Correcting FDA Questions about Drug-Seeking

Evaluation of US Food and Drug Administration-recommended abuse-potential questions in chronic pain patients without history of recreational opioid use: results and plan for research – free full-text /PMC6301309/ – Dec 2018

Background

Existing patient-reported outcome (PRO) assessments that measure the human abuse potential for opioid analgesics have been tested exclusively in experienced recreational opioid users, as required by US Food and Drug Administration (FDA) guidance.

Methods

The goals of the current studies were to modify items from FDA-recommended abuse potential PRO assessments to specify the analgesic benefits versus the euphoric effects of opioids and to ascertain the clarity, understandability, appropriateness, and validity of the modified questions. 

This was achieved by conducting cognitive debriefing interviews (CDIs) with patients (≥18 and <65 years) who

  • have chronic pain,
  • were prescribed an opioid daily dose of at least 80 morphine-equivalent milligrams (>30 days to ≤180 days from the date of interview), and
  • did not have a history of recreational opioid use.

Results

Participants in study 1 (n=30) and study 2 (n=7) had a better understanding of the items designed to measure the concepts of drug liking and items designed to measure the desire to take a drug again when reasons for liking and desire to take again were included in the item wording (namely, “due to pain relief ” and “excluding pain relief ”).

Most participants indicated no interest in taking their medication for reasons other than pain relief.

I’m glad they found this fundamental truth about pain patients taking opioids. We take them for pain, and only enough to make it bearable, not for some euphoric “high” that we don’t even experience.

Conclusion

Modification of questions in the PRO assessment improved patient understanding of “drug liking” and “desire to take again.”

Patients with chronic pain who were not recreational opioid users understood the difference between the analgesic and euphoric effects of an opioid drug.

The modified questions should assist future researchers in providing a more accurate assessment of the abuse potential of an opioid, as required by regulatory agencies.

Introduction

During the safety evaluation of a new drug in development for approval, the Food and Drug Administration (FDA)’s “Assessment of abuse potential of drugs: guidance for industry” requires that the abuse potential of a drug be assessed in subjects who are experienced recreational users and who are able to “… demonstrate a meaningfully different response from that produced by placebo.

I’d really like to know where they find these “experienced recreational users”.

Do they walk down streets in cities looking for them? Do they have to be using opioids or can they be users of other drugs?

How can the government use them as research subjects when they are committing a crime (ingesting illicit or at least not prescribed drugs)? Do they get arrested afterward? Does this go on their criminal record?

To date, patient-reported outcome (PRO) assessments that measure the human abuse potential for opioid analgesics (including the Drug Effects Questionnaire [DEQ]) have been tested primarily in recreational opioid users, as required by the FDA guidance.

Measuring the abuse potential of opioids in recreational users provides useful information; however, opioid analgesics are approved by the FDA for the treatment of pain and are not intended for recreational drug use.

Therefore, accurately assessing abuse potential in nonrecreational users is important, but may be difficult when using PRO assessments developed for use with recreational users.

Given the current high rates of opioid-use problems and opioid overdoses reported in health care delivery systems,accurately assessing abuse potential in nonrecreational users is of the utmost importance.

In addition to the DEQ, commonly used measures in assessing opioid-abuse potential in clinical studies include:

  • the 100 mm Drug-Liking Visual Analogue Scale (DL-VAS)5
  • the 100 mm Overall DL-VAS (ODL-VAS)5
  • the Severity of Dependence Scale (SDS)6
  • the Drug Abuse Screening Test (DAST10).7

The DL-VAS and ODL-VAS are qualitative scales recommended to assess opioid-abuse potential in clinical trials focused on reports of drug liking and feeling high

While these instruments have been successfully used with recreational drug users, they may cause confusion and produce misleading results when administered to patients taking opioid analgesics for pain management without clarifying contextual information

For example, current VAS items may confuse the euphoric effects of the opioid with the analgesic benefits of the medicine.

These scales may not be able to distinguish a patient’s liking a drug for pleasure from liking a drug for pain relief.

Patients with chronic pain who experience poor pain management often exhibit behaviors consistent with addictive behaviors that can further confound PRO assessments, such as

  • a focus on drug seeking,
  • requesting medication prior to scheduled dosing,
  • requesting specific opioids, and
  • anxiety about future medications

Therefore, legitimate requests for opioids with the distinct purpose of relieving chronic pain can be confused with drug-seeking behavior for abuse.

This should be required reading for all the anti-opioid zealots who insist we are taking our prescribed opioids only to avert withdrawal, not to treat pain.

There is an important and unmet need for proper validation of these PRO instruments in a population of patients diagnosed with chronic pain who do not have a history of opioid recreational use.

Modification of any unclear scales or items regarding opioid-abuse potential in clinical trials and observational studies may help to determine more accurately the reasons for a patient endorsing liking of an opioid and wanting to take the drug again, particularly whether the opioid is being used for pain relief, or for reasons other than pain relief

Two sets of cognitive debriefing interviews (CDIs) with patients who had chronic pain and were not recreational opioid users were conducted. 

Patients evaluated standard abuse-potential PRO assessments and additional VAS items that were designed to distinguish the analgesic benefits vs the euphoric effects of the opioids to ascertain the

  • clarity,
  • understandability,
  • appropriateness, and
  • validity

of these scales and modified items in patients taking opioid analgesics for pain management, consistent with debriefing methods commonly used in survey research

New VAS items

The original DL-VAS and ODL-VAS were augmented with six new items. The VAS item “I would take this drug again” was used as a model to create the following new items:

  • “I would take this drug again for pain relief ”
  • “Excluding pain relief, I would take this drug again.”

The response option used for the original item, a 100 mm scale ranging from “Definitely not” to “Definitely so,” was unaltered.

Similarly, the items “At this moment, my liking for this drug is?” and “Overall, my liking for this drug is?” were used as models to create the following new items:

  • “At this moment, my liking for this drug due to pain relief is?”
  • “At this moment, excluding pain relief, my liking for this drug is?”
  • “Overall, my liking for this drug due to pain relief is?”
  • “Overall, excluding pain relief, my liking for this drug is?”

The response option for these four items remained a 100 mm scale ranging from “strong disliking” at the 0 mm mark to “neither like nor dislike” at the 50 mm mark to “strong liking” at the 100 mm mark.

Table 1 shows select statements from cognitive debriefing interviews

Participant statements:

In response to items assessing desire to take drug again:

• “Well, I mean I would take it again definitely for pain reasons and just pretty much pain reasons.”
• “If it wasn’t for the pain relief, I would not be taking it.”
• “I only want to take it for pain, so I would not take it for anything outside of pain.”
• “Would I take it only for pain relief if it had no attachment of euphoric feeling? Yes, I would.”

In response to items assessing likability of drug:

• “Now, this one says: ‘At this moment, excluding pain relief, my liking for the drug is…”, and I put ‘neither like nor dislike, because, really, for pain, it’s the only reason that I need it, so there’s no other reason to take it.”
• “This one I can say clearly is that it’s a matter of if I’m not taking it for pain, I have no dislike or like for it.”
• “I’m trying to think: the ‘like’ or the ‘not like’? Sometimes you take stuff whether you like it or not.”
• “That’s mainly why I’m taking the drug, not to try to get any other kind of feeling. I just want it to take away my pain, my knee pain.”

Study 2

DL-VAS and ODL-VAS

Similarly to study 1, the VAS was generally intuitive and easy for participants to use.

The new item “I would take this drug again for pain relief ” was described as “straightforward,” easy to comprehend, and respond to.

Participants were also able to clearly interpret the more complex items containing the “excluding” phrase, such as “Excluding pain relief, I would take this drug again.”

SDS

Overall, participants felt confident responding to the SDS items. However, several issues were identified that led some participants to feel somewhat confused or unsure about their meaning.

Item 1: Do you think your use of drug X was out of control?

Participants believed that being out of control meant they were unable to or unwilling to use the medication as intended and lacked the control to change their behavior.

Participants questioned why they would be asked to consider being out of control for a medication they were using according to their prescriptions.

Yes, the problem isn’t just the question, it’s why the question is even being asked.

Item 2: Did the prospect of missing a fix (or dose) make you anxious or worried?

The word “fix” was both confusing and disturbing to some participants.

“Fix” is strongly associated with illicit drugs, whereas “dose” indicates medication.

Because they were responding about their use of pain medication, participants suggested the word “fix” be removed.

A couple of participants were somewhat offended by the apparent implication that they were using illegal drugs, rather than taking medication.

One participant completed the questions with the frame of reference that she was being asked about illegal drug use, rather than the pain medication she was relying on.

This item was easy to read and understand,

Item 3: Did you worry about your use of drug X?

This item was easy to read and understand, although some participants questioned why they would worry about their pain medication, as they were following the instruction of their prescribing doctor.

Again, this question is clearly not applicable to patients following doctors’ orders.

Item 4: Did you wish you could stop?

There was confusion among participants about the intent of this item.

One interpretation was that the item was referring to an inability to stop taking the medication because the subject had become dependent on the medication beyond that needed to manage the pain.

This interpretation was somewhat bothersome for those who had already concluded the items were not interested in their use of legal, prescription medication.

A second interpretation was that the item may have been referring to the ability to stop taking the pain medication because the participant no longer experienced pain. With this second interpretation, participants considered responding in the affirmative.

Item 5: How difficult did you find it to stop or go without drug X?

As participants were still taking their medication, they believed that part of the question (about stopping) was irrelevant.

Participants considered how difficult they thought it might be for them to go without their medication, given their current pain.

DAST10

This instrument was considered easier and more natural for participants to complete. Several commented that the questions were “natural” and “straightforward.” Even so, a few items presented a few challenges for participants.

Item 2: Do you abuse more than one drug at a time?

Participants did not believe they were abusing any drug; including the pain medication they were currently using.

The implication that participants were abusing their medication was somewhat offensive in general.

Furthermore, a negative response did not accurately portray the fact that they were not abusing any drugs, just that they were not abusing more than one.

This is like the TV detective’s trick question: “Which of your victims did you hate the most?” No matter the answer, the implication remains that the subject had multiple victims.

Item 3: Are you always able to stop using drugs when you want to?

The composition of this item was awkward.

Participants were hesitant to stop taking their medication because of their pain.

Discussion

The results of the current study should be considered when designing future studies that evaluate the abuse potential of opioid analgesic drugs in patients with chronic pain who are nonrecreational opioid users

Conclusion

This study showed that modification of questions in PRO assessments improved patient understanding of the concepts “drug liking” and “desire to take again.”

This study appropriately targeted the population for which the drug was intended (ie, patients with chronic pain with no history of recreational drug use).

By comparison, the SDS presented conceptual issues for these nonrecreational opioid-use patients, because this scale was developed for and normed on substance-abusing populations.

The results of this study suggest that these patients understand the difference between the analgesic and euphoric effects of an opioid drug, and that the modified assessments will assist researchers in providing a more accurate assessment of the abuse potential of an opioid, as required by regulatory agencies.

1 thought on “Correcting FDA Questions about Drug-Seeking

  1. peter jasz

    ( RE: I’m glad they found this fundamental truth about pain patients taking opioids. We take them for pain, and only enough to make it bearable, not for some euphoric “high” that we don’t even experience.)
    So, so true: “… not for some euphoric “high” that we don’t even experience.”

    A couple things:
    1) these same tests/policies/policy makers come from those who likely abuse drug/alcohol far more than those “filling out” these forms.
    The funny (sad in fact) thing is, this “research” is 50 years old. If not 100. People, please; corporate/governmental America are playing with you/me. Please understand that. ,

    When I finally see, hear and read about the corrupt abuses dished out by these psycho’s facing criminal charges, jail time -and taking their own lives in shame/disgrace, I’ll earnestly rejoin -and rejoice !

    pj

    Liked by 1 person

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