The “Efficacy-Effectiveness Gap”: Historical Background and Current Conceptualization

Nordon, Clémentine; Karcher, Hélène; Groenwold, Rolf H.H.; Ankarfeldt, Mikkel Zöllner; Pichler, Franz; Chevrou‐Séverac, Hélène; Rossignol, Michel; Abbé, Adeline; Abenhaim, Lucien

doi:10.1016/j.jval.2015.09.2938

Cited by 124 publications

(103 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Approved since 2006 in the United States to treat myelodysplastic syndrome and since 2012 in the European Union with an indication for treatment of adult AML patients who are not candidates for standard induction chemotherapy, it showed improved response rates as compared with standard available therapies and no major safety issues in clinical trials conducted in elderly AML patients . Real‐world (RW) studies are needed to confirm and support clinical studies results in unselected and heterogenous populations of routinely treated patients, in order to translate clinical trials into clinical practice (so called efficacy‐effectiveness gap) . Despite widespread use of decitabine to treat AML, RW data based on the registered treatment schedule (20 mg/m 2 daily for 5 days) are very scanty .…”

Section: Introductionmentioning

confidence: 99%

Real‐world experience with decitabine as a first‐line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy

Bocchia

Candoni²,

Borlenghi

et al. 2019

Hematological Oncology

View full text Add to dashboard Cite

Despite widespread use of decitabine to treat acute myeloid leukaemia (AML), data on its effectiveness and safety in the real‐world setting are scanty. Thus, to analyze the performance of decitabine in clinical practice, we pooled together patient‐level data of three multicentric observational studies conducted since 2013 throughout Italy, including 306 elderly AML patients (median age 75 years), unfit for intensive chemotherapy, treated with first‐line decitabine therapy at the registered schedule of 20 mg/m2/iv daily for 5 days every 4 weeks. Overall response rate (ORR), overall survival (OS) curves, and multivariate hazard ratios (HRs) of all‐cause mortality were computed. Overall, 1940 cycles of therapy were administered (median, 5 cycles/patient). A total of 148 subjects were responders and, therefore, ORR was 48.4%. Seventy‐one patients (23.2%) had complete remission, 32 (10.5%) had partial remission, and 45 (14.7%) had haematologic improvement. Median OS was 11.6 months for patients with favourable‐intermediate cytogenetic risk and 7.9 months for those with adverse cytogenetic risk. Median relapse‐free survival after CR was 10.9 months (95% confidence interval [CI]: 8.7‐16.0). In multivariate analysis, mortality was higher in patients with adverse cytogenetic risk (HR=1.58; 95% CI: 1.13‐2.21) and increased continuously with white blood cell (WBC) count (HR=1.12; 95% CI: 1.06‐1.18). A total of 183 infectious adverse events occurred in 136 patients mainly (>90%) within the first five cycles of therapy. This pooled analysis of clinical care studies confirmed, outside of clinical trials, the effectiveness of decitabine as first‐line therapy for AML in elderly patients unfit for intensive chemotherapy. An adverse cytogenetic profile and a higher WBC count at diagnosis were, in this real life setting, unfavourable predictors of survival.

show abstract

Section: Introductionmentioning

confidence: 99%

Real‐world experience with decitabine as a first‐line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy

Bocchia

Candoni²,

Borlenghi

et al. 2019

Hematological Oncology

View full text Add to dashboard Cite

show abstract

“…The focus on HRs from clinical trials is further complicated by the 'efficacy-effectiveness gap', the commonly observed discrepancy between clinical trial results and the performance of a treatment in real-world practice [10]. For welldocumented reasons -including healthcare system characteristics, clinical trial measurement methods and complex interactions between a drug's biological effect and contextual factors -clinical trials do not always predict realworld outcomes [11]. Results obtained in formal trials can over-or underestimate real-world effectiveness.…”

Section: Discussionmentioning

confidence: 99%

Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators

Paddock¹,

Goodman

Shortenhaus

et al. 2017

Future Oncol.

View full text Add to dashboard Cite

Aim: Several recently developed frameworks aim to assess the value of cancer treatments, but the most appropriate metrics remain uncertain. Methods: We use data from the Patient Access to Cancer care Excellence Continuous Innovation Indicators to examine the relationship between hazard ratios (HRs) from clinical trials and dynamic therapeutic value accumulating over time. Results: Our analysis shows that HRs from initial clinical trials poorly predict the eventual therapeutic value of cancer treatments. Conclusion: Relying strongly on HRs from registration trials to predict the long-term success of treatments leaves a lot of the variance unexplained. The Continuous Innovation Indicators offer a complementing, dynamic method to track the therapeutic value of cancer treatments and continuously update value assessments as additional evidence accumulates. Concerns about increased healthcare costs and the ability to pay for meaningful health improvements have fueled discussions about value in healthcare. Various organizations have responded by developing value frameworks to assess the relative benefits of therapeutic interventions. These frameworks typically assess new treatments at the time of launch based on data from initial registration trials and other available information. Some of these frameworks rely mainly on hazard ratios (HRs) of primary end points from registration trials, because these measures often provide the only available estimate of efficacy. However, the extent to which HRs from initial trials predict future value of new therapies is unclear. Moreover, while current value frameworks provide a good initial basis for conceptualizing value, they are not designed to consider value across the lifecycle of a treatment, and they inadequately account for patient preferences.Several examples of published case studies attempt to quantify value dynamically. Among these is the application of Garrison and Veenstra's dynamic lifecycle model to trastuzumab to calculate annual incremental cost-effectiveness ratios (ICERs) for two indications: metastatic breast cancer and adjuvant treatment for early breast cancer [1]. That model demonstrated a decrease over time in ICERs for the combined indications. Similarly, Lu et al. conducted an analysis of the dynamic cost-effectiveness of docetaxel and paclitaxel as new indications arose and patents expired [2]. They concluded, "One direction for future research might be to create a predictive tool that estimates the predicted long-term dynamic ICER for a specific drug at product launch. … All these sources of information can be used together to predict the probability of different events over a drug's life cycle." KEYWORDShazard ratio • health economics • value assessment

show abstract

“…Efficacy trials determine whether an intervention produces the expected result under ideal circumstances. Effectiveness trials measure the degree of beneficial effect under real world clinical settings . For these lifestyle modifications in hypertension, efficacy has been well established, but effectiveness less so.…”

Section: Efficacy Vs Effectivenessmentioning

confidence: 99%

“…Similarly, for exercise, the interventions are of a supervised exercise program and not an exhortation to “do more exercise.” Last, the data on alcohol reduction is also based on successful reduction with intensive counseling and follow up. All of the 3 aspects in the first paradigm of the efficacy to effectiveness gap apply here: physician behavior, attention to adherence, and disparity in access to resources and care . Clearly interventions as described above are thus not feasible to be translated into routine clinical practice yet, and hence, it is unreasonable to expect a remarkable behavior change from mere counselling.…”

Section: Efficacy Vs Effectivenessmentioning

confidence: 99%

Towards better blood pressure: Do non‐pharmacological strategies provide the right path?

Hiremath

2018

J of Clinical Hypertension

View full text Add to dashboard Cite

A scene like this plays out many times every day: A patient with newly diagnosed hypertension, confirmed with out-of-office readings, is seen in the clinic. What happens next depends on the patient, the doctor, and other less understood dynamics of that interaction. In most settings, the patient walks out with a plan to change their lifestyle, a prescription for a pill, or sometimes both. On one hand, most individuals demonstrate significant pill disutility, defined as the longevity gain desired by an individual to offset the inconvenience of taking a preventative tablet for life.1 This can vary considerably, ranging from >1 month for about twothirds of patients, to 12% demonstrating extreme pill disutility (bordering on pill hatred), 2 actually desiring ≥10 year increased life expectancy before taking any new medication. 1 On the other hand, undoubtedly, giving a prescription for a medication is a much faster and easier option for the physician. Data from a large health maintenance organization, which has achieved an enviable 85% hypertension control, demonstrate that the path to lower blood pressure does go through optimal pharmacotherapy. 3 Additionally, a successful non-pharmacological strategy should take into account the patient motivation for lifestyle changes and the pieces needed for actual execution, not just counselling for eating less salt. The paper by Liu et al tackle the latter aspect, using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 survey of the 4000 hypertensive patients who reported that a recommendation from their doctor for any 1 (or more) of 4 non-pharmacologic strategies (less sodium, less alcohol, more physical activity, or weight loss). 4 As expected, reducing sodium intake was the most common (68%) and alcohol reduction the most uncommon (26%)recommendation. The self-reported adoption rates of these strategies were very high (ranging from 59% to 87%), but despite this, almost half the patients (47%) still had uncontrolled hypertension.

show abstract

The “Efficacy-Effectiveness Gap”: Historical Background and Current Conceptualization

Cited by 124 publications

References 53 publications

Real‐world experience with decitabine as a first‐line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy

Real‐world experience with decitabine as a first‐line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy

Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators

Towards better blood pressure: Do non‐pharmacological strategies provide the right path?

Contact Info

Product

Resources

About