Cost of Clinical Evaluations in 2023
Making sense of costs and keeping them in check
Clinical evaluations are an essential component of the EU MDR and IVDR. It can also be an invaluable source of insight when developing and marketing medical devices, in vitro diagnostics, pharmaceuticals, and other healthcare products. These evaluations involve conducting systematic research (vigilance and paid access medical literature), extensive testing (both bench testing and human studies) and analysis by subject matter experts (medical and regulatory) to determine the safety and efficacy of these products.
Not all regulatory bodies require Clinical Evaluations, such as the Food and Drug Administration (FDA) in the United States, where you claim a significate using the 510K route. This route is an instance where you can reduce the need to generate clinical data on your device by demonstrating substantial equivalence to a device in the market. The EU provides an equivalence route, but it still requires a Clinical Evaluation process (unlike the FDA submission).
You must do your clinical evaluation well. It can not only have a significant impact on the success of your EU CE marking application, but also positively impact the product post-market (marketing and market access).
This white paper aims to provide a comprehensive analysis of the regulatory costs associated with clinical evaluations. We will explore the various types of regulatory costs that companies incur during the clinical evaluation process, examine the factors that contribute to these costs, and provide recommendations for companies to manage and minimise these costs. Our goal is to help companies navigate the complex regulatory landscape while optimising their resources and improving patient outcomes.
Let’s take a deep dive into the cost of clinical evaluations in 2023, what you can expect to receive at both ends of the range, and what you should be paying for in the next sections.
What do you get for between £1,500 and £8,000?
We consider £1,500-£8,000 a lower budget range for Clinical Evaluations. It will mostly enable preparation tasks or single services that would typically have quick turnaround times. This would usually be single services such as:
Personal branded Clinical Evaluation templates.
Formulated plans, such as:
- Clinical Evaluation Plan.
- PMCF plan.
- Clinical Development Plan (with a single focus on clinical trial planning).
Formulating a Clinical Investigation Plan or elements thereof:
- Justification of a PMCF study and/or evidence.
- Formulating the clinical study methodology.
- Statistical analysis plan (calculation of sample size is included in project scope).
- CIP – Case report form.
- CIP – Patient information sheet.
- Information Brochure where section 1 of the Technical Document is already complete.
Short reports:
- Formulating a PSUR.
- Formulating the first version of an SSCP, where a compliant CER is available.
- PMCF report.
- Vigilance search report.
- Systematic literature review and report.
- Statistical Analysis Report (SAR).
Updating plans and reports:
- A well-formulated Clinical Evaluation Report, where the State-of-the-Art (SoTA) write-up is provided.
- Updating a well formulated State of the Art (SoTA).
- Updating a PMCF plan.
- Doing a simple PMCF report – user feedback survey.
Clinical Evaluation Report for a Class I where the SoTA is known:
- Class 1 (r).
- Class 1 (m).
- Class 1 (s).
Formulated templates best suit companies with an inhouse Clinical Affairs team (including medical writers). This is especially beneficial where this team has the capacity but may lack the required experience to align the correct clinical evaluation conformity route. This is also very helpful when there is a need to fast track a project for a new device.
Single task services provide quick support and help close off audit findings on Clinical Evaluations. This suits companies where the clinical or regulatory affairs teams are at capacity.
Paid templates should be:
- Personalised to your company brand format.
- Stylised to ensure consistency of formatting.
- Formatted to accessibility standards as per the regulatory and Notified Body baseline requirements.
- Grammatically correct and written to a medical writing standard but also meet a suitable readability score.
- Aligned section by section to the regulation and your product conformity strategy.
Note that alignment to the regulation is not just to quote the clinical evaluation regulatory obligations but also to outline a suitable clinical evaluation strategy (equivalence, clinical trial data, well-established technology ‘WET’) and overall conformity route. This is not only a painstaking section-by-section personalization of MEDDEV 2.7.1 rev 4, IMDRF and MDCG alignment of the template content but also personalised sections for the device and a suitable clinical regulatory route.
Outsourcing plans and reports is best for internal teams who need to free up capacity or have no ongoing access to specialist resources. It is a cost-effective way to temporarily increase capacity in your Clinical and Regulatory teams. Long-term, it saves costs on software subscriptions, literature sourcing and access to paid databases, as well as the cost and time to train and maintain the skills of staff who can use these systems.
What do you get for £15,000+?
For a products clinical evaluation budget over £15,000 – this is the starting cost for a full service Clinical Evaluation that should take 4-8 weeks to deliver. This would typically include:
Update of an MDD Clinical Evaluation to MDR producing the following documents and insights:
- First version Clinical Development Plan.
- Updated Clinical Evaluation Plan.
- Product novelty and well-established technology scientific justification.
- New Systematic Literature Reports for both target device and State of the Art (SoTA).
- Benefit-Risk justification.
- Integration of benefit-risk into Risk Management file and PSUR trending justification.
- Vigilance Search report.
- MDR compliant Clinical Evaluation Report.
- First version of Summary of Safety and Clinical Performance (SSCP).
- Well-defined safety and performance endpoint points and justification of your data sufficiency and, if gaps exist, how PMCF studies can address them.
- A PMCF study needs justification. This is a write-up when there is adequate data why PMCF study is not needed.
New device MDR Clinical Evaluation:
- See documents above.
Full Pre-market Clinical Investigation Plan pack:
- Justification of study performance and safety endpoints. This should determine effect sizes for statistical analysis.
- Formulation of the clinical study methodology.
- Statistical analysis plan including calculation of sample size.
- Case report form.
- Patient information sheet.
- Information Brochure where section 1 of the Technical Document is already complete.
- Registration of study to meet ISO 14155 and GCP.
Full PMCF study pack:
- Justification of if a PMCF study and/or evidence.
- Formulation of the clinical study methodology.
- Statistical analysis plan including calculation of sample size.
- Case report form.
- Patient information sheet.
- Registration of study to meet ISO 14155 and GCP.
Redoing a poorly conducted Clinical Evaluation:
- Redo of an SLR where a literature review was not conducted to SLR standards.
- Write a first version of a SoTA where the endpoints cannot be found, and the safety and performance ranges of the device category and alternative options were not provided.
- Address gaps where there is sufficient evidence available in the literature (but this was not used) for a device that is a well-established technology, therefore forcing the manufacturer to conduct expensive studies.
- Redo of a poorly formulated Clinical Evaluation Plan and therefore having to redo the report.
- Redo of an Clinical Evaluation which was done using an equivalence route but where the requirements for equivalence was not met (e.g., where access to the Technical Documentation of the equivalent device cannot be proven).
A full service is best suited for companies who do not have the capacity, resources, or time to conduct a full clinical evaluation. This can be a business who does have an in-house Clinical Affairs team (including medical writers). This is especially beneficial where this team has the capacity, but may lack the required experience to align the correct clinical evaluation conformity route. This is also very helpful when there is a need to fast track a project for a new device.
A company may only have capacity in their Clinical Affairs team to do CER updates, or the strategic support of the Clinical Affairs department is better strategically aligned to support innovation and/or clinical research to stay ahead of trends such as sustainability.
What are the cost risks of a poorly done Clinical Evaluation?
Money, money, money…
Clinical Evaluations are designed to find clinical data in published studies where the cost of the clinical investigation and write-up of the results was covered by someone else (your competitor, government body or academic institution). In effect, you get clinical data for a fraction of the cost. Even better, the insights give you an advantage of knowing the current safety and performance of competitors and alternative devices.
This knowledge can even help you if you still need to conduct the study as it can reduce the number of patients needed. Remember, that the cost will be per patient – so the more patients you need in your sample size, the more expensive the study will be. The more patients you need, the more time and resources it will take to conclude the study.
Going cheap on your Clinical Evaluation could be the costliest mistake in trying to obtain your CE mark if you are forced to do Clinical Investigations (see Figure I below). Your Clinical Evaluation regulatory strategy and medical writer could potentially save as much as £100,000- £1,500,000 in clinical investigation costs.
Other risks of an inadequate Clinical Evaluation include:
- Costs of failed CE marking evaluations could lead to multiple rounds in your MDR assessment. This could double your regulatory workflow and resource requirements due to redoing and resubmitting documentation, as well as lengthening audits.
- Losing time and money to redo clinical evaluations and potentially delaying your entry to market increasing your investment cost and lowering the return on investment (ROI).
- An increase in workforce capacity and reduction in your agility to get complete other workflows.
- CAPA reporting.
- Three unsuccessful conformity assessment close-out rounds with your Notified Body, would mean you have to look for a new Notified Body and restart the process.
Be aware that a low cost quote could mean the Clinical Evaluation team is not experienced or has limited qualifications to do the Clinical Evaluation. Failure to meet the required qualifications means NBs will reject your CER, no matter how well written or costly.
A suitably qualified team should conduct clinical evaluations. MEDDEV 2.7.1rev 4 states:
- The evaluators should have at least the following training and experience in the relevant field:
- A STEM degree from higher education in the respective field.
- 5 years of documented professional experience in Clinical Evaluations in MedTech.
- 10 years of documented professional experience if a degree is not a prerequisite for a given task.
- Evaluators should possess and evidence knowledge of SLR research methodology (including clinical investigation design and biostatistics).
- Evaluators should possess knowledge of research information management:
- Scientific research background or librarianship qualification.
- Experience with relevant scientific databases such as Embase and Medline.
- Evaluators should possess knowledge of regulatory requirements.
- Evidence training and experience in medical writing, systematic review, and clinical data appraisal:
- Clinical data appraisal and knowledge of validated tools (such as Cochrane, PRISMA, QUARDAS, GRADE).
- Medical writing (e.g. post-graduate experience in a relevant science or in medicine.
- With respect to the particular device under evaluation, the evaluators should in addition have knowledge of:
- The device technology and its application.
- Diagnosis and management of the conditions intended to be diagnosed or managed by the device.
- Knowledge of medical alternatives, treatment standards and technology (e.g. specialist clinical expertise in the relevant medical speciality).Be
What are the hidden benefits of a well-done Clinical Evaluation?
Clinical Evaluation, if done well, gifts you with clinical data on the State of the Art (SoTA), for your device, your competitors, and alternative treatments. It’s a differential marketing overview that gives product managers strategic insights that can make all the difference to dominate your markets.
The clinical data in literature has been published. This means manufacturers don’t need to conduct clinical trials to address the unknown safety and performance data, because it’s found in the literature. Hence, the medical writer can potentially save you between £100,000-£500,000 in clinical investigation costs and trim off months or even years in getting into the European market. We illustrate the Clinical Investigation flow below.
Having insights into device deficiencies and adverse events in your product category as well as alternative treatments can support further design improvements to improve your benefit-risk ratio. These insights are used in health economic models to calculate the actual cost (treatment of condition and adverse event health risk) versus the benefits of successful treatment. Healthcare funders such as insurance companies and government healthcare reimbursement centres use these models to justify medical treatment reimbursement. Meaning, if your device performs and is safer than your competitors, you may become the first choice device on the top of the procurement list of healthcare centres.
The Clinical Evaluation findings can also help identify key opinion leaders (KOLs) who are actively doing research on your device category. You can fast track and ensure success in further PMCF studies by knowing who is doing research and being listened to by their peers. This is also useful to plan building your safety and performance claims to capture market share.
What should you expect if you outsource your Clinical Evaluation?
Outsourcing your Clinical Evaluation means you should get the expertise and resources needed to complete it.
You should receive or benefit from:
- Clinical Evaluation Plan signed off by a suitability experienced team.
- A signed Systematic Literature Review report for each:
- State of the Art.
- Target device search.
- Equivalent device search.
- Performance endpoint and Adverse Events data on your device and the SoTA, showing the prevalence of events.
- Benefit-Risk analysis of your device against the SoTA.
- SLR write-up on State of the Art.
- Vigilance Search Database report.
- Clinical Evaluation Report signed by a suitability experienced team.
- Review and endorsement of your SoTA by a suitably qualified medical expert.
- Declarations Of Interest for each author and reviewer of your CER.
- Scientific justification of the degree of novelty of your device and if it qualifies as a well-established technology.
- Access to scientific databases (such as Embase and Open Athens) which have paywalls.
- Often the consultancies have paid access articles and can access them during the selection and data extraction phase, meaning you save on not having to pay to see if the article is suitable to use. This saves you money as only the included articles need to be sourced (£20-35 per article).
- Reference management software.
- Systematic review software.
- Data extraction and visualization software.
- Statistical analysis software and analysis by a biostatistician.
- Clinical Trial database report showing of there is current trails on the target device and your competitors.
- Documents that meet the format, layout and accessibility standards that notified bodies require.
- Documents written to both medical and technical writing standards and also meet a suitable readability score.
How can you keep costs in check?
Ensure the full scope of the clinical evaluation is clear at the initiation of the project. Any items missing from your project scope (example access and sourcing of literature) will increase the final cost. The manufacturer best does internal project management to coordinate access to the technical file, internal review and sign off the documents. It’s more efficient and cost effective for the manufacturer to appoint an internal representative to manage this.
Invest in having your Clinical Evaluation done well the first time. Clinical Evaluation under MDD was not as strict as it is under MDR. Making sure your first MDD to MDR transition CER conforms to MEDDEV 2.7.1rev4, IMDRF Clinical Evaluation outline and MDCG guidance can make considerable cost savings in the short and long term.
Avoid needing redoes of your CER as this process is costly. Invest in a compliant and comprehensive CER and SoTA. The cost of updating a good quality CER is a fraction compared to redoes, MDR submission costs and dealing with non-conformities. Above all, make sure your Clinical Evaluation Plan is valid. If it’s weak, you’ll have to redo your systematic literature review which is costly!
Manufacturers must ensure their team is skilled and resourced to conduct Systematic Literature Reviews and write a CER. Otherwise, the NB will reject your CER and it will need to be redone. Failure to meet the expertise requirement means your CER is invalid, your CE assessment will stop, and you will need to redo this.
Manufacturers may not be able to justify a full-time medical writer, medical librarian, SLR reviewer, biostatistician, clinical regulatory affairs professional, and medical expert; but MedTech Clinical Regulatory Affairs consultancies must have these expertise inhouse. Ensure that your outsourced partner has a fully equipped and qualified team where the main authors hold at least 5 years’ experience authoring Clinical Evaluations in MedTech.
The training and experience minimum requirement for Clinical Evaluators is:
- A STEM degree from higher education in the respective field.
- 5 years of documented professional experience in Clinical Evaluations in MedTech.
- 10 years of documented professional experience if a degree is not a prerequisite for a given task (MedTech regulatory inputs or information management).
There is no getting around it. Do not skimp on this step.
If you do not have data, do the prerequisite systematic literature review to define the State of the Art (SoTA). The SoTA is the most informative document in your dossier. This will inform the Clinical Development Plan, Design Master File, Marketing plan and Regulatory strategy. This avoids any redoes, major non-conformities, and delays to your MDR conformity assessment.
Ensure your outsource partner provides the SLR resources. A well-equipped Clinical Regulatory partner will have access to medical literature, databases, and ISO standards to advise if they are necessary for your project saving you time and cost in reviewing suitability of materials. As an example, during the inclusion phase of a SLR the consultancy’s literature access makes sure you do not incur the cost to procure articles (£20-45 per article) that will not be included into your data collection. Similarly with ISO standards (£800-1,750 per document) the agency validation consultant can review the suitability before you buy.
Manufacturers must also note that there are three attempts to close out all non-conformities. Beyond the third attempt the reviewing Notified Body will not support your device and you’ll need to find a new NB and restart the process.
Clearly the more project management and consulting hours you request the higher the costs of the project. We highly recommended to kick-off any of these projects with a Clinical Regulatory strategy (conformity route, clinical evaluation strategy, GPSR’s and classification)is provided and clarified with your internal team. This avoids repeated questions throughout the project ensures interdepartmental alignment and focussed energy on finalising documents.
Clin-r+ recommendations
Invest in your Clinical Evaluation! They pay for themselves in informing the design, regulatory and marketing lifecycle management of the device. This is the source for the majority of non-conformities and the main reason why MDR conformity assessments get delayed or prove unsuccessful. If done poorly, they are costly and a source of frustration that can demotivate your team. On the flip side, a compliant and comprehensive CER informs, creates confidence, and can inspire innovation. It’s the document that can make or break both your MDR conformity assessment and your budget.
Clin-r+ Ltd can assist medical device manufacturers with gap assessments, clinical evaluations, the transition from MDD to MDR and the demonstration of equivalence in compliance with the requirements of the MDR 2017/745. Get in touch!
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