Our recent “Trends and Considerations in Global Infectious Disease Drug Development webcast examined how improved diagnostics may make significant differences in advancing infectious disease clinical trials.
New polymerase chain reaction (PCR)-based tests help identify pathogens rapidly, speeding diagnosis. Because treatments for antibiotic-resistant infections are a current focus of research, rapid diagnostic tests have been developed to detect MRSA-based staph DNA in as little as an hour, instead of days, providing reliable, rapid diagnosis to help with patient enrollment. PCR tests can identify tuberculosis within an hour (compared to cultures that take up to six weeks) and also detect genes for drug resistance. Similarly, S. aureus can be differentiated into drug-sensitive or drug-resistant in one hour directly from clinical samples such as wounds or mucosa.
These tests are more expensive than other methods, but they may help ensure a qualified patient population, thus enriching the study population with subjects who have the target infection. Potentially, it is possible to enroll and randomize patients known to have the target bacterial pathogen, thus considerably enriching the study population.
We polled webcast attendees to get a feel for their experience with the use of rapid diagnostic tests in a study of infectious disease treatment. The results are as follows:
- None, I have no experience with rapid diagnostic tests to date – 67 percent
- Bacterial infection/other – 15 percent
- Viral infection/respiratory – 10 percent
- Viral infection/other – 5 percent
- Bacterial infection/skin – 3 percent
Interestingly, the vast majority of our attendees have no experience to date with PCR-based tests. We expect this statistic to swing the opposite way in the near future as their importance becomes increasingly critical to patient enrollment and more tests are readily available. This lack of experience may also reflect the reluctance of trial sponsors to provide or reimburse for rapid diagnostic tests.
One of webcast presenters, industry expert Roger M. Echols, M.D., Principal Member, Infectious Disease Drug Development Consulting, LLC, has used a PCR method for skin studies to ensure patients with staph aureus infections were being enrolled. He believes the tests are a real advance. However, researchers always have to think about the gold standard and try to confirm the findings through standard microbiology.
In clinical trials, rapid tests can be invaluable to patient enrollment. However, for example, some rapid influenza tests can’t distinguish between strains A and B. Also, Clinical Laboratory Improvement Amendments (CLIA) approves some tests but not others.
As such, when it comes to using rapid diagnostic tests for infectious disease clinical trials, we provide sponsors with the following recommendations:
- Provide one test for all sites because sensitivities can vary from 50-70 percent and specificities are rarely better than 90-95 percent.
- Be sure to look at when tests are used. In our experience, we have found false positives and true negatives occur when the disease prevalence is low (at the start or end of influenza season). During the height of the influenza season, we see more false negatives and true positives.
- If you are going to make important clinical decisions with rapid tests – it is essential to conduct a full susceptibility PCR or viral culture to confirm the findings.