CROs can range from large, international full-service organisations through to small, niche speciality groups. One of the key advantages for a pharmaceutical firm using a contract research organisation (CRO) is that it can mean being able to take a drug from conception through to Food and Drug Administration (FDA) or, in Europe, European Medicines Agency marketing approval without having to maintain expensive in-house research staff.
Yet, as Lisa C Feeney, vice-president, clinical operations at clinical outsourcing firm ExecuPharm, cautions, the danger for a pharmaceutical firm is assuming that using a CRO can simply push the process ‘off desk’.
"CROs have something of a reputation for putting in lower-level resources on trials because they can be seen as something of a money-maker, and, if you have lower-level people, that can give you a higher margin. But you need to make sure that the people assigned to your project are suitably qualified, that they have experience in the specialist therapeutic areas and the indicators that you need," she points out.
"It is not a question of outsourcing and then not having to think about it, not at all. There will be quite a significant amount of overseeing if it is being done correctly. You cannot just say ‘come back when you have finished and when you have a data-set for me’," agrees Lauri Sirabella, senior vice-president, clinical operations and strategic business development at ExecuPharm.
The fact the buck – whether a 483 FDA warning letter or highlighting of corrective action/preventive action (CAPA) deficiencies or other serious sanction – will always stop at the pharmaceutical firm is another imperative for getting this question of oversight right, agrees Feeney.
"At the end of the day, it is your study and your data, and anything that goes awry, who is it really going to hurt? The pharmaceutical company. Moreover, if you file a new drug application, it is almost guaranteed that you will be inspected," she says.
"Vendor oversight plays a hugely important part in this, and it is imperative to have a vendor oversight plan in place.
"This needs to specify and outline clearly the expectations on all sides. After all, at the end of the day, while a pharmaceutical company may outsource to a CRO vendor, the sponsor organisation is still the one that carries the ultimate responsibility," she adds.
So how can you stay on top of the CRO relationship, and what strategies should you employ to get the best out of that relationship, for both sides?
Feeney argues that oversight and management have to be on the agenda right from the beginning, during the CRO selection process.
"For example, there has to be a willingness from the very beginning to share past audit information, findings inspection and regulatory information, what CAPAs have they put in place and so on. What are their past performance indicators like and what, too, about their future performance indicators? Selection is a very important part of this whole process," she advises.
"There will inevitably be a cultural element to it, a feeling in your gut that this is going to be a good relationship. However, when talking with a CRO, you do need to ensure you are getting beyond the business development people.
"You need to be asking key questions such as who the project manager is, what their experience and capability are, how the service is going to be managed, how any problems and issues are handled, and so forth.
You need to be sure the people doing the job are properly trained and qualified, so it is imperative to look at their trial and training record, their résumé, background, functional capacity – the contract should include a minimum level of experience that people are expected to have.
"Also the questions you need to ask when you select a vendor are quite different to those you need to ask on an ongoing basis once the contract has been signed," Feeney continues.
Putting in place a vendor oversight plan, as highlighted by Feeney, is in this context definitely a must.
"Another good idea is to put together a detailed task ownership matrix (TOM) outlining who is going to do what. Some large pharmaceutical firms have had these in place for years, but it is surprising how many smaller firms, and even some mid-sized firms, do not do vendor oversight particularly well," advises Sirabella.
Another important element to have in place is a clearly communicated and well understood escalation plan, says Feeney.
"So, when the CRO encounters scenario A, B, C or D it knows what needs to be escalated back to you and in what sort of time frame; for example, within 24 hours. So it might be around significant trends or medical findings, or lab data trends or a safety concern.
"You should be very clear on what you expect from the escalation process. If you are mid-trial, for example, and suddenly find there is a massive safety concern, you need to be sure your CRO clearly understands what is expected, especially if that means having to stop patients having the drug immediately," she emphasises.
