Optimizing Delivery of a Behavioral Cancer Pain Intervention Using a SMART

摘要：癌症患者经历着巨大的疼痛，并报告说疼痛是他们最痛苦的 症状。癌症患者中重度疼痛的发生率保持在50%以上。 在随机临床试验(RCT)中，对癌症疼痛的行为干预已经证明是有效的，但 继续在临床上未得到充分利用。通过生成对癌症疼痛的行为干预优化 最佳剂量的证据(例如，会话次数、教授的技能)、干预顺序和个人 与剂量-反应相关的特征可以改善行为癌症疼痛干预的实施。 我们建议使用一种新的对照临床试验设计，即序贯多分配随机试验 (SMART)，以检查对不同剂量的行为癌症疼痛干预的反应(疼痛应对技能 培训[PCST])和随后基于反应的剂量调整。癌症疼痛患者(N=327) 最初将随机接收PCST-FULL或PCST-Brief。未回复的参与者(&lt；30% 疼痛减轻)至其初始分配的干预将被重新随机化以接受维护(即， 强化课程侧重于解决问题和技能强化)或提高干预水平 (即额外的课程、技能)。对最初分配的任务有反应(减少30%疼痛)的参与者 干预将被重新随机分为维持量或不再进一步治疗。这项研究的目的 目的是：1)提供对不同初始剂量PCST反应的比较证据；2)提供比较 根据患者反应调整PCST干预剂量序列的证据；3)确定患者 在每次剂量后，对PCST的第一次和第二次剂量的中等反应的特征 6个月的随访，并制定出最优的适应治疗策略，使初始和 根据患者特点进行二次干预；4)评估是否使用一次PCST剂量 而基于初始反应的后续PCST剂量是一种成本效益高且实用的PCST方法。 假设是：1)与PCST-Brief相比，PCST-Full将产生显著更大的止痛效果； 专门的智能分析将比较独特的PCST干预序列，识别 更大程度地减少疼痛；3)患者特征(即疼痛干扰、癌症分期、疼痛 灾难)将缓和参与者对初始和二次干预剂量的反应，并且可以 用于制定选择干预剂量的最优自适应策略；4)该方法的实用性 将通过干预的成本效益和成功的总体应计来证明PCST的交付， 受试者保留率高，干预方案依从性高。这个项目意义重大，因为它将 增强我们为癌症患者提供行为癌症疼痛干预的能力，以更好地匹配他们的 需要和特点，最终改善执行，减少痛苦和痛苦。

Abstract: Patients with cancer experience significant pain and report pain to be their most distressing symptom. The incidence of moderate to severe pain in patients with cancer remains greater than 50%. Behavioral interventions for cancer pain have demonstrated efficacy in randomized clinical trials (RCT), yet continue to be clinically underutilized. Optimizing behavioral interventions for cancer pain by generating evidence on optimal dosage (i.e., number of sessions, skills taught), intervention sequencing, and personal characteristics related to dose-response can improve implementation of behavioral cancer pain interventions. We propose using a novel controlled clinical trial design, a sequential multiple assignment randomized trial (SMART), to examine response to differing doses of a behavioral cancer pain intervention (Pain Coping Skills Training [PCST]) and subsequent response-based adjustments to doses. Cancer patients with pain (N=327) will initially be randomized to receive either PCST-Full or PCST-Brief. Participants who do not respond (<30% pain reduction) to their initially assigned intervention will be re-randomized to receive either maintenance (i.e., booster sessions focused on problem solving and skills reinforcement) or an increased level of intervention (i.e., additional sessions, skills). Participants who respond (> 30% pain reduction) to their initially assigned intervention will be re-randomized to either a maintenance dose or no further treatment. The aims of the study are to: 1) provide comparative evidence of response to differing initial doses PCST; 2) provide comparative evidence of intervention dose sequences of PCST that adjust based on patient response; 3) determine patient characteristics that moderate responses to initial and secondary doses of PCST following each dose and at a 6-month follow up and derive an optimal adaptive treatment strategy for personalizing selection of initial and secondary interventions based on the patient characteristics; 4) evaluate whether using primary PCST doses and subsequent PCST doses based on primary response is a cost-effective and practical approach to PCST. Hypotheses are: 1) PCST-Full will produce a significantly greater reduction in pain compared to PCST-Brief; 2) specialized SMART analyses will compare unique PCST intervention sequences identifying sequences that produce greater reductions in pain; 3) patient characteristics (i.e., pain interference, cancer stage, pain catastrophizing) will moderate participant responses to the initial and secondary intervention doses and can be used to develop an optimal adaptive strategy for selecting intervention doses; 4) practicality of this approach to PCST delivery will be demonstrated by cost-effectiveness of the intervention and successful overall accrual, high subject retention, and high intervention protocol adherence. This project is significant because it will enhance our ability to provide cancer patients with behavioral cancer pain interventions that better match their needs and characteristics, ultimately improving implementation and reducing pain and suffering.