Randomized controlled trials have confirmed that many of the existing treatment modalities can reduce cancer-related pain on their own. However, scientific evidence related to cancer pain relief does not compare favorably with the voluminous amount of information pertaining to the usefulness and effectiveness of treatments meant for other types of serious conditions, including cancer itself. The quality of life was not evaluated uniformly in analgesic drug trials and other non-drug interventions meant for cancer pain. Limited evidence, as gathered from the retrieved trials shows that optimal analgesia helps improve quality of life. Advances made in the quality-of-life assessment and insights gained through research on consistent non-cancer related pain to understand the relationship between pain, disability and impairment provide the opportunity to better understand these interactions within the purview of cancer-related pain. Properly designed trials that have cancer pain relief as their primary outcome are required for patients who demonstrate well-defined disease and pain mechanisms. These trials must meet the growing expectations for clinical trials. High-quality trials that focus on cancer pain relief must enroll more patients for longer durations than what has been the general practice in the past; deploy blinding and active placebos whenever needed, or otherwise uniform control treatments; apply ample between-arm washout intervals and consider the state of advancing disease in crossover trials; and evaluate pain mechanisms, side-effects, and rest, occurrence, or breakthrough pain in a uniform combinable manner. Investigations pertaining to cancer-related pain and its control must seek to assess the influence that factors such as race, gender, age, ethnicity, psychosocial context, and culture have on the experience of pain and report of pain. The influence of these factors should also be evaluated during studies that focus on defining the effectiveness of specific treatments and side-effects associated with them. Drug interactions that occur during long-term treatment of cancer pain require clarification. It has not been determined whether a mechanism-based method used for diagnosing and relieving each element of pain in a patient is more effective in comparison to an empiric regimen wherein treatment administered to each patient is based entirely on the intensity of pain. Another critical question remaining unanswered is how to achieve an optimal combination of drugs and non-drug treatments, given that the latter option is considered safe and inexpensive. Although pediatric cancer pain control is important, there are virtually no analgesic drug trials that focus on children.

Data that helps assess individual differences in preferences for, responses to, and costs associated with these options provide the basis for prospective evidence-based treatments approaches to cancer pain control, but are limited. For instance, the spinal route is widely used to administer analgesics, but still there is plenty that needs to be learned about the most favorable patient selection, the comparative effectiveness of spinal drug infusion vs. systemic drug administration, and also the final selection of preliminary or secondary agents or combinations. Focusing on these fundamental questions shall improve the capability of translational clinical research in explaining the clinical significance of an ever increasing number of critical insights related to unique cancer pain mechanisms and mediators.