APA Provides Expert Testimony on Importance of Research Funding
Abstract Abstract 2965 Background: Alkylating agents have been the mainstay of multiple myeloma (MM) therapy for decades and despite introduction of several new therapies, it continues to play a significant role in its management as part of various drug combinations. While melphalan has been the most commonly used alkylator in MM, recent studies have suggested significant activity for bendamustine, a bifunctional alkylator. The combination of lenalidomide and melphalan has been associated with high response rates in relapse and newly diagnosed MM. Based on these promising results we designed a trial to evaluate the maximally tolerated dose of lenalidomide and bendamustine when used in combination as well as the efficacy of the combination in relapsed disease. Patients and Methods: Patients with relapsed MM and measurable disease were enrolled on this phase 1/2 trial provided they had not more than 4 prior lines of therapy for MM, had adequate performance status and organ and hematological function. Patients refractory to lenalidomide were allowed to enroll. The primary objectives were to (i) to determine the MTD of bendamustine and lenalidomide in combination with dexamethasone in subjects with relapsed MM (phase 1) and (ii) to evaluate the confirmed response rate of bendamustine in combination with lenalidomide and dexamethasone in patients with relapsed MM (phase 2). Bendamustine (B) was administered on days 1 and 2 of a 28-day cycle at doses of 50–100 mg/m2. Lenalidomide (R) was given days 1–21 at doses of 15–25 mg daily. Dexamethasone (D) was administered at 40 mg weekly. Dose escalation was done using a 3+3 design and MTD was defined as one dose level below that resulted in >=2 DLTS among 6 patients. The primary end point for this trial was the proportion of patients with confirmed hematologic response (sCR, CR, VGPR, or PR) over the first 6 cycles of treatment. Results: A total of 72 patients were accrued to this study from March 2010 to May 2012: 21 patients in phase 1 and 51 in phase 2. The 6 patients from the MTD dose level of phase 1 were also included in phase 2. The median age of all 72 patients was 62.1 (range, 40–86) and 57% were male. Majority (75%) of patients had previously been exposed to lenalidomide and 69% had prior exposure to bortezomib. Median # of prior therapies was 3 (range, 1–5) and 74% of patients had a prior autologous stem cell transplant. Patients have received a median of 4 cycles (range, 1–25), with 27 patients still continuing on active treatment. Disease progression led to study discontinuation in 22 (49%) and adverse events were the reason for discontinuation in 14 (31%). In phase I, two DLTs (Grade (Gr) 2 neuropathy and Gr 4 neutropenia) were seen at the highest dose level (100 mg/m2 B, 25 mg R), and the MTD was determined as 75 mg/m2 of B given days 1 and 2 and 25 mg of R days 1–21, along with D 40 mg weekly. Overall patients, 12/21 (57%) had a PR or better. In phase 2, 17 (40%) confirmed responses (>=PR) were seen among the 43 patients evaluable for response (received at least 6 cycles of treatment or have gone off study prior to 6 cycles); including 9 (21%) VGPR and 8 (19%) PR. An additional 5 patients had a minor response. Over all dose levels, a gr 3 or higher adverse event at least possibly attributed to the study was seen in 75% of patients. The most common toxicities were all hematological (thrombocytopenia and leukopenia), and most common non-hematological toxicity was infection. Prolonged time to recovery of blood counts was seen in a few patients, but majority of patients were able to tolerate the regimen with adequate dose reductions. Conclusion: The recommended dose of the combination for further studies is bendamustine at 75 mg/m2 days 1 and 2, lenalidomide 25 mg daily on days 1–21 and dexamethasone days 1, 8, 15, 22; with cycles repeated every 28 days. The regimen is well tolerated with hematological toxicity being the most common and manageable with dose reductions. The regimen is effective with high response rates and durable responses seen. Updated results with response rates and time to event analyses will be available for the entire cohort at the time of meeting. Disclosures: Kumar: Merck: Consultancy, Honoraria; Celgene: Research Funding; Millennium: Research Funding; Novartis: Research Funding; Cephalon: Research Funding; Genzyme: Research Funding. Krishnan:celgene: Consultancy, Speakers Bureau. Zimmerman:Celgene: Honoraria; Millennium: Honoraria; Novartis: Expert Testimony, Expert Testimony Other. Vij:Teva: Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Millennium: Speakers Bureau; Onyx: Honoraria, Research Funding.
Abstract Background: Among the three phenotypes of Gaucher disease (GD), type 1 is the most prevalent in the Western hemisphere, but types 2 and 3 are increasingly seen, and occur with similar prevalence to type 1 in parts of Asia. There is a spectrum of signs and symptoms among these phenotypes, which range from fatal perinatal to asymptomatic adult disease, and this heterogeneity contributes to relatively high levels of misdiagnosis and delays in diagnosis of GD. As part of the global Gaucher earlier diagnosis consensus (GED-C) initiative, we report here the signs and patient co-variables that are regarded by expert physicians as most indicative of type 3 GD in its early stages. The overarching goal of the GED-C initiative was to generate a web-based point-scoring system for use across clinical specialties to facilitate identification of patients who may benefit from diagnostic testing for GD. Methods: In an anonymous, iterative Delphi process, a panel of expert physicians was asked to provide free-text answers to a series of open questions, including: "Which unexplained signs and co-variables may be important to consider in early type 3 GD?" An independent facilitator categorized responses from round 1 into themes, which were checked and consolidated by the two non-voting co-chairs of the initiative to generate a set of summary factors. In round 2, panel members independently rated the importance of each factor using a 5-point Likert scale (1 = not important, 5 = extremely important). Factors that were assigned an importance score of at least 3 by more than 75% of respondents were provisionally classified as major; other factors were classified as minor. In round 3, panel members rated their level of agreement with the provisional classification of factors as major using a 5-point pivoted Likert scale (1 = strongly disagree; 3 = neither agree nor disagree; 5 = strongly agree). Consensus was defined as more than 67% of respondents agreeing or strongly agreeing (a score of ≥ 4) with the classification; if consensus was not reached, factors were classified as minor. Results: In total, 19 physicians with expertise in type 3 GD were recruited to the GED-C panel from 14 countries. Round 1 (100% response, n = 19) yielded 70 phrases, which were grouped into 34 themes, then consolidated as 23 factors. In round 2 (100% response, n = 19), 16 factors were provisionally classified as major. In round 3 (100% response, n = 19), consensus was reached on 10 major factors in early type 3 GD, including 9 presenting signs and 1 patient co-variable. The mean importance scores (round 2) and agreement scores (round 3) awarded to these 10 major factors are given in Table 1. Minor factors included bleeding or bruising, cardiovascular calcification, cognitive deficit, growth retardation, hyperferritinaemia, aged 18 years or younger, Jewish ancestry and a family history of Parkinson disease. Discussion: Definitive diagnostic tests for GD have been available for several years, but patient referral for testing is impeded by several issues, including a lack of knowledge among clinicians of the signs and co-variables that should arouse suspicion of GD. In type 3 GD, the problem is exacerbated by the relative rarity of the phenotype. Presenting signs and patient co-variables identified by this multidisciplinary consensus initiative will help clinicians identify those patients who may benefit from diagnostic testing for GD. Several algorithms have been devised to facilitate GD diagnosis, but non-specialists may perceive these as complex. The GED-C initiative will use the factors identified here to create a point-scoring system that clinicians of any specialty can use to obtain clear direction regarding the need to test a patient for GD. Acknowledgment: Submitted on behalf of the GED-C panel members and the European Hematology Association Scientific Working Group 'Quality of Life and Symptoms'. Administration of the GED-C initiative was funded by an unrestricted educational grant from Shire. Table 1 Mean scores of importance and agreement for 10 major factors in early diagnosis of type 3 Gaucher disease. Table 1. Mean scores of importance and agreement for 10 major factors in early diagnosis of type 3 Gaucher disease. Disclosures Kuter: Eisai: Consultancy; Genzyme: Consultancy; MedImmune: Consultancy; Rigel: Consultancy, Research Funding; CRICO: Other: Paid expert testimony; Pfizer: Consultancy; Protalex: Research Funding; GlaxoSmithKline: Consultancy; Amgen: Consultancy, Paid expert testimony; Bristol-Myers Squibb: Research Funding; ONO: Consultancy; Shionogi: Consultancy; Shire: Consultancy; Syntimmune: Consultancy; 3SBios: Consultancy. Salek:Novartis: Research Funding; Bristol-Myers Squibb: Research Funding; Shire: Consultancy; Servier: Consultancy; Sanofi: Research Funding; Agios: Consultancy. Mehta:Protalix/Pfizer: Honoraria, Other: travel grant, Research Funding; Genzyme: Honoraria, Other: travel grant, Research Funding; Actelion: Honoraria, Other: travel grant, Research Funding; Shire: Honoraria, Other: travel grant, Research Funding.
Markers of Autoimmunity in Immune Thrombocytopenia: Prevalence and Prognostic Significance
Abstract Background: Immune thrombocytopenia (ITP) is an acquired thrombocytopenia resulting from autoantibodies against platelets. Prior studies have suggested an increased prevalence of autoimmune markers in patients with ITP, even in the absence of another overt autoimmune illness. Clinical experience has suggested that there may be an association between autoimmune markers and poor outcomes in ITP but current guidelines do not encourage routine testing in ITP patients. The goal of this retrospective chart review was to investigate the prevalence of autoimmune markers and to determine if there is an association between autoimmune marker positivity and thrombosis or remission rates in patients with ITP. Methods: This was a retrospective chart review study of ITP patients who presented to one practice at Massachusetts General Hospital where a series of autoimmune markers were routinely evaluated at the time or diagnosis or referral. Included in the analysis were all patients with ITP according to ASH 2011 criteria who presented to this clinic between 1995 and 2014 and had at least one of the following autoimmune markers measured: antinuclear antibody (ANA), direct antiglobulin test (DAT), anti-thyroid peroxidase antibody (anti-ThyPeroxAb), anticardiolipin (ACL) IgM, ACL IgG, rheumatoid factor (RF), and lupus anticoagulant (LAC). Remission status was assessed at the most recent follow-up visit. Remission was defined as a platelet count greater than 30 x 109/L in a patient who was off all medications for ITP and never had a splenectomy. Patients not fulfilling both of these criteria at the most recent follow-up visit were counted as not being in remission. Thrombosis was assessed by review of the patient's radiology studies and the most recent Hematology note and included deep venous thrombosis, pulmonary embolism, embolic stroke, or lower extremity arterial embolism. Results: 169 ITP patients were identified between 1995 and 2014 who met ASH criteria for ITP and had testing for autoimmune markers. The mean age at initial evaluation was 49 years and mean duration of follow-up was 6 years. 60% of the patients were female. There is a high rate of autoimmune marker positivity in this population (Table 1). The most prevalent autoimmune markers were ANA (66%), anti-ThyPeroxAb (31%), and DAT (28%). In those subjects where all three of these tests were performed, there was significant overlap of the positive markers; out of 51 patients who had at least one positive marker, 55% had more than one positive autoimmune marker. 11% of the patients had a documented thrombosis, and 51% of the 166 patients for whom remission status was able to be ascertained achieved remission. Of the autoimmune marker tests, only the presence of anti-ThyPeroxAb was statistically significantly associated with lower remission rates, with 61% of anti-ThyPeroxAb negative patients achieving remission compared with 39% of anti-ThyPeroxAb positive patients (p = 0.04). Positive ANA and LAC were both highly statistically significantly associated with an increased rate of thrombosis (Table 2). Patients with a positive ANA had a 17% rate of thrombosis compared with 0% in patients with a negative ANA (p = 0.002). Patients with a positive LAC had a 50% rate of thrombosis compared with 11% in patients with a negative LAC (p = 0.001). Conclusions: These results suggest that ITP is a state of immune dysregulation that extends beyond antiplatelet antibodies. Routine measurement of anti-ThyPeroxAb, ANA, and LAC may be helpful in assessing the risk for remission and thrombosis and should be considered for inclusion in future ITP treatment guidelines. Table 1 Table 1. Disclosures Kuter: Genzyme: Consultancy; ONO: Consultancy; GlaxoSmithKline: Consultancy; 3SBios: Consultancy; Shionogi: Consultancy; MedImmune: Consultancy; CRICO: Other: Paid expert testimony; Eisai: Consultancy; Pfizer: Consultancy; Rigel: Consultancy, Research Funding; Syntimmune: Consultancy; Bristol-Myers Squibb: Research Funding; Protalex: Research Funding; Shire: Consultancy; Amgen: Consultancy, Paid expert testimony.
Abstract Background: In CLL/SLL, the iwCLL PR category is heterogeneous and complex to evaluate. Changes in clinical staging (Binet, Rai) have been proposed as a method to evaluate response in CLL (Montserrat, Cancer 1985; iwCLL, Ann Intern Med 1989). Ibrutinib (ibr), a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is indicated by the FDA for the treatment of pts with CLL/SLL and allows for treatment without chemotherapy. Robust improvements in progression-free survival (PFS) and overall survival (OS) among ibr-treated pts in the phase 3 RESONATE trial demonstrated superiority of ibr over ofatumumab (ofa) in heavily pretreated CLL, regardless of prognostic features. As the majority of ibr pts achieved iwCLL PR or PR-L manifested by improved hematologic function and/or disease burden, we analyzed RESONATE pts with PR or PR-L by Binet stage to determine if clinical downstaging captures different, clinically meaningful subgroups among patients in iwCLL PR/PR-L. Methods: Among 391 previously treated CLL pts randomized to receive oral ibr (n=195) or intravenous ofa (n=196), those who achieved a best overall response of PR or PR-L were assessed for Binet Stage at time of first response. Stage A was defined as no anemia or thrombocytopenia and <3/5 sites of involvement (unilateral or bilateral cervical, axillary, and inguinal lymph nodes, liver, spleen); Stage B as no anemia or thrombocytopenia and ≥3/5 involved sites; and Stage C as anemia (hemoglobin <10 g/dL) and/or thrombocytopenia (platelets <100,000/µL) regardless of lymph node/organ site involvement. Binet stage data were considered missing if any one component of the staging criteria was not available. Kaplan-Meier analyses were performed based on Binet Stage at time of first response. Data were analyzed as of the interim analysis (Byrd, N Engl J Med 2014), and p-values are descriptive. Results: A total of 162 (83%) ibr pts and 45 (23%) ofa pts achieved PR/PR-L as best overall response as assessed by investigator; 53% of ibr responders were PR and 46% were PR-L at first response. Baseline characteristics (age, prior therapy, marrow infiltration, unmutated IGHV) were balanced between arms. A majority of PR/PR-L ibr pts were downstaged to Stage A reflecting improvement in lymphadenopathy/organomegaly and/or cytopenias with treatment. At time of first PR/PR-L, the proportion of Stage C pts decreased from 44% (n=72) at baseline to 27% (n=44) for the ibr arm and from 42% (n=19) to 33% (n=15) for the ofa arm. While maintaining PR/PR-L, 48% of ibr-treated and 40% of ofa-treated pts shifted from Stage C to A (or to B/A). The efficacy of ibr over ofa in PR/PR-L pts was similar to that observed in the intent-to-treat population for median PFS (not reached [NR] for ibr vs. 8.48 mo for ofa, P<0.0001). A treatment effect between ibr vs. ofa was also observed for duration of response (DOR) in PR/PR-L pts (NR for ibr vs. 5.52 mo for ofa, P<0.0001). Responders with PR/Stage A showed a longer PFS outcome than responders with PR/Stage C at time of first response to ibr (P=0.0314, Figure). The estimated median PFS for Stage C should be interpreted with caution as it occurred at the tail end of the curve with 2 pts at risk. Within the ofa arm, no difference in PFS between PR/Stage A vs. PR/Stage C was observed, although a limited sample size of responders prohibits robust analysis of this arm. For the ibr arm, both OS (P=0.0281) and DOR (P=0.0431) suggest a trend for improved outcome for PR/Stage A vs. PR/Stage C. Subset analysis (e.g., pts with del17p; PR vs PR-L outcomes) were not feasible because of the small number of pts in these categories. Conclusions: This ad-hoc analysis shows that changes in clinical stage break down the PR/PR-L (iwCLL) category into different, clinically meaningful subgroups, and reinforces the notion that improving cytopenias is a desirable goal of CLL therapy with ibrutinib (Barrientos, ASH 2014). Altogether, this study demonstrates that changes in clinical stage could be a useful and non-costly method to evaluate treatment response at different time points over the course of the disease, a concept with potential clinical implications that requires validation in prospective clinical trials. Disclosures Delgado: Janssen: Consultancy, Honoraria; Novartis/GSK: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Infinity: Research Funding. Suzuki:AbbVie: Equity Ownership; Pharmacyclics, LLC, an Abbie Company: Employment, Other: Leadership, travel, accommodations, expenses. Hsu:AbbVie: Equity Ownership; Pharmacyclics, LLC, an Abbie Company: Employment. James:Pharmacyclics, LLC, an AbbVie Company: Employment; AbbVie: Equity Ownership. Montserrat:Vivia Biotech: Equity Ownership; Pharmacyclics: Consultancy; Janssen: Honoraria, Other: travel, accommodations, expenses; Morphosys: Other: Expert Testimony; Gilead: Consultancy, Other: Expert Testimony.
Introduction Romiplostim is a fusion protein agonist of the thrombopoietin receptor, approved by the US FDA for the treatment of immune thrombocytopenia (ITP) after failure of glucocorticoid therapy. This agent has been examined in other settings, including its use in the management of the thrombocytopenic surgical patient (Marshall et al., Transfusion 2015) and its use for the treatment of refractory aplastic anemia (Gill et al., Br J Haematol 2016). Thrombocytopenia is a complication of chemotherapy in cancer patients that may lead to treatment delays, dose reductions, and discontinuation of therapy (Kuter DJ, Oncology 2015). This study is a retrospective, single-center review of cancer patients who either developed thrombocytopenia as a result of chemotherapy or who had an underlying pre-existing thrombocytopenic disorder (such as ITP or chronic liver disease) who were supported with romiplostim during all or part of their chemotherapy. Methods We performed a retrospective review of patients with solid tumor malignancies who received at least two sequential weekly doses of romiplostim concurrently with chemotherapy. We collected patient demographics, dates and doses of romiplostim administration with corresponding platelet (Plt) counts, and outcomes of therapy, including ability of the treating oncologist to administer chemotherapy before initiating and during use of romiplostim as measured by number of treatment cycles administered, number and duration of delays in therapy, and number and extent of clinically necessary dose reductions. Results Review of pharmaceutical dispensation records from at our institution from January 1, 2010 through April 1, 2016 revealed 19 patients concurrently treated with romiplostim and chemotherapy, with 15 meeting our inclusion criteria (Table 1). At initiation of romiplostim, 40% of patients had a Plt count ≥75 x 109/L and 26.7% of patients had a Plt count ≥100 x 109/L, with a median Plt count of 72 x 109/L (range, 21-145 x 109/L). Patients were treated with weekly injections of romiplostim, with platelet count measured at the time of drug administration; the most common starting dose was 3 mcg/kg. The average duration of romiplostim therapy required to achieve a platelet count ≥75 x 109/L was 13.6 days, and the average time to achieve a platelet count ≥100 x 109/L was 21.1 days. During treatment with romiplostim, 85.3% and 73.2% of all platelet counts measured were ≥75 x 109/L and ≥100 x 109/L, respectively (Figure 1). All patients were able to receive two or more cycles (range, 2-18) of chemotherapy while on romiplostim. Twelve patients (80%) had delays in receiving antineoplastic therapy attributed to thrombocytopenia prior to initiation of romiplostim, with an average per-patient cumulative delay time of 4.7 weeks; 5 patients (33.3%) concurrently treated with romiplostim and chemotherapy had such delays (p=0.010 by Pearson's chi-squared test), with an average per-patient cumulative delay time of 1 week. Eleven patients (73.3%) required at least 1 dose-reduction in chemotherapy attributed to thrombocytopenia prior to initiation of romiplostim; 4 patients (26.7%) required at least 1 such dose-reduction while receiving romiplostim (p=0.011 by Pearson's chi-squared test). Three patients required platelet transfusion and 10 patients required red blood cell (RBC) transfusion while receiving romiplostim, though 8 of the patients received RBC transfusions only for chemotherapy-associated anemia or fatigue. While receiving romiplostim, no patient suffered a thrombotic event, and 3 patients suffered from bleeding (1 patient developed grade 1 mucosal bleeding and 2 patients developed grade 3 gastrointestinal bleeding). Conclusion In patients with solid tumor malignancies with chemotherapy-associated thrombocytopenia or who have co-existing thrombocytopenic disorders (such as ITP or chronic liver disease), this study provides evidence that romiplostim is safe and increases the platelet count sufficiently in a majority of patients to allow subsequent chemotherapy to be given at full dose and on schedule. Table 1 Patient Characteristics. Table 1. Patient Characteristics. Fgure 1 Platelet Count Over Time. The dotted lines represent the platelet count trend of individual patients. The solid black line represents the platelet count trend of the study population (platelet counts averaged together over seven-day intervals). Fgure 1. Platelet Count Over Time. The dotted lines represent the platelet count trend of individual patients. The solid black line represents the platelet count trend of the study population (platelet counts averaged together over seven-day intervals). Disclosures Kuter: Protalex: Research Funding; ONO: Consultancy; Pfizer: Consultancy; 3SBios: Consultancy; Eisai: Consultancy; GlaxoSmithKline: Consultancy; Bristol-Myers Squibb: Research Funding; Genzyme: Consultancy; Shire: Consultancy; Amgen: Consultancy, Paid expert testimony; Shionogi: Consultancy; Rigel: Consultancy, Research Funding; Syntimmune: Consultancy; MedImmune: Consultancy; CRICO: Other: Paid expert testimony.
Abstract Background: Diagnosis of Gaucher disease (GD) can be difficult and diagnostic delays are common in both adult and paediatric patients. This may in part be attributable to the heterogeneous nature of early presenting signs and symptoms in GD, which may result in patients consulting various specialists before a diagnosis is reached. As part of this global Gaucher earlier diagnosis consensus (GED-C) initiative, a panel of expert physicians was asked to determine the most important barriers to diagnosis of GD. The panel was also asked about the impact of the initiative if its primary objective of facilitating earlier diagnosis was realized. Methods: In round 1 of an anonymous, multi-stage, iterative Delphi process, the panel provided free-text answers to a series of open questions, including: "In your experience, what are the greatest barriers to diagnosis in patients with early GD?" and "Assuming that this initiative achieves its goal, what difference could it make to clinical practice?" An independent facilitator grouped the responses to these questions by theme, and these were checked and consolidated as summary statements by the two non-voting co-chairs of the GED-C initiative. In round 2, panel members independently rated the importance of each statement using a 5-point Likert scale (1 = not important, 5 = extremely important). Statements awarded an importance score of at least 3 by more than 75% of respondents were reissued in round 3, in which panel members rated their level of agreement with each statement using a 5-point pivoted Likert scale (1 = strongly disagree; 3 = neither agree nor disagree; 5 = strongly agree). Consensus was defined as more than 67% of respondents agreeing or strongly agreeing (a score of ≥ 4) with a statement. Results: In total, 22 experts from 16 countries were recruited to the GED-C panel. Round 1 (100% response, n = 22) yielded 47 phrases relating to barriers to diagnosis, and 30 relating to the impact of the initiative on clinical practice, which were consolidated as 9 statements describing barriers to diagnosis, and 8 summarizing the initiative's impact. In round 2 (100% response, n = 22) and round 3 (100% response, n = 22), 6 barrier statements and all 8 impact statements met the stipulated importance criteria, and consensus was then reached for all 6 barrier statements and for 7 impact statements (Table). Discussion: This initiative highlights that, as well as the heterogeneous nature of GD, clinicians' lack of awareness of GD and poor knowledge of important presenting signs probably contribute to incorrect or delayed diagnoses. The GED-C initiative aims to resolve this by providing clinicians with simple guidance regarding important factors in GD, thereby improving disease awareness and facilitating early diagnosis. This may improve understanding of the natural history of GD, patient management, and potentially patients' long-term outcomes. Acknowledgment: Submitted on behalf of the GED-C panel members and the European Hematology Association Scientific Working Group 'Quality of Life and Symptoms'. Administration of the GED-C initiative was funded by an unrestricted educational grant from Shire. Table Table. Disclosures Kuter: Bristol-Myers Squibb: Research Funding; ONO: Consultancy; Protalex: Research Funding; Eisai: Consultancy; Shionogi: Consultancy; 3SBios: Consultancy; Syntimmune: Consultancy; MedImmune: Consultancy; CRICO: Other: Paid expert testimony; Amgen: Consultancy, Paid expert testimony; Pfizer: Consultancy; Rigel: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Shire: Consultancy; Genzyme: Consultancy. Salek:Novartis: Research Funding; Bristol-Myers Squibb: Research Funding; Shire: Consultancy; Servier: Consultancy; Sanofi: Research Funding; Agios: Consultancy. Mehta:Protalix/Pfizer: Honoraria, Other: travel grant, Research Funding; Genzyme: Honoraria, Other: travel grant, Research Funding; Actelion: Honoraria, Other: travel grant, Research Funding; Shire: Honoraria, Other: travel grant, Research Funding.
Abstract This article presents a history of the origins and development of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), from the publication of an article titled “A Guide to the Evaluation of Permanent Impairment of the Extremities and Back” (1958) until a compendium of thirteen guides was published in book form in 1971. The most recent, sixth edition, appeared in 2008. Over time, the AMA Guides has been widely used by US states for workers’ compensation and also by the Federal Employees Compensation Act, the Longshore and Harbor Workers’ Compensation Act, as well as by Canadian provinces and other jurisdictions around the world. In the United States, almost twenty states have developed some form of their own impairment rating system, but some have a narrow range and scope and advise evaluators to consult the AMA Guides for a final determination of permanent disability. An evaluator's impairment evaluation report should clearly document the rater's review of prior medical and treatment records, clinical evaluation, analysis of the findings, and a discussion of how the final impairment rating was calculated. The resulting report is the rating physician's expert testimony to help adjudicate the claim. A table shows the edition of the AMA Guides used in each state and the enabling statute/code, with comments.
Abstract Physicians who use the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) often serve as medical expert witnesses. In workers’ compensation cases, the expert may appear in front of a judge or hearing officer; in personal injury and other cases, the physician may testify by deposition or in court before a judge with or without a jury. This article discusses why medical expert witnesses are needed, what they do, and how they can help or hurt a case. Whether it is rendered by a judge or jury, the final opinions rely on laypersons’ understanding of medical issues. Medical expert testimony extracts from the intricacies of the medical literature those facts the trier of fact needs to understand; highlights the medical facts pertinent to decision making; and explains both these in terms that are understandable to a layperson, thereby enabling the judge or jury to render well-informed opinions. For expert witnesses, communication is everything, including nonverbal communication that critically determines if judges and, particularly, jurors believe a witness. To these ends, an expert medical witnesses should know the case; be objective; be a good teacher; state opinions clearly; testify with appropriate professional demeanor; communicate well, both verbally and nonverbally; in verbal communications, explain medical terms and procedures so listeners can understand the case; and avoid medical jargon, finding fault or blaming, becoming argumentative, or appearing arrogant.
