Short-Term Research, Long-Term Ignorance

I am a member of the taskforce that is developing implementation plans for the National Pain Strategy. The optimal use of opioid medication is one of the many issues the taskforce is charged to address. Speaking in no way offically for the task force, my efforts to educate myself further in this area has led me to a jaundiced personal observation about how medications are researched.

The critical questions regarding opioids are whether they relieve acute pain, whether they relieve long-term pain, and whether they have long-term negative effects (e.g., addiction, hormonal disruption, hyperalgesia). To engage these questions, I recently read two widely-cited reviews of the literature, one by Jane Ballantyne and Naomi Shin and the other by Andrea Furlan and colleagues.

Both are thoughtful, well-written reviews that demonstrate that rigorous clinical trials are common in this area. However, the evidence base is almost useless for answering questions about the long-term costs and benefits of opioid medications. In the 41 randomized clinical trials that Furlan et al. review, the impact of the medication was evaluated for an average of only 5 weeks. That’s enough to show acute pain relief effects, but leaves us in the dark about what happens to the millions of people who take these medications over longer periods.

None of this is unique to the study of pain medication. Anti-depressants, which are prescribed long-term to tens of millions of people, are typically evaluated in 12 week trials. I suspect experts in cardiology, rheumatology and endocrinology could provide examples in their own areas of medications that are widely prescribed for the long term but only evaluated in the short term.

The primary reason for the short-termism of pharmaceutical research is that much of it is funded by the industry itself. Short-term studies are cheaper and meet the FDA requirements for demonstrating efficacy. If there are long-term problems with a medication a company is developing, it would be economically foolish of them to design a study that would reveal them.

The public of course has a different balance of interests and cares what happens to its health beyond a 5 or 12 week window. But public research money to pursue those interests scientifically is drying up, meaning that we will continue to learn about the long-term effects of many medications only by nervously watching what happens when millions of people take them in the course of receiving health care. That’s no way to protect the public health.