The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) is a major group providing guidance for design considerations of acute pain clinical trials. IMMPACT is made up of a team consisting of some of the most respected researchers and clinicians in the field of pain medicine. As of 2016, IMMPACT recommends these ten best practices in acute pain analgesia trials:
1. Studies should include both a placebo arm and an active comparator.
While a vital part of analgesic trial design, using a placebo arm can raise a number of ethical concerns. These can be addressed by:
- Clearly explaining the placebo’s use in informed consent materials
- Educating and training patients and site staff about the inclusion of placebos in study design
- Ensuring effective rescue medication is available for additional pain relief upon patient request
In practice, the inclusion of an active comparator arm will depend on the type of drug being studied. Active comparators may not always be necessary for reformulations of approved drugs. However, active comparators may be needed to determine efficacy in comparison to less expensive, generic versions of the drug. Study designers should include an active comparator whenever possible.
2. The active comparator must be appropriate for the specific study.
For novel drugs or “new chemical entities,” at least one active comparator is required. In the absence of established standards, as in very early phases, the comparator should have a mechanism of action similar to the study drug. For investigational drugs with a unique mechanism of action, it is ideal to include two or more active comparators, each with a different mechanism of action (e.g., an opioid and a nonsteroidal anti-inflammatory agent). For studies intended to meet regulatory requirements, the active comparator should be a drug that is already approved for the target indication.
3. Randomized treatment allocation should be used.
Randomized treatment allocation is typically done through parallel group designs, as crossover design is not typically recommended for acute pain settings.
4. A sufficient amount of baseline pain must be established.
Baseline pain intensity must be moderate to severe before the initial dosing. Sponsors may consider patient stratification according to differences in baseline pain.
5. Numeric rating scales for pain intensity or relief should be included.
These measurements are simple to perform quickly in a clinical setting. Alternative measures, such as verbal rating scales and visual analog scales, may have lower sensitivity.
6. Multiple early observation times should be scheduled.
Quick pain relief is needed for the acute treatment setting. Many assessments during the first one to two hours are useful for establishing analgesic onset profiles.
7. All adverse events must be collected and reported.
These events should be recorded as they occur and must be described in detail.
8. All study participants must be treated with identical regimens.
This includes identical surgical, anesthetic, and perioperative care regimens. Predetermined scripts may be useful for interviewing and communicating with study participants.
9. The same coordinator should be assigned to a patient throughout the study period whenever feasible.
The study environment should be controlled as much as possible; continuous care through study coordinators helps to ensure consistency.
10. Trained study personnel should be employed.
All clinicians involved in conducting the trial and related care should be thoroughly trained in its methodology.