Claims-based Algorithm for Amyloidosis

Overseen By Cinthia S De Freitas, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Disqualifiers: Opted out of research, Pregnancy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a computer algorithm designed to identify individuals with ATTR amyloidosis, a condition where abnormal protein accumulates in organs such as the heart and nerves. The goal is to determine if the algorithm can accurately detect those who might have the disease. This study may suit patients at Yale flagged by the algorithm as potentially having ATTR and receiving care through Yale's health system. Researchers will contact participants for further evaluation to confirm the diagnosis. As an Early Phase 1 trial, this research focuses on understanding the algorithm's effectiveness in identifying the disease, offering participants a chance to contribute to groundbreaking diagnostic advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this algorithm is safe for diagnosing ATTR amyloidosis?

Research has shown that diagnostic tools for ATTR, a heart condition caused by abnormal protein deposits, are generally safe for patients. In studies on ATTR cardiac amyloidosis, treatments like VYNDAQEL® exhibited side effects similar to those of a placebo (a harmless pill used for comparison). This indicates that diagnosing ATTR with these tools does not raise major safety concerns. Although other treatments for ATTR might have side effects, the diagnostic tools themselves are well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses a claims-based algorithm to diagnose ATTR Amyloidosis, which is a fresh approach compared to the usual diagnostic methods like biopsy and imaging. This algorithm has the potential to streamline the identification process by analyzing existing health claims data, offering a non-invasive and quicker alternative. By leveraging big data, this method could allow for earlier detection and treatment, ultimately improving patient outcomes.

What evidence suggests that this algorithm is effective for diagnosing ATTR amyloidosis?

Research on diagnosing ATTR amyloidosis has shown various effective identification methods. Current techniques often combine tests, such as imaging scans and specific heart assessments, to detect the disease. In this trial, a computer algorithm will evaluate participants by identifying ATTR amyloidosis through claims-based data. This new approach aims to enhance early detection by utilizing medical claims data, potentially identifying patients sooner. Early diagnosis is crucial, as patients diagnosed earlier with ATTR amyloidosis often experience better health outcomes. Although direct data on the effectiveness of this new method is not yet available, its goal is to simplify the diagnosis process and enable early disease detection. ^{1 3 6 7 8}

Who Is on the Research Team?

Edward Miller, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for patients within the YNHHS claims dataset who are flagged by a computer algorithm as potentially having ATTR amyloidosis, which includes both hereditary and non-hereditary forms. They must be willing to undergo further clinical evaluation. Pregnant individuals or those opting out of research in the Epic system cannot participate.

Inclusion Criteria

I have been identified as having ATTR amyloidosis by a specific diagnostic algorithm.

I need further tests to confirm if I have ATTR amyloidosis.

I am at risk for ATTR and am being treated within the YNHHS system.

Exclusion Criteria

Patients who are pregnant or who may become pregnant

I have not opted out of research in the Epic system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Evaluation

Participants are evaluated for the identification of ATTR Amyloidosis through a claims-based algorithm

2 years

Follow-up

Participants are monitored for safety and effectiveness after evaluation

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ATTR diagnostic algorithm

Trial Overview The study is testing the effectiveness of a computer algorithm designed to identify patients at risk of ATTR amyloidosis using medical records data. The goal is to see how well this algorithm predicts actual cases when compared with Yale's list of potential subjects.

How Is the Trial Designed?

Group I: Computer algorithm for ATTR Experimental Treatment 1 Intervention

Patients will be evaluated for the identification of ATTR Amyloidosis through a claims-based algorithm

ATTR diagnostic algorithm is already approved in United States for the following indications:

Approved in United States as Vyndaqel / Vyndamax for:

• Transthyretin amyloidosis cardiomyopathy (ATTR-CM)

Approved in United States as Attruby for:

• Transthyretin amyloidosis (ATTR) with heart involvement (cardiomyopathy)

Approved in United States as diflunisal for:

• Hereditary ATTR amyloidosis

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Alnylam Pharmaceuticals Inc

Collaborator

Trials

1

Recruited

100+

Published Research Related to This Trial

The study evaluated algorithms for identifying rheumatoid arthritis (RA) in claims data, finding that the ICD-10 codes M05 and M06 have high positive predictive values (PPVs) of 81%, making them reliable for RA identification in a large German health insurance database.

Using additional criteria such as inflammatory markers, rheumatologist visits, or specific medications improved the accuracy of RA identification, with specific medication showing the highest discriminative properties (diagnostic odds ratio of 3.0).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of rheumatoid arthritis in German claims data using different algorithms: Validation by cross-sectional patient-reported survey data. Callhoff, J., Albrecht, K., Marschall, U., et al.[2023]

In a long-term study of 40 Japanese patients with hereditary ATTR amyloidosis, diflunisal was found to be well-tolerated, with most patients experiencing sustained clinical benefits over an average of 38 months, although some experienced renal function deterioration and thrombocytopenia.

Diflunisal significantly increased serum TTR concentration and stabilized the TTR tetramer structure, with no deterioration in neurological and cardiac functions observed after 24 months of treatment, indicating its efficacy in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of long-term diflunisal administration in hereditary transthyretin (ATTR) amyloidosis. Sekijima, Y., Tojo, K., Morita, H., et al.[2015]

In a study of 23 patients with transthyretin amyloid cardiomyopathy (ATTR-CA), diflunisal was found to be well-tolerated, with only 13% of patients withdrawing due to gastrointestinal side effects, indicating its potential safety in this population.

The treatment did not lead to significant adverse events, such as clinically significant bleeding or hospitalizations for heart failure, suggesting that diflunisal can be safely administered with proper monitoring in patients with both hereditary and wild-type ATTR-CA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diflunisal tolerability in transthyretin cardiac amyloidosis: a single center's experience. Ikram, A., Donnelly, JP., Sperry, BW., et al.[2019]

The Rheumatic? tool effectively differentiates between individuals developing arthritis and those who do not, with a significant median score difference and an AUC-ROC of 75.3, indicating good predictive ability.

It also distinguishes patients with immune-mediated rheumatic diseases from other conditions, achieving an AUC-ROC of 79.0, although the tool's scoring system requires further optimization for improved sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rheumatic?-A Digital Diagnostic Decision Support Tool for Individuals Suspecting Rheumatic Diseases: A Multicenter Pilot Validation Study. Knevel, R., Knitza, J., Hensvold, A., et al.[2023]

Machine learning methods can effectively supplement traditional knowledge-based algorithms for identifying chronic conditions like hypertension, diabetes, and dyslipidemia, achieving comparable accuracy in a study of over 631,000 individuals.

The study demonstrated that various machine learning techniques, including logistic regression and tree-based models, produced area under the curve (AUC) scores similar to those of conventional methods, indicating their potential for optimizing claims-based algorithms in healthcare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Claims-based algorithms for common chronic conditions were efficiently constructed using machine learning methods. Hara, K., Kobayashi, Y., Tomio, J., et al.[2023]

Tafamidis (Vyndaqel®) is an effective oral treatment for transthyretin amyloidosis with polyneuropathy (ATTR-PN), significantly slowing neurological deterioration and maintaining quality of life in patients with early-stage disease, based on evidence from an 18-month placebo-controlled trial and long-term studies of up to 6 years.

Long-term data from registry studies indicate that tafamidis is safe and well-tolerated, with no new safety concerns, and it provides survival benefits while stabilizing the TTR protein structure in nearly all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafamidis: A Review in Transthyretin Amyloidosis with Polyneuropathy. Lamb, YN., Deeks, ED.[2020]

The diagnosis of transthyretin amyloidosis cardiomyopathy (ATTR-CM) is on the rise due to advancements in imaging techniques and nonbiopsy diagnostic criteria, highlighting the importance of early detection for better patient outcomes.

Tafamidis is increasingly used for treating ATTR-CM, and ongoing phase III trials for new therapies may significantly change treatment options, while in systemic light chain (AL) amyloidosis, improved chemotherapy is enhancing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Diagnosis and Treatment of Cardiac and Renal Amyloidosis. Law, S., Fontana, M., Gillmore, JD.[2022]

In patients with transthyretin amyloidosis with polyneuropathy (ATTR-PN), long-term treatment with tafamidis showed a significant survival benefit, with 85.9% of Val30Met patients alive after 9 years when treated continuously with tafamidis.

For non-Val30Met patients, 75.9% were alive after 8 years, indicating that tafamidis may also be beneficial for this group, although survival rates were lower compared to Val30Met patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years. Merlini, G., Coelho, T., Waddington Cruz, M., et al.[2020]

A machine learning model was developed using data from 348 patients with ankylosing spondylitis (AS) to enhance diagnostic efficiency, identifying seven key blood test factors that can predict AS with high accuracy (AUC values of 0.878 in training and 0.823 in validation cohorts).

The nomogram created from this model can assist orthopedic surgeons in making more personalized treatment decisions for AS patients, potentially leading to earlier and more systematic interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Validation of a Machine Learning-Based Nomogram for Prediction of Ankylosing Spondylitis. Zhu, J., Lu, Q., Liang, T., et al.[2022]

Tafamidis is FDA approved for treating both wild-type and hereditary transthyretin (ATTR) amyloidosis, specifically for cardiomyopathy, while patisiran and inotersen are approved for hereditary ATTR polyneuropathy, highlighting the efficacy of these treatments in managing different forms of the disease.

The review also discusses investigational therapies, such as AG10 and gene silencers like vutrisiran, indicating ongoing research aimed at improving treatment options for ATTR amyloidosis, which is crucial given the disease's complexity and the need for tailored therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Novel Agents and Clinical Considerations in Patients With ATTR Cardiac Amyloidosis. Benbrahim, M., Norman, K., Sanchorawala, V., et al.[2023]

Using stricter diagnostic criteria, such as requiring two medical claims or a claim for a face-to-face encounter, significantly improved the specificity of algorithms for identifying chronic conditions like hypertension and diabetes, increasing it by 0.03 to 0.11.

Incorporating both medical claims and pharmacy claims for relevant medications enhanced the specificity by 0.03 to 0.17 and improved sensitivity by 0.01 to 0.20, demonstrating that more comprehensive data can lead to better identification of beneficiaries with chronic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specificity and sensitivity of claims-based algorithms for identifying members of Medicare+Choice health plans that have chronic medical conditions. Rector, TS., Wickstrom, SL., Shah, M., et al.[2018]

In a study of 648 patients with hereditary (ATTRv) and wild-type (ATTRwt) transthyretin amyloidosis, tafamidis treatment was linked to a significantly longer median survival time without major cardiovascular outcomes, showing its efficacy in a real-life setting.

The results indicated that tafamidis treatment reduced the risk of cardiac decompensation, heart transplant, or death, with a hazard ratio of 0.546, confirming its beneficial impact on patients with cardiomyopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural history and impact of treatment with tafamidis on major cardiovascular outcome-free survival time in a cohort of patients with transthyretin amyloidosis. Bézard, M., Kharoubi, M., Galat, A., et al.[2021]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2305434

Efficacy and Safety of Acoramidis in Transthyretin Amyloid ... In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome.

2. vyndamax.pfizerpro.com vyndamax.pfizerpro.com/about-attrcm/diagnosing-attrcm

Diagnosing ATTR Cardiac Amyloidosis Discover how ATTR-CM is diagnosed, which tests to order, which scans to perform, and get info about VYNDAMAX®, an Rx treatment for ATTR cardiac amyloidosis.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11292761/

Outcomes in Cardiac Transthyretin Amyloidosis and ... Treatment of ATTR‐CA with tafamidis led to substantial improvements of clinical outcome. NYHA classification at treatment initiation is a ...

4. jacc.org jacc.org/doi/10.1016/j.jaccao.2024.12.005

A Multicenter Study of Contemporary Long-Term Tafamidis ... The changing natural history of ATTR-CM has resulted in better outcomes of patients who are being diagnosed earlier and with less symptom burden ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1875213624003231

Tafamidis meglumine early access program in France In conclusion, the EAP provided 2788 patients with ATTR-CM with early access to tafamidis meglumine in France. NYHA class progression and survival were ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11896961/

Efficacy and safety of diflunisal therapy in patients with ... Diflunisal therapy is beneficial in treating ATTR-CA patients but is associated with adverse effects that require therapy discontinuation.

7. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizers-vyndaqelrvyndamaxr-reduced-risk-all-cause-mortality

Pfizer's VYNDAQEL®/VYNDAMAX® Reduced the Risk of ... Pfizer's VYNDAQEL®/VYNDAMAX® Reduced the Risk of All-Cause Mortality by 41% Among Patients with Transthyretin Amyloid Cardiomyopathy, Five-Year ...

8. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.102122

Early Access to Tafamidis for Patients With Transthyretin ... Tafamidis is a TTR stabilizer that inhibits the formation of TTR amyloid and is an approved treatment for patients with ATTR-CM in several ...