Table 1.

Research design considerations for acute pain

Study objective	Primary outcome	Advantages	Challenges
1. Prevent use of opioids for acute pain	Opioid use (yes/no)	• Clinically meaningful – if patients never start opioids they will not misuse them or experience opioid-related adverse outcomes. • Short duration / little missing data.	• Could fail to identify an efficacious treatment by setting the bar for “treatment success” too high, especially in the case of major surgery or trauma.
2. Reduce opioid dosages for acute pain	Opioid dosage (measured via PCA or hospital records)	• Continuous opioid dosage generally has more power than dichotomous (i.e., yes/no). • Dose not require complete absence of opioid use for “success”, thus potentially more relevant for major surgeries or trauma. • Short duration / little missing data.	• Little data available to determine clinical meaningfulness of different decreases in opioid dosages.
3. Reduce opioid-related adverse outcomes in acute pain	Adverse outcomes measured via passive or active data collection	• Arguably more clinically meaningful than decreasing opioid dosages. • Short duration / little missing data.	• Research is necessary to understand which adverse outcomes are most important for different populations and how to combine them into a single endpoint.
4. Eliminate the need for opioid prescription at hospital discharge for acute pain after surgery or trauma that would usually require one	Opioid prescription at discharge (yes/no)	• Clinically meaningful -- if patients do not go home with an opioid they are unlikely to become dependent. • Data recorded by research staff.	• Could fail to identify an efficacious treatment by setting the bar for “treatment success” too high, especially in the case of major surgery or trauma, although less so than for eliminating opioid use all together.
5. Decrease the duration of opioid use after surgery or acute pain problem	Duration of opioid use	• Continuous outcome that generally has more statistical power than dichotomous outcome. • No need to identify one specific time by which to eliminate opioid use.	• Little data available to select a clinically meaningful change in duration. • Longer follow-up provides more opportunity for missing data and requires more resources. • Measurement of at-home opioid use has more opportunity for error than opioid use measured in the hospital.
6. Reduce incidence of opioid use 3 months after surgery or acute pain problem in opioid-naïve patients.	Opioid use 3 months after acute pain problem	• Preventing longer-term opioid use is highly clinically meaningful. • For most surgeries or trauma, the physical tissue damage should be healed within 3 months, avoiding the problem of this outcome potentially being a “too high bar” like eliminating opioids altogether or leaving the hospital without opioids.	• With current opioid prescribing practices, few patients may be prescribed opioids 3 months after an acute pain problem, leading to relatively low power / large required sample sizes for this objective. • Measurement of at-home opioid use has more opportunity for error than opioid use measured in the hospital.

The population for these research objectives would include patients who have acute pain from recent surgery or trauma that would generally require opioid treatment. PCA patient controlled analgesia