In your career in the medical device industry, how many times have you been in meetings or part of discussions where post-market clinical research mandates from regulatory agencies are met with groans and frustration? Or when conducting literature searches and gathering clinical evidence, post-market studies are regarded as somehow “lesser” in credibility and value? Chances are the answers to those questions is “often” – and my follow-up question then is “why?”
There is a tendency in the medical device industry to regard clinical studies as just part of the approval process to market new products – in other words, a burdensome activity that costs a lot of time and money. We all know that clinical studies serve a valuable purpose – not least because most clinicians won’t buy products that don’t have solid evidence of safety and efficacy, and payors won’t reimburse unless the new technology can be shown to add real value. Notwithstanding these points, a sense of burden is still there, and even more so when it comes to post-market clinical research. Perhaps that is the answer to “why” – but far from being costly and burdensome, well-designed and conceived post-market clinical research can add tremendous value to the entire enterprise in a multitude of dimensions, including market penetration, product development, reimbursement, safety surveillance, indication expansion, and more.
Strategic Considerations and Planning
The key is to think about the product holistically. What does that mean? Well, if you consider clinical research as an integral part of the medical device product, rather than just an activity to be conducted for the product, you’re part of the way there. Now, if you extend that line of thinking across the product’s life-cycle, paying attention to that integral component proactively and strategically, the performance of the product, and the enterprise itself, can be significantly enhanced. In a very simple example, planning for post-market research when the product is still in preclinical studies can fundamentally change, for the better, the entire clinical/regulatory strategy. What is often the case is that a product gets through preclinical studies, discussions are held with FDA, a protocol is designed that the company feels gives them the best chance of success, the clinical trial takes place, approval is granted and then…adoption is often lower than expected (what clinicians want as evidence is not necessarily the same as what FDA wants), reimbursement issues arise (what CMS/HHS wants is very different what FDA wants), and, sometimes (increasingly), FDA is unconvinced and wants the company to conduct a post-market study under section 522 or otherwise as a condition of approval – often for which the company is ill-prepared.
Now consider an alternative approach – during the in vivo study phase, in conjunction with review of published literature and competitive analysis, product performance characteristics are identified, and a study design for human clinical trials is conceived. Therefore, the company believes it can both successfully negotiate with FDA and achieve in actual use. So far, this is identical to the traditional route. Here comes the twist though – in addition to the key elements in the pivotal study, additional elements are identified for post-market research and worked up as study synopses. These additional elements will ideally include research questions that aren’t asked in the clinical trial to provide both enhanced clinical evidence to clinicians as well as inform future product development, for example, in specific sub-populations, disease states, product sizes, positions, programmed settings, implanter characteristics (training/experience/specialty) and other human factors, etc. Similarly, although the wise manufacturer will have some element of reimbursement factored into the pivotal study, enhanced and extended cost comparison and health-outcomes work can be planned at this stage, and can be used as a discussion point with payors at the appropriate time. Discussions with FDA then need to be carefully considered from a strategic perspective. It is often advisable to go in only with the plans for performing the pivotal study. Discussing the post-market plans at this point may prompt reviewers to ask for those elements to be conducted within the pivotal study itself, which increases its complexity and expense, and potentially time to market. It’s always worthwhile to have those elements in the mental ”back-pocket” in case FDA raises them in pivotal discussions, and the process of having worked them up in the early phases is excellent preparation for such an eventuality. Then, of course, if FDA grants conditional approval on submission and evaluation of the pivotal data, the company is already well-positioned to “hit the ground running” with a program of post-market research ready to implement. Similarly, CMS/HHS may be prepared to grant reimbursement on lower levels of data if commitments are already in place to conduct broader scale post-market research to answer their cost-outcomes questions.
Tactical and Smaller Scale Strategic Considerations and Benefits
Market Penetration and Development
Physicians like to do research. Physicians like to publish. Conversely, Hospital Administrators like to save money and a leery of new technologies that may cost more. Well-designed post-market clinical research can help penetrate the market by meeting the needs of both these groups. For physicians, opportunities to be involved with, and publish on, pivotal studies are relatively few, especially if one is not an experienced and established Key Opinion Leader (KOL) – careful identification of “up and comers” and involvement of them in a post-market research program can become a very nice symbiotic relationship. In this case, for the company, they get access to eager young physicians who want to do a good job and prove themselves (who also may be much more “available” for speaking and writing opportunities than established KOLs as well), get their product used in the marketplace, get publications out there for general review, and develop long-lasting relationships with the KOLs of the future. For the physician, they get to engage in research, publish, and interact with manufacturers at levels they probably hadn’t previously. As far as the Hospital Administrator is concerned, the reimbursement for clinical research will help offset the costs of the new technology, so they’re happy – and it should not be forgotten that where contracts are in place that might preclude adoption of the product, there are almost always exceptions in place for clinical research: by the time the clinical is completed, the behaviour and use of the product has become well established. In this fashion, both market penetration, in terms of access into implanting environments, and market development, in terms of identifying and nurturing the next generation of KOLs, takes place in a fashion that benefits all parties.
Reimbursements, Outcomes & Longer-term Evidence
As previously mentioned, what is required by payors for reimbursement is quite different from what is required by FDA for approval. Far too often manufacturers will obtain FDA approval to market their devices only to find great difficulty – sometimes insurmountable without a lengthy clinical – in obtaining reimbursement. Whilst discussion on how to go about building enough metrics into the pivotal study without making it prohibitively long and expensive is beyond the scope of this blog, a successful strategy has been to engage payors in discussions regarding post-market research ahead of approval, especially when positive outcomes in terms of quality life years saved (QALYs) may take many years to accumulate; however, it would be arguably unethical to deny patients the benefits of the new technology in the interim. Companies can approach this by constructing their pivotal study in such a manner as to roll the initial subjects into an ongoing registry and follow them as patients for outcomes (which has the advantage of already having a substantial body of subject data already) or modifying the concept slightly to open the registry to additional patients to both gather a broader body of evidence as well as open the inclusion/exclusion criteria slightly (compared to the pivotal) and develop outcome evidence on real world use. Alternatively, a whole new post-market study can be constructed and deployed at new sites to aid in physician exposure to the product and gather outcome data: either methodology can, if constructed appropriately, assist in reimbursement discussions and allow for research and publication opportunities of longer term research for a larger base of physicians, thus aiding in market penetration and awareness.
A Final Comment on Legitimacy and Credibility
To some degree, although it seems to be fading (albeit slower than anyone would like), post-market clinical research has had a poor reputation with respect to its scientific legitimacy. This unhappy situation has come about through many years of practices which were, if not illegal at the time, certainly questionable. The stories of “studies” being conducted of little to no value and essentially operating as mechanisms to funnel money to physicians to buy products are legion, and in large part based in fact. Although many post-market initiatives were legitimate, and should be acknowledged as such, a sufficient number were questionable as to prompt action by industry, AdvaMed, the US Department of Justice and Office of Inspector General, and others a little over a decade ago. To cut a long story short, in order to avoid the wrath of the government, your post-market research must be legitimate and credible. It’s perfectly fine to answer important marketing questions and develop evidence for marketing claims, but one should not let marketing alone dictate one’s post-market research program or initiatives. Early identification of legitimate research questions before the product ever goes near a human is one way to ensure this – and yes, competitive claims and activity (both extant and projected) can point to legitimate areas of enquiry – as is the simple expedient of registering the study on clinicaltrials.gov and committing to publish the results, whatever is found. To be valuable, these studies and the datasets they produce should be robust, well-conducted, and capable of withstanding any reasonable scrutiny.
Comprehensive treatment of post-market clinicals is beyond the scope of this short blog article, but I hope it can be seen that when one treats clinical research, not as a task to be completed, but rather as an integral part of the product’s strategic positioning in the marketplace, the benefits that can accrue to the organization are substantial – and arguably post-market research offers the most beneficial potential of all.
If you missed the previous post in this series, Medical Device Development: Market Approval, you can view it here.
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