A 2018 study out of MIT Sloan School of Management showed only 13.8% of drug development programs lead to FDA approval. That’s an improvement from previous estimates, which hovered at around 10%, but still an alarmingly high failure rate. In today’s competitive market, reducing failure rate is one sure way to maintain R&D returns.
While issues around safety and efficacy cause most clinical trial failures, lack of funding, poor study design, challenges around inclusion and exclusion criteria, low patient recruitment and retention, and simple mismanagement can all send a trial down the tubes.
Don’t assume your clinical trial will survive endless change orders, extended deadlines, cost overruns, and missed objectives. Recognizing early warning signs that your trial is in trouble, and taking quick decisive action, can often get studies back on track. Improving operations can solve most failure risk factors, thus increasing the odds of success.
4 warning signs your trial needs rescue
Clinical trials fail for both clinical and operational reasons. Here are a few operational reasons to call for a life preserver.
• Over budget. A study published in JAMA showed 22% of phase 3 studies examined failed due to lack of funding.1 A separate study estimated the median cost to develop a cancer drug at $648 million. The median revenue after approval was about $1.6 billion. The median revenue of a failed drug development program…$0.
• Missed deadlines. Missing important study milestones drives up costs and jeopardizes quality and study funding. Missed patient recruitment deadlines, databases not locked on time, and excessive delays in regulatory approvals all point to trouble ahead.
Even minor deadlines can build up and derail a project. If your current CRO fails to deliver documents when promised or regularly postpones training and meetings, it could lead to missed major deadlines and a derailed project.
• Recruitment challenges. Delayed enrollment, or not enough enrollment, will stop a trial in its tracks. Low patient recruitment could stem from overestimated enrollment rates, poor site management, unaddressed patient concerns, or lack of enthusiasm from the investigator. A study out of the UK found that out of 114 trials evaluated, less than one third recruited their original target and about one third required extensions.2
• Logistical issues. A motivated team will go a long way toward keeping your trial on track. A disorganized, inexperienced team increases the risk of a disorganized, mismanaged trial.
The project manager can also throw a trial into disarray. An inexperienced project manager may not have a clear idea of how to set accurate timelines, budgets and enrollment data, much less develop a highly detailed work plan.
Pay attention to unreturned phone calls, unanswered questions and missed major and minor deadlines. An experienced project manager with relevant scientific and regulatory knowledge will keep a project on track and on budget, saving the sponsor considerable time and money.
Your study is falling apart. Now what?
If your clinical trial suffers from one or more “rescue” warning signs, don’t wait to send an S.O.S. call. Early intervention is key to save faltering and failing trials.
Biorasi follows a concept called “Return on Intervention.” Early in a trial, intervention provides dramatic benefits for minimal cost. An assessment or trial review may be all that’s needed to steer a project back on track. As a trial progresses, the cost for intervention increases because it requires more involved efforts, such as modifying trial protocols or adding additional sites. If you need an intervention, don’t delay in contacting an expert.
Behind most warning signs lies a deeper, fundamental cause. A few missed deadlines may signify an underperforming project manager or a flaw in study design. Delays in site activation may stem from that site’s inexperience or an ineffective CRO. Aim to resolve the underlying cause to reduce the odds of more red flags in the future.
When fixing problems with your study, sometimes it’s not feasible to resolve the underlying issue. For example, when enrollment lags due to a complex protocol or highly specific inclusion criteria, it may make more financial sense to add sites rather than amend the protocol or inclusion/exclusion criteria.
In other cases, you may need to re-evaluate the project plan, consolidate vendors, or make other fundamental changes. Review your protocol and study documents to determine the most effective (and cost-effective) way forward.
When you can’t save it alone
If your clinical trial continues to falter even after your best efforts to save it, consider hiring a second (or third) set of eyes. Pharmaceutical companies routinely contract with second CROs. That outside party may perform an assessment, perform additional data cleaning, or initiate new sites.
A second CRO can also oversee larger portions of a trial, such as data management or, for large studies, full-service functions for a specific geographical region. In some cases, the trial sponsor may replace the original CRO with the second CRO.
To learn more about how to spot and mitigate planning problems, enrollment issues, and other failure points, download our webinar: “Solving At-Risk Trials: Identification and Mitigation Strategies for Clinical Trial Success.”
During the one-hour webinar, you’ll find out how to recognize underperforming trials and develop early intervention tactics to up your odds of success. Download the webinar today.
Kurt Gehlsen, PhD
VP, Chief Scientific Officer, Biorasi
Wayne Bowden, MBA
VP, Program Development, Biorasi
1. Hwang T.J., Carpenter D., Lauffenburger J.C., Wang B., Franklin J.M., Kesselheim A.S. Failure of investigational drugs in late-stage clinical development and publication of trial results. JAMA Intern. Med. 2016;176:1826–1833.
2. Campbell M.K., Snowdon C., Francis D., Elbourne D., McDonald A.M., Knight R., Grant A. Recruitment to randomised trials: strategies for trial enrollment and participation study: the STEPS study. Health Technol. Assess. 2007;11:105. iii-ix.