any device modification will require PMCF under MDR for all Class II and Class III devices.
The upshot is that a huge number of small manufacturers will be having to undertake such activities for the first time in the coming 3 years if they wish to retain their CE Mark. Developing the resources and expertise in-house will beyond the capabilities of many such companies; it’s either uneconomic or they will simply be unable to compete against the bigger players in acquiring staff with the requisite -and increasingly scarce – skills and experience. Contract Research organisations (CROs) and Functional Service Providers (FSPs) exist to provide the skills and expertise to support trials and studies where these capabilities are unavailable in-house, but these come at a price that will be challenging for many smaller companies. So, a very large number of SMEs will be “Going it alone”, relying on professional advice, yes, but essentially taking on the trial or study sponsorship role in full as well as operational responsibility for many of the critical tasks and processes underpinning a well-designed and executed investigation. For many, though, involving CROs or FSPs – to some degree at least – will be an entirely unavoidable expense if they wish to gain or retain their CE-mark.
This article will look at ways of working with CROs and FSPs in the delivery of clinically valid trials or studies that meet the requirements of regulatory bodies – both in the pre-and-post clinical settings. Even if you are planning to “Go it alone” it’s worth your time to read through this as it will help you identify those critical tasks and processes required to ensure a successful outcome – and to recognise the common dangers facing the vendor as Sponsor.
Working with CROs and FSPs – the options
- Outsource the study in it’s entirely to a suitable CRO
- Choose a range of partners to work with whilst retaining the role of overall study Sponsor, so the so-called Functional Service Provider (FSP) model
- Work with CROs as full-service in some countries and FSPs elsewhere (hybrid model)
The facts of life
Before looking in depth at the pros and cons of a MedTech company working with CROs (and FSPs), it’s best to go back to first principles and look at some of the reasons that the costs of studies can easily spiral out of control, particularly for organisations that have little or no experience of conducting them.
The reality is that many companies often have little understanding of what they need to do by the time they engage with the regulatory process to either retain (or gain) approval. All too often the natural sanguinity of the agile go-ahead SME, combined with a lack of detailed understanding of the regulatory environment, leads to wildly optimistic planning and budgeting that unravels rapidly after engaging with the authorities. Not only is there more to do at much greater cost than anticipated, but there is also the cost of the work done to reach this point. If the company has also contracted with a CRO or a set of service providers on the basis of a false prospectus, the renegotiations are going to hurt. Naturally, there can be huge financial ramifications if the delay leads to the temporary removal of an existing CE mark (or hold-up in first-time approval).
So, it absolutely pays to invest time and resources on developing a detailed market approval strategy and, in particular, be sure you have first rate advice on the regulatory requirements for each country under consideration and a professional assessment of how the local Competent Authorities and Ethics Committees function.
If, after all the consultation and research has been taken into consideration, you’ve come up with a workable market approval strategy, it’s then paramount that you get authoritative inputs as soon as possible into the design of the trial/study protocol. Don’t stint on the desk research and, if needs be, use a specialist in the field to review studies relevant to your device. It’s important to establish an advisory board of Key Opinion Leaders and clinical trial experts in your device category to help you fine tune the detail of the protocol so that it meets the requirements the Competent Authorities and Ethics Committees you’ll be engaging with. Then, and only then, should your thoughts turn to engaging with CROs or FSPs and without question, it makes sense to research the market to find players that have proven experience in your specific device sector.
CROs and FSPs are businesses too…
An obvious point, but one that bears repetition. High-end consultancy depends on high-class expertise and experience which never comes cheaply. CROs in particular are never going to be inexpensive and to an extent, you will always be paying for their learning curve which is why aligning with a company with a proven track record in your sector is so important.
You may be offered a nice-looking cake at a reasonable price, but the cake needs icing and decorating, too. Simply, if something you need is not set out as a specific item in the quote, you WILL be paying extra for it. A senior clinical affairs executive at a larger mid-size manufacturer confided to us recently that they had received quotes from CROs to the same detailed specification that varied between $5 million and $11 million for a study in the US; so, not only is a detailed specification essential, it is also vital that responses are scrutinised to the nth degree to ensure that all items HAVE been included. Never forget, it’s you who ends up paying for errors and omissions. Make sure also that there are no innocuous looking extras such as admin costs as a fixed % of pass-through costs. Politely, this offers no incentive or reward for cost control. Caveat Emptor!
In summary: your checklist for a successful relationship…
Of course, there isn’t one! But for MedTech companies – particularly SMEs looking to work with CROs, here is a checklist that minimizes the likelihood of failure or budget meltdown:
- Take the time you need and the advice you need to develop a comprehensive market approvals strategy
- Take the time you need and the advice you need to develop a detailed trial(s) protocol
- Research the marketplace to ensure that the CROs or FSPs on your long list have proven, relevant experience
- Ensure that your RFP is as thorough and as detailed as possible, with a business model that is outcome based, NOT activity based
- Make sure that all quotations in response to your RFP include all elements of the specification
- Always take up references and always check the financial health of your prospective partner. Ask about staff turnover.
- Explore your partner’s digital maturity – poor systems and processes are likely to mean poor trials management. This is likely to be a long-term relationship and you want to work with a partner with a well-developed digital strategy at the heart of their offering.
- Develop a detailed checklist of roles and responsibilities for the Sponsor/CRO/FSP as a contractual element
- ALWAYS ensure that you have your OWN Project Manager with explicitly agreed, executive overview
So, all that having been said, let’s look in detail at the options for trial/study management open to the Med Tech SME.
Recap: what is a CRO and what exactly do they do?
CROs (Contract Research Organizations) have been an established part of the pharma/biotech sector for several decades now. One of the vital roles for CROs play when working with MedTech is the delivery of safe, ethical, accurate and properly documented clinical studies that fully comply with the regulatory and quality management requirements of the market in which the product will operate. The CRO trades on their expertise as a guarantor of the veracity, reliability and traceability of results obtained.
The term covers a diverse ecosystem of players offering differing areas of expertise; for instance, some will focus their offer on study types whilst others on specific therapeutic areas. However, most CROs will be able to offer a range of services, including:
- Project management and coordination
- Study/investigation design
- Study/investigation administration and logistics
- Regulatory engagement, interpretation, and advice
- Vendor and technical infrastructure player engagement and coordination
- Site identification, selection, activation, and ongoing management
- Support in the recruitment of patients/subjects
- Site monitoring
- Data management
- Product safety
- Statistical analysis and interpretation
- Medical/technical writing and documentation support
It’s worth noting that there are relatively few CROs currently operating with a sole focus on the needs of the medical device sector. Most CROs developed to meet the needs of pharma and biotech and therefore both the cost and expertise on offer may not easily meet either the needs or the price expectations of device manufacturers – particularly the large number of very small businesses that the sector is mostly comprised of.
MedTech and CROs working together: the options
As summarized above, sponsors can choose to outsource the entire study or investigation to a CRO (full service) or deploy several functional partners (some might be technology systems vendors or say, data analytics or regulatory experts – or even niche CROs) to focus on specific areas of activity – or phases – of the project. How the sponsor chooses to work with the lead CRO (and other functional partners) will of course be decided by a range of factors, but most obviously:
- The complexity and size of the study of investigation
- Sponsor resources and in-house expertise
- Sponsor budget
- Sponsor appetite for risk
Full-service CRO: the cons
Oversight overhead
If a company delegates the project to a full-service CRO experienced in working with MedTech, the program will most likely stay on track, but, even so, there will be no automatic guarantee that all the requisite tasks will be completed properly. It remains the sponsor’s responsibility to ensure quality, integrity, and veracity, regardless. This is why a designated in-house executive Project Manager with agreed oversight is so vital.
With a full-service CRO at the helm, the company will not be involved in the day-to-day operations of the study or investigation and so it will not be easy for them to maintain direct oversight. The larger and more complex the project, the harder this will be. Consequently, the MedTech company PM will need a working agreement with the CRO to conduct routine audits at points during the study or investigation to ensure the quality of the program and conduct a final audit as the program heads to its conclusion to ensure that it’s closed out correctly. For the smaller company, this oversight activity can itself be a significant overhead but is simply non-negotiable. Perhaps calling this a CON is an overstatement, but as it is essential, it does make sense to ask if the project is sufficiently complex that a full-service CRO really does add sufficient value to justify the cost.
At arms’s length from the action
Another concern to bear in mind for the smaller MedTech company new to the market – and for a start-up in particular – is that working with full service CROs might make it much harder for you to develop the close relationships directly with hospitals and key opinion leaders that will be vital to your long term future.
Will the “Full-service Offer” meet your expectations?
Full-service CROs will pitch for your business emphasising their expertise and deep knowledge of your therapeutic area, project type and their geographic smarts.
For the smaller company, though, there is always the danger that you have been dazzled by the promise of the glamorous “A” team but when push comes to shove, you’ll be dealing with the “B” or even “C” teams. So, if you choose a larger CRO to provide a full-service offering, you may well find that, as a relatively small piece of business from their perspective, you’ll have largely junior staff assigned to your project and, as such, their quality and experience can vary considerably. This can also impact negatively on your capability to provide adequate oversight.
The best way to navigate this gap between expectation and reality is to ensure that your CRO is well-aligned with your business with respect to mutual value. It’s got to be worth it to them to put their best people on it. However, if you are a relatively small company, you may struggle to find a value aligned CRO that has the breadth of expertise to offer the full-service you think you need.
An important word about data
What about the data? Does it make sense to let the CRO manage and control the data collected (and by extension, the EDC systems and associated Standard Operating Procedures (SOPs))? If you have opted for a full-service model, this might seem, on first sight, reasonable. Closer inspection though might suggest that this course of action could be a little short-sighted. Assuming you are in the market over the long term, and that your product portfolio continues to develop in response to new niche opportunities and evolving technology, allowing any one CRO to have your data reside on their platform could be problematic over the medium to long term with respect to data harmonization issues and analytical needs across multiple studies. The CRO you choose today may not be appropriate for the CRO you choose for another study in three years’ time, so it makes sense to plan for data independence from day one and contract directly with vendors specializing in EDC platforms, analytical and statistical analysis etc.
No strategy is cost-free of course, so if you do decide on data platform-independence, you will need to think about how you work with your CRO with respect to data collection, access, and management. There will be inevitable training and management overheads associated with this to make sure the CRO is fully up to speed with respect to the platform and SOPs and that you have a fully agreed management plan.
What’s the alternative to full-service CRO?
A widely used alternative approach is the Functional Service Provider model. You will need to bite the bullet and accept the operational oversight function for your project and work directly with a range of niche service providers rather than a single CRO, selecting on the basis of vendor expertise and excellence. When choosing a FSP partner, cultural fit, experience, flexibility, and scalability are all essential considerations. Naturally, there will be an upfront cost in ensuring that the vendors you select meet your needs and in producing shared project plans, but on the upside, you will have greater flexibility whilst maintaining overall quality if you’ve made the right decision. Additionally, detailed oversight might actually be more easily achieved working functionally rather than via the more traditional one-on-one sponsor project manager/CRO project manager match-up approach that tends to be standard practice in the full-service model.
The areas of expertise that are essential to a clinical study or investigation that are often provided by an FSP partner are:
- Regulatory consulting and engagement
- Clinical monitoring
- Data management
- Statistical analysis
- Medical writing
The sponsor is then free to focus on project management and study oversight.
For SMEs, clinical trial results can significantly impact the long-term viability of the company. Given this existential importance, contractual relationships with FSPs must be based on relevant and transparent performance metrics, the reporting of which needs to be actionable. Meticulous planning, exacting vendor selection, well-managed contractual relationships and high-quality project management and oversight will give the SME every chance of a successful and timely outcome without the need to rely on the services of a costly full-service CRO.
CRO/FSP Hybrid model
A third alternative is to opt to develop a broader overarching hybrid strategy where there is data independence and a single functional service provider for say, biometrics, BUT a range of CROs delivering either a full service or specific niche services based on a detailed assessment of critical need. One product may demand best-in-class for the product’s therapeutic area, another might require excellence for a particular study phase, and a third, experts in delivering successful studies within a specific regulatory jurisdiction. This strategy CAN offer the best of both models and has much to offer a company that has multiple products on the market BUT comes with a significant overhead in terms of ensuring effective communication between all parties.
Herding cats? The criticality of operational management and communication
Whether you chose a full-service CRO, or either the FSP or Hybrid model, success will depend on the execution of a detailed operations and communications plan. Naturally, all actors will need a thorough and detailed understanding of what they are expected to do (and indeed, the division of all tasks), but just as importantly, they will need to fully understand how, when and with whom they are expected to communicate over the lifetime of the study or trial.
Absolute clarity is required to ensure the virtual team acts as one and there are no gaps in operations due to an insufficiently detailed operational assessment and concomitant division of tasks across the team.
Howsoever you choose to work with CROs – and other functional partners – you do need to be very sure that you have the skills and expertise internally to develop and manage your chosen strategy.
Thanks, but no thanks – we ARE going alone!
So, you’ve taken everything into consideration, taken a sensible range of sound, professional advice and reflected long and hard. You’re going alone. What could possibly go wrong?
The answer is, as you will know – having done your homework – lots of things. Most importantly, as we’ve discussed earlier, the single biggest issue you may face when going alone is being too close operationally and failing to meet the exacting standards of best clinical practice and data privacy legislation. Getting this wrong could be disastrous both financially and reputationally.
However, if flying solo is the course of action that best fits your needs – and your budget – it does make sense still to ensure you are properly and independently advised on study design, regulatory requirements, and operational procedures. Fortunately, there’s a lot of resources – free and paid for – out there to call upon, so don’t cut corners – it will only cost you more in terms of time and expense if you do.
The (minimal) “Go it alone” Checklist
At the very least, you will need to take as much advice and time as you need to ensure you have in place:
- A detailed, fit-for-purpose compliance strategy
- A thorough understanding of which Competent Authorities you will need to engage with and what the critical success factors are
- A detailed trial/study protocol with relevant KOLs
- A thorough understanding of which Ethics Bodies you will need to engage with and what the critical success factors are
- A shortlist of study centres where your relationships (or those with your local representatives) are established
- A clear plan in place to ensure that you are able to fully leverage the benefits of EDC/eCOA/CTMS platforms
Our final nugget of advice is simply this; if you are going alone, don’t expect your EDC vendor to design your study or investigation – they can help you build, but that’s it. Any offer over and above should be treated with the utmost caution!
How CRFWEB can help you
Clindox are specialist providers of eClinical technology for medical device clinical investigations. We work with CROs and directly with sponsors. Our CRFWEB platform has a natural advantage over our competitors, leveraging the benefits of:
– Long established, low cost-base development and support centres of the highest calibre
– High degree of sponsor or CRO self-sufficiency for study builds (with cost-effective client onboarding processes and expert support as required)
– Solution stack delivered through a simple, flexible SaaS model
Objectively, cost-plus – the true driver obscured by the smoke and mirrors of pricing plans – favours our offer and to this end you will find our proposals will be far simpler than any of our competitors and notable by the absence of arbitrary, hard-to-justify significant variability.
All in all, we know that with our low cost-base and our ongoing commitment to self-sufficiency, simplicity and transparency, we will always provide an excellent value proposition without compromising on features or quality… whichever sector you’re from, and whatever your study or investigation needs are. Read more here
