Fix, replace or augment: Key considerations for rescue or transition studies in medical device clinical trials.

Clinical trials are demanding, rigorous and time-sensitive. This is especially true for medical device development where the protocols, patient selection or surgical interventions may be highly specific. The demands on all parties – developer, Contract Research Organization (CRO), principal investigator, site staff and participants – are high, so it is little wonder that when a program is not meeting timelines, thoughts of “rescue” or “transition” may need to be considered.

If a CRO is being used to execute the study, replacing an incumbent CRO with another is often an option of last resort for developers. This is due to the time, effort and reputations invested in selecting, commissioning and setting-up a CRO to conduct the program or study. Any decision taken around transitioning existing studies should, therefore, be done with caution and pragmatism.

Unquestionably, everyone involved in the execution of a study will be focused on delivering quality outputs and efficient timelines, so that pragmatism is often found in seeking to augment existing relationships with additional third parties contributing to an existing program in order to keep it on track.

There are numerous reasons why even well-qualified, specifically selected CROs sometimes struggle to deliver studies in-line with expectations. The complexity of a clinical trial may lead to unexpected pitfalls for CROs who lack specific therapy area or specialized patient setting experience (e.g. neonatal intensive care or post-op), or struggle to recruit the right, diverse or enough patients into clinical trials. Sites, too, invest considerable time, resources and credibility to get to the “green light” ready to enroll participants.  Being able to support their success in recruiting is as important to them as other stakeholders in the trial. Slow start-up, lack of resources, difficult or hard to recruit patient populations and escalating costs associated with timeline extensions can all knock a trial off plan, and force the need for “rescue” or “transition” to enter the lexicon.

The specialist nature of Medical Device focused CROs

Biopharmaceutical developers have a wide choice of CROs with a wide range of capabilities: global, regional, niche and/or therapy-area focused. Less so for Medical Devices. The due diligence of vendor selection will seek to balance qualifications, experience, past performance, geographic coverage, timelines and services provided. Yet while the core requirements are similar, the realities of running studies for Medical Devices may not be apparent.

Medical Device development programs benefit from:

• Dedicated medical device teams with experience in delivering trials both globally and across a wide range of therapeutic areas
• Genuine efficiencies gained through an integrated end-to-end service delivery approach, capturing and utilizing insights from surgical, interventional and safety/biocompatibility testing through to protocol and trial design and ultimately clinical study execution
• Decentralized or partially-decentralized trials where technology can be used to gain additional data points, offset the need for in-person visits, improve patient retention and where proven investigators can be used as the Principal Investigator (PI), with local PI’s acting as sub-PI’s as needed, based on local regulation. This is particularly important as patient recruitment for clinical trials becomes more specialized and access to PI sites for check ins, screenings, or sample collection may not be feasible (e.g. COVID restrictions or ability of diverse patients to access sites). This is especially true of medical device trials that typically have fewer sites (compared to biopharmaceutical trials) and many more trials being run in community settings.
• Working with a CRO that is already ISO13485 certified. These important global standard outlines requirements for quality management systems of companies involved in the medical device industry.  Numerous countries require manufacturers to obtain ISO 13485 certification in order to market their medical devices.  The device manufacturer is responsible for ensuring that outsourced activities comply with the ISO standard, so any clinical development work that is undertaken with a partner who does not operate under this standard will necessitate additional oversight from the manufacturer. 

Rescuing studies and rescuing relationships: Partnerships vs. transactions

Clinical trials are challenging, and many of these challenges cannot be entirely predicted or anticipated at the outset of a trial. This simple fact establishes four important parameters for selecting a CRO.

1. Experience: selecting a CRO with therapeutic area and medical device specific experience helps because this expertise can help guide the team to anticipate – and mitigate – risk for the program from the outset.  The right CRO for your study also understands the patient population and demands associated with your protocol. The CRO should also be able to tap into Key Opinion Leaders (KOLs) who have experience in the space and can bring their particular insights and protocol considerations from the beginning. Experience also brings an understanding of how studies should be performing, to evaluate performance on an on-going basis, or suggest changes to the protocol, additional training and risk mitigation while the study is in flight.
2. Core capabilities: Patient recruitment and site activation will likely remain the most unpredictable variable in any clinical trial, so a CRO with access to data-enabled and targeted recruitment tools as well as access to diverse patients and proven investigators is key.
3. Scale and Flexibility: Sometimes, simply applying more resources to a study is what’s needed to get it back on track. A CRO with a flexible attitude and the ability to scale to respond to your changing study needs or timelines, can help to keep programs on track.
4. Partnership: Partners are invested for the long term, and typically integrate active senior level oversight on programs because there is a genuine desire to see that partnership mature. The right partner together with the right processes, can proactively work with you to recognize, discuss and mitigate emerging challenges. Ultimately, relationships with CROs and other contributors are either driven by transactions or by a partnership approach. Transactional relationships are more likely to result in relationship challenges as they are based around a set of pre-agreed parameters. Actively seeking true partners, that are invested in your success is “cheap insurance” for when clinical study challenges emerge, and can result in a mutual verification of program parameters, open dialogue about possible concerns and an active program of risk mitigation. Indeed, the maturity of a partnership approach will include the pragmatism to know when rescue studies should be considered to augment established programs.

When to use the “nuclear” option of trial transition

Ultimately, the decision to transition a trial to another CRO reflects a break down in relationship to the point at which confidence is lost. Given the consequences and the threat of yet more delays on a program, critical objective assessment of the existing relationship needs to be carefully thought through, focused on 5 key areas:

1. Regulatory concerns including global sensitivities
2. Study conduct concerns including adequacy of approaches to patient recruitment
3. Data integrity/quality and Trial Master File concerns
4. Team dynamics including experience
5. Communication issues

Any one of these could be a deal breaker for an existing relationship, but it is also possible to use this list as a guide to make a decision to augment an existing relationship (with, say, additional regulatory support) or whether a complete reset is appropriate.

When the decision is made to transition your trial to a new CRO, careful consideration should be given to ensure that you understand the following: timing of transition and the potential for increased delays, data transfer and access, funding and investor relations, contract negotiations and regulatory scrutiny.

How to transition a trial, or components of a trial

Of course, if KPIs have been established early and regularly monitored, and relationships carefully maintained by all parties, it will be obvious when a new approach is needed. But if “rescue or transition” is needed,

• Determine if individual components can be outsourced and added to an existing program, or whether wholesale change is needed
• Seek out a provider experienced in conducting transition/rescue studies, and who is able to bring integrated resources forward quickly under the oversight of a senior individual. Revisit other contenders evaluated during the original bidding process.

About Labcorp Medical Device and Diagnostic Development

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