Parkinson’s Patients’ Tolerance for Risk and Willingness to Wait for Potential Benefits of Novel Neurostimulation Devices: A Patient-Centered Threshold Technique Study

Background. Parkinson’s disease (PD) is neurodegenerative, causing motor, cognitive, psychological, somatic, and autonomic symptoms. Understanding PD patients’ preferences for novel neurostimulation devices may help ensure that devices are delivered in a timely manner with the appropriate level of evidence. Our objective was to elicit preferences and willingness-to-wait for novel neurostimulation devices among PD patients to inform a model of optimal trial design. Methods. We developed and administered a survey to PD patients to quantify the maximum levels of risks that patients would accept to achieve potential benefits of a neurostimulation device. Threshold technique was used to quantify patients’ risk thresholds for new or worsening depression or anxiety, brain bleed, or death in exchange for improvements in “on-time,” motor symptoms, pain, cognition, and pill burden. The survey elicited patients’ willingness to wait to receive treatment benefit. Patients were recruited through Fox Insight, an online PD observational study. Results. A total of 2740 patients were included and a majority were White (94.6%) and had a 4-year college degree (69.8%). Risk thresholds increased as benefits increased. Threshold for depression or anxiety was substantially higher than threshold for brain bleed or death. Patient age, ambulation, and prior neurostimulation experience influenced risk tolerance. Patients were willing to wait an average of 4 to 13 years for devices that provide different levels of benefit. Conclusions. PD patients are willing to accept substantial risks to improve symptoms. Preferences are heterogeneous and depend on treatment benefit and patient characteristics. The results of this study may be useful in informing review of device applications and other regulatory decisions and will be input into a model of optimal trial design for neurostimulation devices.

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Contrasting evidence to reimbursement reality for off-label use (OLU) of drug treatments in cancer care: rationale and design of the CEIT-OLU project

ESMO Open ◽

10.1136/esmoopen-2019-000596 ◽

2019 ◽

Vol 4 (6) ◽

pp. e000596

Author(s):

Amanda Katherina Herbrand ◽

Andreas Michael Schmitt ◽

Matthias Briel ◽

Stefan Diem ◽

Hannah Ewald ◽

...

Keyword(s):

Cancer Care ◽

Clinical Evidence ◽

Patient Characteristics ◽

Evidence Based ◽

Cancer Drugs ◽

Off Label Use ◽

Level Of Evidence ◽

Treatment Benefit ◽

Off Label ◽

Label Use

BackgroundOff-label use (OLU) of a drug reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many healthcare systems. OLU is frequently regulated by reimbursement restrictions. For evidence-based healthcare, treatment ought to be reimbursed if there is sufficient clinical evidence for treatment benefit independently of patient factors not related to the treatment indication. However, little is known about the reality of OLU reimbursement and its association with the underlying clinical evidence. Here, we aim to investigate the relationship of reimbursement decisions with the underlying clinical evidence.Methods/ designWe will extract patient characteristics and details on treatment and reimbursement of cancer drugs from over 3000 patients treated in three Swiss hospitals. We will systematically search for clinical trial evidence on benefits associated with OLU in the most common indications. We will describe the prevalence of OLU in Switzerland and its reimbursement in cancer care, and use multivariable logistic regression techniques to investigate the association of approval/rejection of a reimbursement requests to the evidence on treatment effects and to further factors, including type of drug, molecular predictive markers and the health insurer.DiscussionOur study will provide a systematic overview and assessment of OLU and its reimbursement reality in Switzerland. We may provide a better understanding of the access to cancer care that is regulated by health insurers and we hope to identify factors that determine the level of evidence-based cancer care in a highly diverse western healthcare system.

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Contrasting Evidence to Reimbursement Reality for Off-label use (OLU) of Drug Treatments in Cancer Care – Rationale and Design of the CEIT-OLU-project

10.1101/19003152 ◽

2019 ◽

Author(s):

AK Herbrand ◽

AM Schmitt ◽

M Briel ◽

S Diem ◽

H Ewald ◽

...

Keyword(s):

Health Care ◽

Cancer Care ◽

Clinical Evidence ◽

Health Care Systems ◽

Patient Characteristics ◽

Evidence Based ◽

Cancer Drugs ◽

Level Of Evidence ◽

Treatment Benefit ◽

Off Label

AbstractBackgroundOff-label drug use (OLU) reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many health care systems. OLU is frequently regulated by reimbursement restrictions. For evidence-based health care, treatment ought to be reimbursed if there is sufficient clinical evidence for treatment benefit independently of patient factors not related to the treatment indication. However, little is known about the reality of OLU reimbursement and its association with the underlying clinical evidence. Here we aim to investigate the relationship of reimbursement decisions with the underlying clinical evidence.Methods/DesignWe extract patient characteristics and details on treatment and reimbursement of cancer drugs from over 3000 patients treated in three Swiss hospitals. We systematically search for clinical trial evidence on benefits associated with OLU in the most common indications. We will describe the prevalence of OLU in Switzerland and its reimbursement in cancer care, and use multivariable logistic regression techniques to investigate the association of approval/rejection of a reimbursement requests to the evidence on treatment effects and to further factors, including type of drug, molecular predictive markers and the health insurer.DiscussionOur study will provide a systematic overview and assessment of OLU and its reimbursement reality in Switzerland. We may provide a better understanding of the access to cancer care that is regulated by health insurers and we hope to identify factors that determine the level of evidence-based cancer care in a highly diverse Western health care system.

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Reproductive Performance Following Hysteroscopic Surgery for Uterine Septum: Results from a Single Surgeon Data

Journal of Clinical Medicine ◽

10.3390/jcm10010130 ◽

2021 ◽

Vol 10 (1) ◽

pp. 130

Author(s):

Ertan Saridogan ◽

Mona Salman ◽

Lerzan Sinem Direk ◽

Ali Alchami

Keyword(s):

Reproductive Performance ◽

Observational Studies ◽

Patient Characteristics ◽

Reproductive Outcomes ◽

Hysteroscopic Surgery ◽

High Quality Evidence ◽

Study Results ◽

Significant Difference ◽

Uterine Septum

Uterine septum can negatively affect reproductive outcomes in women. Based on evidence from retrospective observational studies, hysteroscopic incision has been considered a solution to improve reproductive performance, however there has been recent controversy on the need for surgery for uterine septum. High quality evidence from prospective studies is still lacking, and until it is available, experts are encouraged to publish their data. We are therefore presenting our data that involves analysis of the patient characteristics, surgical approach and long-term reproductive outcomes of women who received treatment for uterine septum under the care of a single surgeon. This includes all women (99) who underwent hysteroscopic surgery for uterine septum between January 2001 and December 2019. Of those 99 women treated for intrauterine septum who were trying to conceive, 91.4% (64/70) achieved pregnancy, 78.6% (55/70) had live births and 8.6% (6/70) had miscarriages. No statistically significant difference was found in the live birth rates when data was analyzed in subgroups based on age, reason for referral/aetiology and severity of pathology. Our study results support the view that surgical treatment of uterine septa is beneficial in improving reproductive outcomes.

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Composite Breast Remodeling After Implant Removal by Tissue Recruitment and Loops Fixation With Power-Assisted Liposuction and Lipofilling (PALLL)

Aesthetic Surgery Journal ◽

10.1093/asj/sjaa327 ◽

2021 ◽

Author(s):

Marwan H Abboud ◽

Ayush K Kapila ◽

Svetlana Bogaert ◽

Nicolas M Abboud

Keyword(s):

Breast Implant ◽

Capsular Contracture ◽

Patient Characteristics ◽

Fat Grafting ◽

Implant Removal ◽

Level Of Evidence ◽

Patient Reported ◽

Aesthetic Results ◽

And Migration ◽

The Aesthetic

Abstract Background An increasing number of women wish breast implant removal whilst maintaining an acceptable projection and form were possible. Objectives The authors propose a technique to remodel the breast after implant removal utilizing internal suture loops to project the breast, recruit abdominal and axillary tissue cranially and medially, and provide a matrix for lipofilling. Methods A prospective analysis was performed of consecutive patients undergoing implant extraction followed by power-assisted liposuction loops and lipofilling. Patient characteristics were measured. The aesthetic results were evaluated by 2 independent raters. Patient-reported satisfaction was measured by standardized questionnaires. Results Implants in 52 patients with an average age of 55 and body mass index of 23.7 were extracted followed by breast remodeling. A total of 73% of patients had implants for aesthetic reasons, 41% were smokers, and 43% of the reconstruction cases received radiotherapy. A total of 28% had implant extraction for rupture, 58% for capsular contracture, and 14% due to pain and migration. The average volume of the implants removed was 292 cc, followed by an average lipofilling of 223 cc, yielding a ratio of 0.76 to 1. The average tissue recruited by loops was 82.5 cc. Independent raters measured 79% of results as good, 13% as acceptable, and 8% as requiring improvement; 80% of patients were satisfied to very satisfied. Conclusions The authors propose implant extraction followed by power-assisted liposuction loops and lipofilling can provide footprint definition, sustained projection, and high patient satisfaction. Moreover, the recruitment of a vascularized adipo-cutaneous flap by loops allows a reduced ratio of fat grafting to implant volume. Level of Evidence: 4

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Survey to describe variability in early onset scoliosis cast practices

Journal of Children s Orthopaedics ◽

10.1302/1863-2548.12.170207 ◽

2018 ◽

Vol 12 (4) ◽

pp. 406-412 ◽

Cited By ~ 2

Author(s):

A. Grzywna ◽

A. McClung ◽

J. Sanders ◽

P. Sturm ◽

L. Karlin ◽

...

Keyword(s):

Early Onset ◽

Congenital Scoliosis ◽

Patient Characteristics ◽

Study Groups ◽

Early Onset Scoliosis ◽

Radiographic Evaluation ◽

Level Of Evidence ◽

Major Curve ◽

Radiographic Measurements ◽

Multicentre Research

Purpose To investigate paediatric orthopaedists’ cast practices for early onset scoliosis regarding patient selection, cast application, radiographic evaluation, treatment cessation and adjunctive bracing. Methods A casting survey was distributed to all paediatric orthopaedists in Children’s Spine and Growing Spine Study Groups (n = 92). Questions included physician and patient characteristics, technique, treatment, outcomes, radiographic measurements and comparison to other treatments. A total of 55 orthopaedists (60%) responded, and descriptive statistics were calculated on the subset who cast (n = 45). Results A majority of respondents use cast treatment for idiopathic and syndromic scoliosis patients, but not for neuromuscular or congenital scoliosis patients. Major curve angle ranked most important in orthopaedists’ decision to commence cast treatment, in comparison with rib-vertebra angle difference or clinical observations. The major curve angle threshold to initiate casting was a median of 30° (20° to 70°), and the minimum patient age was median ten months (3 to 24). First in-cast and out-of-cast radiographs are taken standing, supine, awake, under anesthesia and/or in traction. In all, 58% consistently cast over or under the arm, while 44% vary position by patient. Respondents were divided about the use of a brace after cast treatment: 22% do not prescribe a brace, 31% always do and 36% do in some patients. Conclusions Future multicentre research studies must standardize radiographic practices and consider age and major curve angle at cast initiation and termination, scoliosis aetiology, shoulder position and treatment duration. Practices need to be aligned or compared in these areas in order to distinguish what makes for the best cast treatment possible. Level of Evidence V, Expert opinion

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Acetabular Chondral Lesions in Hip Arthroscopy: Relationships Between Grade, Topography, and Demographics

The American Journal of Sports Medicine ◽

10.1177/0363546517708192 ◽

2017 ◽

Vol 45 (11) ◽

pp. 2501-2506 ◽

Cited By ~ 18

Author(s):

Carlos Suarez-Ahedo ◽

Chengcheng Gui ◽

Stephanie M. Rabe ◽

Sivashankar Chandrasekaran ◽

Parth Lodhia ◽

...

Keyword(s):

Traumatic Injury ◽

Demographic Factors ◽

Patient Characteristics ◽

Cross Sectional Study ◽

Chondral Lesion ◽

Level Of Evidence ◽

Cross Sectional ◽

Chondral Lesions ◽

Chondral Damage ◽

Male Sex

Background: Hip pain remains a challenge given the multiple factors that can cause damage to the articular cartilage, such as traumatic injury, metabolic damage, and morphologic variations such as femoroacetabular impingement (FAI) and that can contribute to progression of osteoarthritis. However, a direct relationship between patient characteristics, the extent of acetabular chondral damage, and topologic characteristics of chondral lesions has not been established. Purpose: To compare the grade of acetabular chondral damage, measured in terms of acetabular labrum articular disruption (ALAD) classification, to the size and position of the chondral lesions, matching patients’ demographic factors such as age and body mass index (BMI). Study Design: Cross-sectional study; Level of evidence, 3. Methods: This study included all hip arthroscopies performed by the corresponding author from August 7, 2008, to November 19, 2014, in which acetabular chondral lesions were intraoperatively identified and measured in terms of ALAD grade, clockface location, and size. Bivariate analyses and multiple logistic regression were used to identify the demographic factors, characteristics of the acetabular chondral lesion, and other anatomic characteristics that were related to the ALAD grade of the acetabular chondral lesion. Results: Acetabular chondral lesions were measured in 1502 patients during the study period. Multivariate analysis showed that higher ALAD grade of acetabular chondral damage was significantly related to male sex, more advanced age, the area of the acetabular chondral lesion, anterior extension of the acetabular chondral lesion within the anterosuperior quadrant, labral detachment from the acetabular cartilage, and posterior extension of the labral tear. Conclusion: Higher grades of acetabular chondral damage were related to male sex, increased age, height, weight, BMI, and the size of the lesion. Chondral lesions were generally found in the anterosuperior region of the acetabulum, consistent with labral lesions and the weightbearing area of the acetabulum.

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PP205 The Use Of Real-World Evidence To Support National Institute For Health And Care Excellence Medical Technology Submissions

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462321001306 ◽

2021 ◽

Vol 37 (S1) ◽

pp. 26-26

Author(s):

Scott Gibson ◽

Sita Saunders ◽

Maximilian Blüher ◽

Amanda Hansson Hedblom ◽

Rafael Torrejon Torres ◽

...

Keyword(s):

Decision Making ◽

Real World ◽

Trial Design ◽

Clinical Evidence ◽

Patient Characteristics ◽

The United Kingdom ◽

Real World Evidence ◽

Guidance Documents ◽

Meta Analyses ◽

Positive Recommendation

IntroductionAlthough randomized controlled trials (RCTs) are recognized as providing the highest level of clinical evidence, few medical device RCTs are available due to underfunding or inherent challenges associated with trial design. This study examines the extent to which real-world evidence (RWE) supports the recommendations made by the National Institute for Health and Care Excellence Medical Technologies Evaluation Programme (MTEP).MethodsAll MTEP guidance documents published online prior to October 2020 were reviewed. The “case for adoption” recommendation, type of clinical data, and clinical critiques for each MTEP submission were extracted and categorized. RWE was defined as studies with neither blinding nor prospective selection or control of patient characteristics.ResultsOf the MTEP submissions reviewed, 34 of 45 (76%) received a positive recommendation. Independent of outcome, all submissions included RWE, but only 19 (42%) utilized RCT evidence (15 were recommended and four were not). Meta-analyses of RWE were used whenever possible. The most common clinical critiques in unsuccessful submissions were the following: (i) not generalizable to the United Kingdom National Health Service (NHS); (ii) low quality; (iii) likelihood of bias; (iv) trial design faults; (v) uncertain benefit; and (vi) evidence unrelated to scope.ConclusionsThis study suggests that while the use of RCTs has not always led to a positive recommendation, RWE can be valuable in decision-making. Evidence that is generalizable to the NHS, is related to the scope, and shows clear indication of benefit is more likely to positively influence MTEP decision-making.

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The Prostate Cancer Prevention Trial: Design, Biases and Interpretation of Study Results

The Journal of Urology ◽

10.1016/s0022-5347(06)00284-9 ◽

2006 ◽

Vol 175 (6) ◽

pp. 2234-2242 ◽

Cited By ~ 28

Author(s):

Phyllis J. Goodman ◽

Ian M. Thompson ◽

Catherine M. Tangen ◽

John J. Crowley ◽

Leslie G. Ford ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Prevention ◽

Trial Design ◽

Prevention Trial ◽

Prostate Cancer Prevention ◽

Study Results ◽

Prostate Cancer Prevention Trial

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Abstract 129: Endovascular Thrombectomy Potential Benefits in Isolated M2 Occlusions Are Related to Stroke Severity and Penumbral Mismatch Deficit: A Secondary Analysis From the SELECT Study

Stroke ◽

10.1161/str.51.suppl_1.129 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Amrou Sarraj ◽

Ameer Hassan ◽

James C Grotta ◽

Clark Sitton ◽

Spiros Blackburn ◽

...

Keyword(s):

Infarct Volume ◽

Secondary Analysis ◽

Lesion Size ◽

Stroke Severity ◽

Perfusion Deficit ◽

Multicenter Cohort Study ◽

Treatment Benefit ◽

Endovascular Thrombectomy ◽

Excellent Outcome ◽

Potential Benefits

Background: The efficacy of endovascular thrombectomy (EVT) in M2 occlusions is uncertain. Methods: In a prospective multicenter cohort study of imaging selection (SELECT), EVT outcomes were compared to medical managment (MM) in M2 occlusions. Further, we assessed for potential treatment benefit in patients with higher stroke severity (NIHSS) and a larger perfusion deficit on CTP (Tmax > 6 sec - ischemic core volume)The primary outcome was excellent outcome (mRS 0-1). Results: of 361 patients enrolled in SELECT, 87 had isolated M2 occlusion (EVT 59, MM 28). Baseline NIHSS median (IQR) (EVT 14 (10-20), MM 15 (9.5-19.5), p=0.72) and infarct volume rCBF<30% (EVT 7 (0-21) vs MM 18.5 (0-41.25), P=0.10). EVT was associated with higher rates of excellent outcomes (53% vs 21%, aOR:6.94, 95% CI=1.86-25.90, p=0.004) with a shift towards better mRS outcomes (adj cOR: 3.49, 95% CI=1.39-8.80, p=0.008), smaller final infarct volume (15.9 (2.7-48.0) vs 58 (24.3-141.9), P<0.001), and a reduction of neurological worsening (3% vs 22%, p=0.011), sICH (2% vs 21%, p=0.004), and mortality (5% vs 25%, p=0.011). Assessing outcomes in NIHSS strata; there was no significant increase in excellent outcomes rates in NIHSS ≤10 (EVT 65% vs MM 50%, aOR=1.59, 95% CI=0.21-12.01, p=0.65). In contrast, patients with NIHSS>10 had better outcomes with EVT (46%) vs MM (10%), aOR=11.39, 95% CI=1.80-72.11, p=0.01 as shown in figure 1. As perfusion deficit lesion size increased, the odds of achieving excellent outcomes was reduced (for each 10cc by 11%, aOR: 0.89, 95% CI=0.79-1.00, p=0.05). Excellent outcomes declined in patients with MM as perfusion deficit lesion size increased, yet in the EVT they were maintained as shown in figure 2. Similar results were obtained for mRS 0-2. Conclusion: EVT may result in better rates of excellent outcomes in isolated M2 occlusions, especially those with more severe strokes and larger perfusion deficits who are more likely to have worse outcomes without emergent reperfusion.

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Effect of spin in the abstract of a randomised controlled trial on physiotherapists’ perception of treatment benefit: a randomised controlled trial

BMJ evidence-based medicine ◽

10.1136/bmjebm-2021-111714 ◽

2021 ◽

pp. bmjebm-2021-111714

Author(s):

Heppy Khanpara ◽

V Prakash

Keyword(s):

Randomised Controlled Trial ◽

Beneficial Effect ◽

Controlled Trial ◽

Experimental Treatment ◽

Medium Effect ◽

Clinical Settings ◽

Treatment Benefit ◽

Experimental Intervention ◽

Study Results ◽

Randomised Controlled

ObjectiveTo assess the effect of spin in the abstract of a randomised controlled trial (RCT) on physiotherapists’ perception of treatment benefit evaluated in the trial.DesignParallel-group RCT.SettingPhysiotherapy departments in hospitals and clinics in India.ParticipantsPhysiotherapists working in clinical settings.InterventionsWe selected one abstract with high level of spin published in one of the core journals of physiotherapy and created two versions of the abstract, that is, with and without spin. We randomly assigned physiotherapists working in clinical settings (N=128) to read one version of the selected abstract, with or without spin. Participants were blinded to the study design, objectives and randomisation.Main outcome measuresPhysiotherapists’ interpretation of beneficial effect of the experimental treatment (0–10 scale) reported in the abstract. The secondary outcomes were clinicians’ perception of methodological rigour and the study importance, their interest in reading the full text, and their interest in running another trial evaluating this treatment.ResultsWe found a medium reduction in confidence of beneficial effect of the experimental treatment among physiotherapists who read the abstract without spin (mean score 4.3±2.8) compared with those who read the abstract with spin (mean score 6.14±2.6). The mean difference in scores between abstracts with and without spin was 1.8 (95% CI 0.8 to 2.8; p<0.001). For other outcomes measures studied there was no statistically significant effect.ConclusionsRemoval of spin in the abstract of RCT reporting statistically non-significant results have medium effect in improving physiotherapists’ accuracy of interpretation of study results. Spin contributes to clinicians’ positive perception about the benefit of experimental intervention tested in the trial despite the evidence showing no superiority of experimental intervention.Trial registration numberCTRI/2020/02/023557.

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