Smart People Can Still Design the Wrong Study

I was in an investigator meeting recently where the conversation shifted in real time.

The clinical investigators came in with exactly the kind of perspective you would expect from smart, experienced physicians:

• What could be measured?
• What would patients tolerate?
• What would make sense in practice?

All important questions.

But once we walked through the reimbursement, market access, and commercialization requirements sitting behind the study, the frame changed. The group could see why the original protocol, while clinically reasonable, was not the study the company actually needed.

That was not because the investigators were wrong.

It was because they were looking at the study through the lens they are trained to use: clinical relevance, feasibility, patient care, and scientific credibility. Medtech companies need all of that. But they also need the protocol to answer the questions that determine whether the technology can move from promising to reimbursed, adopted, and used.

That is where medtech evidence plans start to drift.

Clinical Input Is Essential. It Is Just Not the Whole Evidence Strategy.
I have enormous respect for clinical investigators. Good investigators make studies better. They understand patients, workflows, disease progression, clinical burden, measurement realities, and what is likely to happen at the site level once the protocol leaves the slide deck and enters real life.

Their input is not optional. It is essential.

But most clinical investigators are not in the business of understanding market access requirements for medtech companies. They are not usually responsible for payer evidence, coverage strategy, value analysis committee review, CPT coding progression, pricing justification, investor milestones, or commercial adoption.

So when they are asked to help design a protocol, they often design the study they know how to design.

That study may be scientifically reasonable. It may be publishable. It may even be clinically important and robust.

But it may not answer the question the company actually needs answered.

For medtech companies, that distinction matters. A study can look rigorous, cost a fortune, and still fail commercially if it does not generate evidence needed for reimbursement, adoption, and utilization.

The Protocol Is Where Commercialization Strategy Becomes Real
A protocol is not just a research document.

For a medtech company, the protocol is where the reimbursement strategy, market access strategy, clinical strategy, and adoption strategy either come together, or quietly drift apart.

I tell my kids all the time: being smart is not the same thing as being pointed in the right direction. You can work incredibly hard, do everything with good intentions, and still end up somewhere you did not mean to go if you started with the wrong map.

Evidence generation is like that. A protocol can be thoughtful, detailed, and scientifically defensible, and still not be pointed at the decision the company actually needs to change.

A team starts with a clinically sensible question. The investigators weigh in. The endpoints seem reasonable. The study population is defined. The assessments are selected. The site plan comes together. Everyone feels like progress is being made.

Then someone asks: Will this endpoint matter to payers? Will this comparator reflect real-world decision-making? Will this design help a value analysis committee understand the operational or economic impact? Will the study capture healthcare utilization, treatment burden, adherence, or workflow changes? Will the evidence help the company move toward reimbursement, coverage, adoption, or broader commercialization?

If those questions are asked too late, the protocol may already be pointed in the wrong direction.

Pragmatic Real-World Study Design Is Different
Pragmatic real-world study design is not a shortcut around rigor. Done well, it makes rigor relevant.

Traditional clinical trials are often designed to answer whether an intervention can work under controlled conditions. Pragmatic and real-world studies are usually designed to understand how a technology performs in settings that look more like actual care delivery. The NIH Pragmatic Trials Collaboratory describes pragmatic clinical trials as studies that take place at the site of care and generate real-world evidence on the benefits and risks of treatment options for providers and patients.

That difference matters for medical devices because adoption does not happen in a vacuum. Devices have to fit into clinical workflows, patient routines, facility operations, training models, reimbursement pathways, and provider behavior.

In the study that prompted this post, the design evolved into a mixed facility and in-home, multi-site pragmatic real-world study. It included multiple data sources, daily patient diary information, standardized patient-reported outcome measures, and physical or functional assessments. There were also practical considerations around site execution, patient burden, adherence, training, and how outcomes would be interpreted by different stakeholders.

Those details matter.

Pragmatic study design requires intentional choices:

• Which patients reflect the population that will actually use the technology?
• Which settings reflect real-world care?
• Which endpoints are clinically meaningful and commercially useful?
• Which data sources are feasible, credible, and fit for purpose?
• What evidence will help the company advance the next decision?

Where Protocols Often Miss the Market Access Lens
Most medtech protocols do not fail because people are careless. They fail because smart people optimize for the wrong decision.

Baseball has taught me that the right play depends on the situation. You do not coach a hitter the same way with two outs, a runner on third, and the tying run at the plate as you do in a batting cage on a Tuesday night. The mechanics still matter, but the situation changes the decision.

Protocol design works the same way. The clinical mechanics matter: endpoints, inclusion criteria, assessments, data collection, site workflow. But the commercialization situation matters too. A company preparing for payer discussions, value analysis review, or a reimbursement milestone may need a different study than one designed primarily for clinical validation or publication.

A clinician may optimize for clinical meaningfulness. A site may optimize for feasibility. A medical affairs team may optimize for publication. A commercial team may optimize for speed. A traditional CRO may optimize for execution.

All of these perspectives are legitimate. The problem is what happens when no one is responsible for integrating them.

KOL Input Should Be Integrated, Not Replaced
The answer is not to minimize investigator input. That would be a mistake.

The answer is to put investigator input into the right evidence-generation framework.

Clinical investigators can tell you whether an endpoint is meaningful, whether a patient diary is realistic, whether an assessment is too burdensome, and whether a site can actually execute the protocol as written. That input matters.

But a commercialization-focused protocol review asks additional questions:

• Will this study help address payer skepticism?
• Does the endpoint strategy support reimbursement discussions?
• Does the comparator strategy reflect the real decision being made in the market?
• Are we measuring outcomes that matter to value analysis committees?
• Does the study capture patient burden, provider burden, or resource utilization where relevant?
• Will the evidence help support market access, adoption, or coverage?
• Are we building a study that can be executed without collapsing under its own complexity?

The best studies integrate clinical credibility and commercialization relevance.

Signs Your Protocol May Need a Strategic Review
A protocol review is not just a grammar check. It is not simply a review of inclusion criteria, visit schedules, or data collection forms.

A strong protocol review pressure-tests whether the study is designed around the decision it needs to change.

Here are some signs your protocol may need that kind of review:

• The protocol was designed primarily around KOL input or one site’s workflow.
• The endpoints are clinically reasonable but not clearly tied to reimbursement or adoption.
• The comparator reflects academic preference more than real-world standard of care.
• Patient burden, treatment burden, workflow, adherence, or utilization are not being measured.
• The study could generate a publication but may not answer payer or value analysis questions.
• The team cannot clearly explain which commercialization milestone the study is meant to support.
• The protocol looks rigorous, but no one has pressure-tested whether it advances market access.

The wrong study rarely looks obviously wrong at the beginning. Usually, it looks thoughtful, defensible, and created by smart people. The problem shows up later, when the data are in and the company realizes the study did not answer the questions that mattered most.

What a Strategic CRO Brings to Protocol Review
A strategic CRO is not there just to run the study.

It is there to help make sure the study is the right study before the company spends the money.

Traditional CRO execution matters. Sites need to be activated. IRB submissions need to move. Data need to be collected cleanly. Monitoring, statistics, data management, and reporting all matter.

But for medtech companies, execution alone is not enough.

If the protocol is not aligned with reimbursement, market access, adoption, and evidence-generation strategy, excellent execution may simply deliver the wrong answer efficiently.

A strategic CRO brings the clinical, operational, reimbursement, and commercialization lenses together early enough to make a difference. The goal is not to make the study bigger. Sometimes the best protocol review makes the study more focused.

The right study is not always the largest study, the longest study, or the most academically elegant study. It is the study that answers the stakeholder decision.

Why This Matters Now
Medtech companies are under pressure to move quickly. Many are trying to preserve runway, satisfy investors, support reimbursement milestones, expand coverage, or show that a technology can scale beyond a handful of enthusiastic clinical sites.

That pressure can lead teams to move too quickly into study execution.

But speed only helps if the study is pointed in the right direction.

A protocol that is missing payer-relevant endpoints, the wrong comparator, or real-world implementation measures can create expensive rework later. It can delay reimbursement. It can weaken value communication. It can make a promising technology harder to adopt.

And sometimes, it forces the company to go back and do the study it should have done the first time.

That is painful. It is expensive. And in many cases, it is avoidable.

TTi’s Perspective
At TTi, we do not see investigator input and market access strategy as competing priorities.

The best protocols integrate both.

Clinical investigators help make the study credible, feasible, and meaningful in practice. A strategic CRO helps make sure those clinical decisions also support reimbursement, adoption, market access, and commercialization goals.

Because nothing happens in a vacuum. The endpoint affects the reimbursement story. The comparator affects payer confidence. The data source affects credibility. The site model affects feasibility. The patient burden affects adherence. The analysis plan affects whether the results can be used.

Before you launch a pragmatic, post-market, or real-world study, it is worth asking a blunt question:

What might we be missing?

Not because the team has done anything wrong.

Because every stakeholder sees the study through a different lens. The protocol review is where those lenses need to come together.

Remember:

Evidence is only valuable if it changes the next decision.

– Dr. April