In the strictly regulated business of developing new medicines, medical procedures and devices, when it comes to the management of third-party vendors, the question of where the buck stops has never been so complicated.
Ultimately, the pharmaceutical company sponsoring the research must take full responsibility for all their trials, but many sponsors are now outsourcing the monitoring of the clinical trial to specialised contract research organisations (CROs), and then in turn outsourcing certain parts of the work to third-party vendors or sub-contractors. This makes the question of who is responsible for ensuring that Good Clinical Practices (GCP) are adhered to a hotly-debated issue.
GCP regulations ensure both the protection of patients and credibility of data, so oversight must be maintained to protect the sponsor’s interests and ensure the delivery of a successful clinical trial – on time and on budget.
2013 guidance from the U.S. Food and Drug Administration (FDA) on oversight in clinical trials states that although CROs must comply with any monitoring responsibility delegated to it by the sponsor, the sponsor still retains ultimate responsibility for oversight of the work done by the CRO. The FDA recommends that the sponsor should carry out periodic reviews of monitoring reports and performance or quality metrics, and both parties are instructed to implement processes to exchange the information required.
In order to accomplish this, relationship and trust building as well as a clear agreement about oversight responsibilities is of paramount importance.
The oversight dilemma
Sponsors still struggle to find a balance between the risks and benefits of transferring the oversight of third-party vendors to CROs – and some may be of the opinion that the paperwork, time and resources required may not be worth the apparent benefits.
The root cause of the rumblings of discontent on the part of sponsors may simply be attributable to growing pains as all the stakeholders settle into a changing market, trying to find the most efficient and painless operational models in a tightly regulated industry.
However, the financial burden on the sponsor is prohibitive; in addition to paying a CRO to manage certain aspects of a clinical trial, the sponsor faces severe financial, operational and reputational setbacks and if mistakes are made in terms of compliance.
The sponsor must also allocate its own human resources to oversee both the CRO and the third-party vendor, leading to possible duplication of work, bureaucracy and delays.
For the sponsor, one of the prevailing concerns is that costs might be less transparent when CROs manage third parties as well as that the CRO may not fight for the best interests of the sponsor when negotiations are entirely left in their hands.
The importance of clear metrics
From the very beginning of the award, sponsors and CROs need to put painstakingly clear agreements in place to define how monitoring will be measured and by whom. Although Risk-Basked Monitoring (RBM) has already introduced a structured approach to the assessment of risks for clinical trials, the industry still has to develop a standardised way of benchmarking CRO and vendor performance.
This means sponsors currently have a hit-and-miss approach to developing yardsticks to hold up to their CROs and sub-contractors – so which metrics seem to be the most effective thus far?
The metrics of monitoring a vendor will not be the same as the metrics by which the progress of a clinical trial is measured, which includes things like patient recruitment, study setup times, data discrepancies and adverse events.
The metrics needed to keep an accurate overview of a vendor’s performance from study startup to close-out would include factors such as monitoring visit frequency, study conduct (for example, site relationships, consent form quality), treatment and compliance, clinical research associate (CRA) turnover, safety reporting (adverse and serious adverse events) and data discrepancy resolution rates.
More innovative metrics such as an assessment of the CRO/vendor’s performance from the study site’s point of view is possibly another valuable measurement.
Budget and contract control can also be monitored by keeping track of any discrepancies or variances in the budget as well as monitoring change orders and scope creep.
When things go off-course, the sponsor will first of all need to be monitoring the risk to know that it exists and once one has been identified, corrective measures must be put in place to ensure that the study gets back on track without being completely jeopardised.
2. Re-train if necessary in order to clarify the sponsor’s expectations.
3. Agree on a course of remedial action and document exactly what needs to be done according to a timeline.
4. If the issue persists, it may be worth bringing in highly experienced consultants to supervise the CRO and
manage their performance.
5. If all else fails, initiate procedures to terminate the CRO’s contract and find a replacement. This may be costly
and time-consuming, so this should always be the last resort.
An industry-wide survey performed by R.H. Bouchard and Associates in 2013 showed that where sponsors did not allow CROs to have oversight responsibilities over third-party vendors, 46 percent felt more confident managing third-party vendors by themselves, 42 percent felt that CROs were not looking out for the sponsors’ interests during negotiations and 24 percent were of the opinion that CROs did not do a good job of managing third-party vendors.
Third-party vendors also prefer to deal directly with sponsors in many cases, believing they can understand the sponsor’s expectations better, thereby perhaps opening the door for a more strategic long-term relationship with the sponsor.
Given that many sponsors would like to delegate more of the oversight role to CROs, it may be beneficial to use a step-by-step approach towards empowering CROs while at the same time solidifying the relationship between the two parties.
If much of the oversight burden can be shifted away from internal resources the sponsor would still need the CRO to be transparent on costs, selection, pricing and compliance.
There may not be any one-size-fits-all answer when it comes to the management of third-party vendors, but communication and transparency are the key to ultimately making these relationships work.
An entire stream was dedicated to Governance and Oversight at Partnerships in Clinical Trials Europe 2016. Over 1000 industry professionals gathered in Vienna - find out more at lifesciences.knect365.com/pct-europe.