Towards an international expert consensus for defining treatment response, remission, recovery and relapse in obsessive‐compulsive disorder
Authors: David Mataix‐Cols, Lorena Fernández de la Cruz, Ashley E. Nordsletten, Fabian Lenhard, Kayoko Isomura, Helen Blair Simpson
Journal: World Psychiatry (2016)

Marked inconsistencies exist in how treatment response, remission, recovery and relapse are defined in clinical trials for obsessive-compulsive disorder (OCD). This impairs the comparability of results and communication in the field. Empirical methods (e.g., signal detection analyses) have been used to calculate the optimal amount of symptom improvement to classify an individual as a "responder" or "remitter", both in adults1-4 and children5 with OCD. Unfortunately, this has led to different recommendations. The concept of "recovery", used in other mental disorders such as depression6, is rarely used in the OCD literature. "Relapse" has been defined in some OCD studies as a return to pre-treatment symptom levels and in others as a worsening of symptoms to a certain degree7. These inconsistent definitions make comparisons across studies and treatment modalities challenging, and have led to different estimates of treatment efficacy and relapse risk8. The Reliable Change Index9, a scale-standardized metric often used to alleviate this issue, also has limitations, including the inability to use relevant normative samples across studies, leading to different severity cut-off scores10. Since these constructs are man-made rather than natural entities, expert consensus may be a more appropriate approach to their definition. However, previous proposals7 have not been met with wide acceptance. A broader, international, multidisciplinary consensus can create investment in standardization and motivate field-wide adoption of the resulting definitions. Here we describe the results of a multi-round, web-based Delphi survey11, the aim of which was to facilitate a global, expert consensus regarding the conceptual and operational definitions of treatment response, remission, recovery and relapse for use in clinical trials of OCD. First, second, last and corresponding authors of international peer-reviewed OCD papers published between 2007 and 2013 were invited to participate. Participants included mainly psychologists and psychiatrists with expertise in pediatric and/or adult OCD. In a first round, participants were presented with conceptual definitions of treatment response, remission, recovery and relapse adapted from the depression literature6 and different ways to operationalize them, and were asked with which they agreed. Two comments are worth adding. First, in Round 1, to consider a patient a treatment responder or remitter, many experts (56% and 58%, respectively) thought that sustained improvement should be present for at least one month. However, this proposed duration clashes with the (C)Y-BOCS, which asks about symptoms during the "previous week". In addition, response has been defined in most prior OCD trials at the end of treatment. In Round 2, despite explicating this, only 64% and 46% of experts agreed with the proposal of "at least one week" for the duration of response and remission, respectively. To accommodate this disagreement in the field, the duration for response and remission above allows for "at least one week" and we recommend additional follow-up assessments where possible to assess whether response/remission status has been maintained over longer periods. Second, to judge that a patient relapsed, many experts (Round 1: 48%; Round 2: 87%) thought that worsening of symptoms should be present for at least one month to protect against transient flares in symptoms. However, some patients acutely deteriorate and require immediate clinical intervention12. For this reason, the relapse definition above indicates that patients who need to be removed from treatment protocols before one month because of worsening of OCD symptoms should also be considered to have relapsed. In summary, agreement was reached on how to define response, remission, recovery and relapse across a range of international professionals with expertise in OCD. We recommend that researchers report their results using these definitions whenever possible. As outlined by Frank et al6, doing so will lead to: a) improved design, interpretation and comparison of clinical trials of various modalities; b) improved communication of research findings between professionals and to the general public; c) improved guidelines for evaluation of clinical efficacy of various treatments by regulatory agencies; and d) development of improved treatment guidelines for clinical practice. David Mataix-Cols1, Lorena Fernández de la Cruz1, Ashley E. Nordsletten1, Fabian Lenhard1, Kayoko Isomura1, Helen Blair Simpson2,3 1Centre for Psychiatric Research and Education, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 2Columbia University Medical Center, Columbia University, New York, NY, USA; 3New York State Psychiatric Institute, New York, NY, USA The authors thank all participating colleagues for their enthusiastic response to the survey and their helpful insights. A full report on the survey is available from D. Mataix-Cols upon request.