Making a Biomarker Strategy in Clinical Trial Operational. To Start With

Strong Arms, Strong Trials: Behind Every Breakthrough is a Biospecimen Champion

Two men in uniform sit silently as their van barrels through the misty European countryside.

Ghent. Antwerp. Essen.

The van hums with urgency, its headlights cutting through the night. Inside, nestled carefully in the van’s insulated belly, a single 10ml EDTA tube, blood sloshing gently inside. Silent. Unaware.

Its final destination: a processing lab in Berlin.

This isn’t the opening of a European noir thriller. It’s a routine delivery of a critical efficacy sample. Just a single tube. In a van. But it had to travel from London to Berlin within a 28-hour stability window.

Thanks to Brexit, pandemic-era logistics, and the organic nature of protocol development, this absurd logistical ballet became standard operating procedure.

It was ridiculous to pull off. It costed a ridiculous amount of money to pull off consistently. Not once. Not twice. But every other week. Like clockwork. 

The only thing more erratic than the logistics was the principal investigator’s blood pressure, which we monitored in real-time, metaphorically, via a barrage of urgent emails.

We got smarter. A UK-based processing lab was onboarded, trained, and qualified. Problem solved - at the cost of yet another ridiculously large pile of money.

Extreme? I wish. I hear stories like this all the time, some more dramatic, some even Oscar-worthy. And the punchline? Most of these tragicomic escapades are entirely preventable.

Let’s unravel this. (And for the impatient among us, feel free to scroll down to the epilogue. Spoiler alert: there is no van chase this time.)

The Rise of Biomarkers in Clinical Trials

In today's era of precision medicine, biomarkers have transitioned from being supplementary tools to central elements in clinical trial design. Their role in guiding patient selection, stratifying treatment groups, and predicting outcomes has fundamentally transformed how trials are conducted.

As of 2022, nearly half of oncology studies and 16.5% of all clinical trials incorporated biomarkers into their design. This trend signifies a broader movement towards personalized medicine across various therapeutic areas.

So what gives? Biomarker-guided strategies have been linked to significantly improved trial efficiency and success rates. By targeting therapies to specific patient populations, these trials tend to achieve higher response rates and generate more meaningful clinical endpoints, ultimately enhancing the likelihood of regulatory approval.

A comprehensive analysis of over 10,000 development programs showed a five-fold increase in overall drug approval likelihood when biomarkers were used to pre-select patients, compared to traditional trial designs.

Another large-scale review of 9,704 programs found a twofold increase in the approval probability for biomarker-enriched trials—15.9 % versus 7.9%.

In oncology, where precision medicine has made substantial inroads, the impact is even more pronounced. Biomarker-guided trials in breast cancer have shown a 12-fold increase in approval rates. For melanoma and non-small cell lung cancer (NSCLC), the increases are eight-fold and seven-fold, respectively. These aren't just numbers; they represent significant strides in bringing effective treatments to patients more efficiently.

The regulatory landscape also reflects this shift. The inclusion of biomarkers in marketing authorization dossiers has become increasingly common, boosting their strategic and scientific importance in drug development.

The bottom line is that the integration of biomarkers into clinical trials is not a passing trend but a fundamental shift towards more precise, efficient, and successful drug development.

The Dark Side of Biomarker-Driven Trials: Great Science Meets Grim Reality

There is no doubt that biomarkers can make clinical trials sharper, faster, smarter. But - and here’s where the plot thickens - just because a trial can be smart doesn’t mean it is. For every sleek precision trial that gets a drug approved faster, there’s another tripping over its own operational shoelaces.

Let’s take a look.

Challenge #1: The Biospecimen Bermuda Triangle

Collecting and handling biospecimens may sound simple: grab a bit of tissue or blood, ship it off, test it. Easy, right? If only. In reality, this is where many trials vanish into chaos. Delays in collection, shaky logistics, samples arriving after their stability window closes - it’s clinical comedy until it becomes tragedy.

In one NSCLC trial that required a fresh biopsy, the trial suffered a 49 % screen-failure rate and a median 34-day screening period, versus 14 days when no biopsy was needed. The culprit? Tissue acquisition and transport delays [1].

In the prostate cancer trial PROfound, among 4,047 screened men, 42 % of submitted tumor blocks could not yield an NGS result due to the age of FFPE blocks, tumor content, and low DNA yield. The outcome? One in three otherwise-eligible patients could not be molecularly stratified, prolonging screening windows and increasing costs; repeat biopsies or plasma rescue testing had to be added mid-trial [2].

Challenge #2: High Screen Failure Rates

You’d think finding eligible patients in the biomarker era would be like picking a low-hanging fruit. Turns out, it’s more like looking for an elephant’s trunk in a dark room.

Trials demanding fresh biopsies have reported screen failure rates of 70% or more, thanks to tissue inadequacy, biomarker ineligibility, or just plain logistical hiccups.

In one breast cancer study that screened 727 patients, 10% of patients were out before they were in - disqualified purely because their tissue sample wasn’t up to snuff [3]. It’s not just frustrating; it’s statistically destabilizing.

Challenge #3: Timing is Everything - and Often Missed

Timing is critical in biomarker trials. Results need to come back fast to slot patients into the right treatment arms. But long turnaround times can delay randomization windows - or worse, let the disease progress before a treatment decision is even made.

Take FOCUS4, an umbrella trial in metastatic colorectal cancer. It came dangerously close to missing its randomization window - not because of the science, but because of biospecimen issues. Of the 1,402 FFPE blocks sent to central labs, 80 had insufficient tumor, and four were lost in transit. In some cases, sites shipped only mounted slides, which compromised IHC quality [4].

The logistics delays were serious enough to threaten the critical 16-week randomization window following induction chemotherapy. And in the real world, delays like this can force investigators to start patients on treatment before biomarker results are even available, undermining the very premise of biomarker-driven stratification.

Here’s the kicker: one quality improvement initiative showed that simply optimizing the specimen workflow shaved six days off the turnaround time. Just six days. But in oncology, that’s often the gap between enrolling a patient and missing them entirely.

Challenge #4: Lost Signals and Masked Effects

It’s one thing to run into delays and screen failures. It’s another to miss the science altogether. Without using biomarkers prospectively, trials can completely overlook a real treatment effect hiding in a patient subgroup.

Exhibit A: the IMvigor010 trial. On paper? A dud. The treatment showed no survival benefit overall. But a retrospective look revealed that ctDNA-positive patients actually had a clear benefit. The problem? The trial wasn’t designed to see it. The sequel trial had to go back and do it right—with the biomarker front and center this time [5].

All these challenges don’t just make for dramatic stories - they tank timelines, inflate budgets, and jeopardize regulatory approval.

Here’s what’s at stake:

Higher Costs, Longer Timelines: Every failed screen, every retest, every lab that wasn’t onboarded in time adds dollars and weeks to your trial. And those costs escalate fast when repeated across dozens of sites.

Weakened Statistical Power: Too many screen failures? You may not hit enrollment targets, and suddenly your study isn’t powered to detect the effect you’re trying to prove.

Missed Efficacy Signals: Design your trial without biomarkers in mind, and you might overlook a therapy that works beautifully—but only in a specific subgroup.

Trial Failure: When all the above pile up, the whole program can derail. Just ask the SHIVA trial, which struggled with poor assay turnaround times and unclear biomarker yield [6].  

And regulators are catching on. They now treat biospecimen handling as a critical-to-quality (CtQ) element, not just a box-ticking lab task. Guidance documents like ICH E8(R1) and FDA's enrichment strategies push for proactive planning and risk mitigation around biospecimen operations. Organizations like ISBER and NCI have published best practices that emphasize specimen quality, logistics, and workflow integration into trial planning.

The message is clear: A strategic approach to biospecimen lifecycle isn’t optional anymore.

What’s Really Going Wrong in Clinical Trials?

Here’s the thing - most of the biomarker trial disasters aren’t caused by some unexpected twist of fate or a rogue centrifuge. More often, they’re the result of something painfully mundane: no one operationalized the biomarker strategy early enough.

Sounds abstract? It’s not.

Operationalizing biomarker selection simply means connecting the scientific brilliance (which biomarkers? why this one?) with the logistical realities (can we collect it? is the assay ready? how fast do results come back? is it even feasible across all trial sites?). It's the boring-sounding but mission-critical process of turning good science into executable plans. That’s where the strategy and tactics hit the ground.

And yet, in too many trials, this step is skipped - or tacked on as an afterthought.

Let’s be blunt: selecting a biomarker without checking if it can actually be implemented across a multi-site global trial is like designing a dream kitchen with no plumbing. Sure, the marble countertops look great, but no one’s cooking dinner.

What "Getting the Biospecimen Story Right" Actually Means

This isn’t about perfecting a single lab procedure. It’s about mapping the full biospecimen lifecycle - starting from the moment someone says, “We should use this biomarker,” and stretching all the way to data interpretation and future use.

We're talking:

-Can the right sample be collected - ethically and consistently?

-Will it survive the journey to the lab and be on time?

- Is the assay fit-for-purpose?

-Can the data feed back into the trial fast enough to influence decisions?

-And so on and so forth.

When you operationalize properly, all of this is built into the protocol from day one. When you don’t? You get the kinds of delays, failures, scientific blind, and cost overruns.

Biomarker Strategy: The First Step in the Biospecimen Lifecycle

For years, the biospecimen lifecycle has been treated like a glorified shipping schedule—beginning at sample collection and ending at lab analysis. It’s been viewed as a linear, tactical task. Box checked. Move on.

But that model no longer holds up, especially in biomarker-driven trials, where specimen planning can make or break success.

I’ve proposed a new framework that flips this thinking on its head: the biospecimen lifecycle should start with the biomarker strategy. That means building logistical feasibility, assay readiness, and clinical relevance into the trial from the very first planning conversations, not halfway through protocol finalization.

This change isn’t cosmetic. It’s structural—and it’s critical.

Who Turns Biomarker Strategy into Reality?

So, who actually makes biomarker strategy operational? Who connects the elegant science to the messy, real-world logistics of a clinical trial?

Biospecimen professionals.

They’re the ones translating aspirational trial designs into executable workflows - making sure samples are collected the right way, at the right time, processed correctly, and sent where they need to go. They’re not just box-checkers or lab liaisons. They’re the bridge between what the science needs and what the trial can realistically deliver.

Too often, this role is fragmented—spread across teams, lost in handoffs, or assigned to folks with 100 other priorities. And that’s where things go wrong.

When the biospecimen chain breaks, so does the integrity of your biomarker data.

Bottom line: if you’re serious about running a precision trial, you need someone who owns the biospecimen lifecycle from end to end.

Wrapping Up: From Blueprint to Breakthrough

We started with that mad-dash tale of a blood tube riding shotgun through Europe—and landed on a simple truth: no matter how brilliant your biomarker, it’s only as good as the plan (and people) behind it. Operationalizing your biomarker strategy from day one—framing the biospecimen lifecycle around real-world logistics and assay readiness—is what turns potential into performance.

And who makes it happen? Biospecimen professionals, the unsung architects of trial success. They’re the ones who keep samples—and timelines—on track, so your science can shine.

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If you’re ready to leave logistical headaches in the rearview mirror and truly revolutionize your biospecimen management, our team is here to help.

Let’s talk about building trials that work as smart as they look.

References:

[1]          M. L. Spiegel et al., “Non-Small Cell Lung Cancer Clinical Trials Requiring Biopsies with Biomarker-Specific Results for Enrollment Provide Unique Challenges,” Cancer, vol. 123, no. 24, pp. 4800–4807, Dec. 2017, doi: 10.1002/cncr.31056.

[2]          M. Hussain et al., “Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib),” Clin. Cancer Res., vol. 28, no. 8, pp. 1518–1530, Apr. 2022, doi: 10.1158/1078-0432.CCR-21-3940.

[3]          P. Mahajan et al., “Reasons why patients fail screening in Indian breast cancer trials,” Perspect. Clin. Res., vol. 6, no. 4, pp. 190–193, 2015, doi: 10.4103/2229-3485.167100.

[4]          S. D. Richman et al., “FOCUS4 biomarker laboratories: from the benefits to the practical and logistical issues faced during 6 years of centralised testing,” J. Clin. Pathol., vol. 76, no. 8, pp. 548–554, Aug. 2023, doi: 10.1136/jclinpath-2022-208233.

[5]          T. Powles et al., “Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma,” Eur. Urol., vol. 85, no. 2, pp. 114–122, Feb. 2024, doi: 10.1016/j.eururo.2023.06.007.

[6]          C. Le Tourneau et al., “Randomised proof-of-concept phase II trial comparing targeted therapy based on tumour molecular profiling vs conventional therapy in patients with refractory cancer: results of the feasibility part of the SHIVA trial,” Br. J. Cancer, vol. 111, no. 1, pp. 17–24, Jul. 2014, doi: 10.1038/bjc.2014.211.