Working with CROs
In "Patient Safety in Clinical Trials," Medelis medical advisor James T. Gourzis, M.D., Ph.D., discusses a variety of cost and patient safety issues facing the pharmaceutical industry.
If you’re outsourcing to a contract research organization, here are excerpts that focus on evaluating and working with CROs. The full interview is available for download here.
- A CRO whose monitors have deep experience in an indication, particularly oncology, are the best hedge against rising costs. Experienced, objective monitors who can properly review the files can generate higher quality data for sponsors and DMCs.
- By using independent CROs, pharmaceutical and biotech sponsors are bringing an objective third party into the study, which ideally increases visibility into problems so they can be remedied as quickly and safely as possible.
- It’s important to identify a CRO that balances quality data monitoring with speed. If speed is emphasized at the expense of quality, it can be a set up for an expensive failure.
- Whether a sponsor is using a CRO or conducting a trial with in-house CRAs, employee turnover will impact the quality of the data gathered during a trial. Studies, especially phase IIIs, tend to last for at least two years. Cleanup and site closure often takes nearly as long as the trial itself. As patients complete their study period, study monitors must record, double-check and fill in the blanks in the data-- all of which can add another year or two to the study.
- A CMO should evaluate the CRO’s site experience, relationships and selection criteria. Just as a sponsor may select a CRO based on previous experience and relationships, a CRO will use similar criteria for selecting trial sites. And appropriate site selection and management is absolutely paramount to achieving the sponsor’s goals for the trial. A CRO will have established relationships with sites and will continue to work together when the last trial has gone well. But the CRO must also step back and assess a site for each new trial. For example, at a particular time, the site staff may have changed or may be overcommitted with other trials, limiting the scope of the site’s staff activities. The CRO needs to have the relationships and controls to ensure that a sponsor’s study is conducted with experienced, appropriate sites.
- When a sponsor contracts with a CRO, it’s the CRO’s responsibility to ensure that each study site adheres to good clinical practices and safety guidances. The CRO collects the data from the sites and reports back to the sponsor. It’s also critical for the CRO to illuminate data that may be prejudicial or suspicious, protecting the sponsor from getting blindsided by problems such as false data, improper study procedures, or failure to report adverse reactions at the study site.
- While a medical officer may be tempted to shave time off site monitoring to control costs, I’d highly recommend against it. If it’s a rare disease where patient enrollment is monthly, the standard monitoring interval is typically once every four to five weeks. But if it’s a condition where enrollment is fast and furious, it may be prudent to increase that monitoring frequency in order to keep on top of the data. More frequent monitoring can get very time-intensive in oncology studies since these patients typically have voluminous medical records. Effective monitoring may require up to 16 hours per patient. A pushback on time to reduce costs may be false economy.
- A severe toxicity in phase II usually kills the compound unless it has tremendous lifesaving potential in a disease that is uniformly lethal. If the compound moves into phase III involving a larger number of patients, there is greater probability for an adverse event, especially one of low frequency. Sites and monitors have to be extremely alert for such an occurrence in a single site or the entire patient population. If a toxicity or adverse event is properly documented and analyzed, the compound may still be viable as a targeted therapeutic. The nightmare can be magnified when an event isn’t properly documented and analyzed. With poor analysis, a highly targeted therapeutic may never make it to market. Or the drug may make it to market, only to be pulled later because of major safety concerns with substantial costs to the sponsor.
We invite you to learn more about Medelis and our oncology CRO services.