CDC Manipulated Data to Deceive

Durations of Opioid, Nonopioid Drug, and Behavioral Clinical Trials for Chronic Pain: Adequate or Inadequate?

This commentary presents the case that the CDC manipulated the data it used as a basis for its opioid prescribing guidelines.

By imposing an arbitrary non-standard constraint and excluding some studies that were included in earlier reports, the CDC created a different interpretation by using a different set of data.

Objectives. A recent US federal review and clinical guideline on opioids for chronic pain asserted that the literature contributes no evidence on efficacy because all trials had “inadequate duration.”

To explore the evidence, we examined durations of studies on opioid, nonopioid drug, and behavioral therapies for chronic pain.  

Methods. We retrieved Cochrane reviews of anticonvulsants, antidepressants, NSAIDs, opioids, or behavioral interventions for chronic pain. We also examined all opioid treatment studies retrieved for the federal evidence report but excluded due to “inadequate duration.”

Results. We graphed numbers of trials vs duration for the five treatments reviewed in the Cochrane Library, compared with durations of opioi12690d trials dropped from the federal evidence report. Most graphs were overdispersed Poisson distributions. Nearly all trials had active treatment durations of 12 weeks or less.

Conclusions. 

No common nonopioid treatment for chronic pain has been studied in aggregate over longer intervals of active treatment than opioids.

To dismiss trials as “inadequate” if their observation period is a year or less is inconsistent with current regulatory standards.

The literature on major drug and nondrug treatments for chronic pain reveals similarly shaped distributions across modalities.

Considering only duration of active treatment in efficacy or effectiveness trials, published evidence is no stronger for any major drug category or behavioral therapy than for opioids.

© 2016 American Academy of Pain Medicine.  

The full article details how the CDC’s conclusions are based on studies selected by using arbitrary non-standard standards of inclusion/exclusion.

Introduction

The use of opioids began in prehistory and is now standard practice in much of the world for the management of acute, chronic, and cancer-related pain.

Balancing the legitimate medical use of opioids for analgesia vs society-wide abuse, misuse, diversion, addiction, and mortality has become a major public health theme.

In March 2016, the US Centers for Disease Control and Prevention (CDC) published a guideline for prescribing opioids for chronic pain on the CDC website.

An important message communicated in the CDC guideline and related press releases is that the body of evidence addressing the effectiveness or efficacy of opioid therapy for outcomes of pain, function, or quality of life was insufficient to contribute any studies for their analyses.

In reaching this conclusion, the minimal duration for inclusion of a long-term study was set by the authors as “>1 year,” the same threshold employed by a 2014 evidence report that informed the 2016 CDC guideline.

The same consultant was the lead methodologist for both the 2014 evidence report and the 2016 CDC guideline.

However, earlier systematic reviews of the effectiveness or efficacy of opioids for chronic noncancer pain, co-authored by the same consultant and based upon the best available evidence, had identified dozens of clinical trials and systematic reviews of this topic.

Although their conclusions were guarded due to the poor overall quality of the literature, both earlier reviews concluded that selected, carefully monitored patients might benefit from such therapy.

Because the 2016 CDC literature review may be viewed as an update of the earlier reviews, it was striking that the 2016 review reached far more negative conclusions about the risk-benefit ratio for long-term opioid therapy than did the 2009 and 2010 reviews.

The 2014 evidence report and the 2016 CDC guideline relied upon the absence of studies of a year or greater duration to advance recommendations reflecting a low perceived benefit-to-risk ratio of opioid use for chronic pain.

And that is how they justified opioid prohibition.

We wondered whether a more standard approach to study retrieval and inclusion would confirm or refute this perception. Issues related to study inclusion also have implications for switching from or preferring one therapy to another

In addition, we examined studies cited in in the Cochrane Library of Systematic Reviews addressing opioids, antidepressants, anticonvulsants, NSAIDs, and behavioral treatments.

Our objective was to assess whether differences exist between the duration of treatment trials for chronic pain using each of these modalities, if analyzed without applying the one-year minimum threshold for inclusion newly introduced in the 2014 AHRQ and 2016 CDC reports.

Discussion

We conducted an investigation of the nature of the evidence for five frequently used interventions for chronic pain recommended in the 2016 CDC guideline for opioids in chronic pain:

pharmacotherapies (anticonvulsants, antidepressants, NSAIDs, and opioids) and nondrug, behavioral interventions

Our motivation for doing so was curiosity as to why the 2014 AHRQ evidence review and 2016 CDC guideline for the use of opioids in chronic pain declared that no suitable studies of opioid therapy qualified for inclusion.

Earlier systematic reviews in which one or more coauthors of the 2014 AHRQ evidence review and 2016 CDC guideline had participated, had identified sufficient studies to conclude, albeit guardedly, that selected patients carefully followed might benefit from such therapy.

Because the principal reason for the 2014 and 2016 documents’ exclusion of all retrieved effectiveness and efficacy trials was stated as “inadequate duration,” we focused our analysis upon the durations of active treatment in published clinical trials of all six modalities for chronic pain

Is it justified to state, as did the 2014 AHRQ evidence report and the 2016 CDC guideline, that there are no trials of opioid therapy whose duration is adequate to inform clinical guidelines on chronic pain treatment?

No.

Both the AHRQ and Cochrane opioid literatures have longer durations than corresponding literatures for anticonvulsant, antidepressant, NSAID, and behavioral therapies

Thus we found no evidence for the statement that currently available literature on opioid efficacy and effectiveness are inadequate to provide clinical guidance

Further, if a one-year minimum threshold for duration of active treatment were required to justify using any of the major typical therapies for chronic pain, then none of these nonopioid therapies could be recommended.

Insofar as strength of the recommendation to switch from an opioid to a nonopioid therapy was based upon the durations of active treatment in the corresponding clinical trials, the published literature is insufficient to recommend any switch from one modality to another.

Conclusion

To categorize analgesic trials as of “inadequate duration” if their observation period is a year or less is a major departure from existing standards for the duration of published treatment trials for chronic pain, the vast majority of which are 12 weeks or less.

However, basing therapeutic decision-making upon durations of published clinical efficacy or effectiveness trials does not support choosing any drug or nondrug therapy over another.

In fact, the opening words of the first recommendation of the CDC guideline (“Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain”) and the rationale presented directly below it make no mention of the overwhelmingly strong evidence for significant morbidity and mortality risk from the most likely nonopioid alternatives to opioid therapy for chronic pain: NSAIDs, coxibs, and acetaminophen.

The morbidity and mortality likely to result from an increased population-wide consumption as a consequence of following this recommendation are difficult to estimate but likely to be of the same magnitude as from opioids.

Safety concerns about these nonopioid alternatives are sufficiently compelling as to have prompted the US FDA to issue its latest of many NSAID safety warnings in a 2015 “Drug Safety Communication”.

In the future, as more population-based information becomes available to fill existing research gaps, clarifying the selection and maintenance of patients who may benefit from opioid therapy or other drug or nondrug interventions to control chronic pain must be a high priority.

See more on this problem: CDC Scientists Expose Agency Corruption

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Addendum 12/5/16

At that time of this post, this full article was online and freely accessible, so I was dismayed to hear from a comment that as of Dec 5, the full article was behind a paywall.

I verified that my annotations from the full version of this article were collected on Nov 28 from the link at the top of this post: http://classic.painmedicine.oxfordjournals.org/content/17/11/2036.full

Now the price to see the full article is astonishingly high, making it virtually inaccessible to most of us:

A subscription (12 issues) to the “Pain Journal” where it was published costs $1047.00, but you may access the article for 1 day for US$40.00.