Friday, June 25, 2021

Scholars at 14th GRADE Workshop Discuss the Unique Challenges of Sparse Evidence, Guideline Collaborations, and Financial Incentives in Healthcare

During the 14th GRADE Guideline Development Workshop held virtually last month, the Evidence Foundation had the pleasure of welcoming three new scholars with the opportunity to attend the workshop free of charge. As part of the scholarship, each recipient presented to the workshop attendees about their current or proposed project related to evidence-based medicine and reducing bias in healthcare.

This spring's lot of three scholars was nothing short of incredibly impressive. Ifeoluwa Babatunde, a PhD student in clinical research at Case Western Reserve University, discussed the unique challenges of developing a guideline on the management of patients undergoing patent foramen ovale (PFO) closure for the Society for Cardiovascular Angiography and Interventions (SCAI). The synthesis of evidence for this question is hampered by controversies and limited evidence as well as complications due to comorbidities and age differences in the populations of interest. Babatunde discussed her interest in attending the workshop to learn more about the appropriate use of observational and indirect evidence to better answer questions related to PFO closure.

"The GRADE workshop helped me to see systematic review methodology from a deeper and more critical perspective," said Babatunde. "GRADE offers a very comprehensive yet succinct and transparent framework for developing and ascertaining the certainty of evidence in guidelines. Hence I feel better equipped to tackle challenges that arise from creating reviews and guidelines regarding conditions and populations with sparse RCTs."

Next, Dr. Pichamol Jirapinyo, the Director of Bariatric Endoscopy Fellowship at Brigham and Women's Hospital and instructor at Harvard Medical School, discussed her work on an international joint guideline development effort between the American Society for Gastrointestinal Endoscopy (ASGE) and the European Society of Gastrointestinal Endoscopy (ESGE) to produce recommendations for endoscopic and bariatric metabolic therapy (EBMT) in patients with obesity. EBMT is one of several possible management routes for obesity, alongside pharmacological and surgical options. The project will aim to answer several questions, including how patients should be managed before and after EBMT, and regarding the safety and efficacy of both gastric and small bowel EBMT.

“The GRADE workshop provided me a great framework on how to apply GRADE methodology to systematic review and meta-analysis to rigorously develop a guideline," said Dr. Jirapinyo. 'In addition to learning about the GRADE methodology itself, I found the workshop to be tremendously helpful with providing practical tips on how to run a guideline task force successfully and efficiently.”  

Finally, Dr. Lillian Lai, a research fellow in the Department of Urology at the University of Michigan, presented an intriguing discussion of financial incentives in clinical decision-making in urology. The surveillance and management of localized prostate cancer, for instance, has several different options ranging from active surveillance (which is less costly) to prostatectomy (which is more costly). Regardless of the reported health outcomes of these approaches, there is little financial incentive to conduct surveillance as opposed to surgery. The project's goal is to use health services research methods to understand how urologists response to large financial incentives, and then create financial incentives and remove financial disincentives for the promotion of guideline-concordant practices. 

"I gained invaluable knowledge on how to use the GRADE approach to rate the certainty of evidence and strength of recommendations," said Dr. Lai. "Going through the guideline development tool with experts in small groups was particularly useful for me to understand what a guideline recommendation means and entails. This workshop came at a critical time in the backdrop of COVID, and the ever-changing landscape of medicine where patients and providers need to make timely and informed decisions together."

If you are interested in learning more about GRADE and attending the workshop as a scholarship recipient, applications for our upcoming virtual workshop in October are now open. The deadline to apply is July 31, 2021. Details can be found here. 

Wednesday, June 9, 2021

Evidence Foundation scholar spotlight: Georgios Schoretsanitis

Last fall, Dr. Georgios Schoretsanitis attended the 13th (and first-ever virtual) GRADE guideline development workshop as a scholar of the Evidence Foundation. As such, he presented to the rest of the workshop attendees on his work developing guidelines for therapeutic drug monitoring to optimize and tailor treatment for psychotherapeutic medications. Beginning in 2017, a series of recommendations for reference ranges for two commonly prescribed antipsychotic medications was developed, followed this year by an international joint consensus statement on blood levels to optimize antipsychotic treatment in clinical practice.

Dr. Schoretsanitis now has an exciting update on his project.

"My main research interest is therapeutic drug monitoring, also known as TDM, which refers to the quantification and interpretation of medication levels in the blood (plasma or serum) of the patient treated with psychotropic agents," says Dr. Schoretsanitis. "The aim of TDM in clinical practice is to improve treatment response and safety outcomes. Apart from analyzing TDM clinical routine data, I have also been working as a member of the TDM taskforce of the German Association of Neuropsychopharmacology and Phaarmacopsychiatry (Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmacopsychiatrie; AGNP) involved in systematic reviews of TDM literature, which provide so-called therapeutic reference ranges for medication levels. These ranges may orient clinicians during dose selection. Attending the virtual GRADE workshop in October 2020 provided me much of inspiration, but also knowledge of well-established methodological tools for the assessment of quality of evidence.

Hereafter, in the TDM task force of AGNP, we adopted a GRADE-oriented approach in assessing TDM literature as we are reviewing new TDM evidence on commonly prescribed antipsychotics under the supervision of Prof. Gerhard Gründer, Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. This type of approach is more standardized and follows GRADE guidelines. Ultimately, this work will enhance methodological rigidity for the next Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology [last update 2018; Hiemke et al, Pharmacopsychiatry]. I strongly encourage researchers involved in systematic reviews or assessment of evidence quality to attend the GRADE workshop which enables a major upgrade of related skills and knowledge."

Stay tuned for future updates from other past Evidence Foundation scholars like Dr. Schoretsanitis and the exciting work they are doing to improve the application of GRADE methodology and evidence-based medicine.

If you are interested in learning more about GRADE and attending the workshop as a scholarship recipient, applications for our upcoming virtual workshop in October are now open. The deadline to apply is July 31, 2021. Details can be found here. 

Thursday, June 3, 2021

The Systematic Survey Behind a Collection of Minimal Important Differences (MIDs) Across the Patient-Reported Outcome Literature

Patient-reported outcome measures, or PROMs, allow clinicians and researchers to directly elicit information about treatments that are important to patients, such as side effects or improvements in pain, function, or quality of life. In order to interpret changes in PROMs relative to a clinical recommendation, however, a minimal important difference (MID) - or the smallest possible change in the outcome that would mandate a change in the patient's management - must be determined.

Luckily, a wealth of published studies exist to provide a library of MIDs for a wide range of outcomes, and recently, a review published by Carrasco-Labra and colleagues synthesized these works together. The study included any empirical reports of MIDs in adolescents or adults that used an anchor-based approach, in which MIDs are based on an observed change related to an external criterion rather than the distribution of a particular patient sample. As such, anchor-based MIDs tend to be more directly applicable across patient populations. Ultimately, a collection of 585 studies reporting on 5,324 MID estimates across 526 distinct PROMs was presented.

About two-thirds (66%) collected MIDs related to patients' improvement, whereas about one-third (31%) addressed MIDs related to worsening or assumed the MIDs for improvement or worsening would be the same. Most (88%) were based on a longitudinal design in which patients' reported outcomes and satisfaction were measured at multiple timepoints. The most common types of anchors used were global ratings of change (59%), change in disease-related outcome (23%), and comparison with another group (11%), whereas the most common sources of anchor information were self-report (83%) proxy-reported (9%) and laboratory data (3%). 

MIDs are essential in interpreting the magnitude of an effect from a study or systematic review of evidence, especially when assessing imprecision as part of GRADE. They can also allow researchers to conduct "responder analyses" based on subsets of patients who experience a change in an outcome beyond a given MID. Finally, reporting mean differences in units of MIDs as part of a systematic review can standardize interpretation of an effect size in a way that may be less problematic to interpret than a traditional standardized mean difference (SMD).

The work corresponds to PROMID, a project to develop an inventory of MIDs across the literature, which can be accessed at 

Carrasco-Labra A, Devji T, Qasim A, et al. (2021). Minimal important difference estimates for patient-reported outcomes: A systematic survey. J Clin Epidemiol 133:61-71.

Manuscript available at the publisher's website here.