肺動脈性肺高血圧症市場- 世界の産業規模、シェア、動向、機会、予測、薬剤クラス別、タイプ別、投与経路別、地域別、競合：2020～2030年

肺動脈性肺高血圧症の世界市場は、2024年に82億9,000万米ドルと評価され、2030年のCAGRは6.32%で、予測期間には120億米ドルに達すると予測されています。

肺動脈性肺高血圧症（PAH）は、心臓から肺に血液を運ぶ肺動脈の高血圧を特徴とする、まれではあるが深刻な病状です。この疾患は、肺動脈の狭窄と硬化を引き起こし、血液を送り出すために心臓の働きを低下させ、最終的には心不全を引き起こします。世界の肺動脈性肺高血圧症市場には、PAHの管理・治療を目的とした医薬品、医療機器、治療アプローチなどが含まれます。

北米市場は、医療的理解の進歩、革新的な治療法、PAHに対する認識の高まりなどを背景に、最近の動向は著しいです。同市場の成長に寄与する主要因としては、肥満や座りがちなライフスタイルなどの危険因子によるPAHの有病率の上昇、診断能力の向上、患者とヘルスケア専門家の両方における認知度の向上などが挙げられます。PAH管理においては、薬剤介入が重要な役割を果たしています。プロスタサイクリンアナログ、エンドセリン受容体拮抗薬、ホスホジエステラーゼ5型阻害剤など、PAH発症に関与する特定の経路を標的とした薬剤が開発されています。これらの薬剤は、血管を拡大し、動脈圧を下げ、息切れや疲労などの症状を緩和することを目的としています。

主要市場促進要因

肺動脈性肺高血圧症（PAH）の有病率と認知度の向上

主要市場課題

高い治療費

主要市場動向

個別化医療

目次

第1章 概要

第2章 調査手法

第3章 エグゼクティブサマリー

第4章 顧客の声

第5章 世界の肺動脈性肺高血圧症市場展望

• 市場規模・予測
  • 金額別
• 市場シェア・予測
  • 薬剤クラス別（プロスタサイクリンとプロスタサイクリン類似体、カルシウムチャネル遮断薬、ホスホジエステラーゼ5、エンドセリン受容体拮抗薬など）
  • タイプ別（ブランド、ジェネリック）
  • 投与経路別（経口、静脈内/皮下、吸入）
  • 企業別（2024年）
  • 地域別
• 市場マップ

第6章 北米の肺動脈性肺高血圧症市場展望

• 市場規模・予測
• 市場シェア・予測
• 北米：国別分析
  • 米国
  • メキシコ
  • カナダ

第7章 欧州の肺動脈性肺高血圧症市場展望

• 市場規模・予測
• 市場シェア・予測
• 欧州：国別分析
  • フランス
  • ドイツ
  • 英国
  • イタリア
  • スペイン

第8章 アジア太平洋の肺動脈性肺高血圧症市場展望

• 市場規模・予測
• 市場シェア・予測
• アジア太平洋：国別分析
  • 中国
  • インド
  • 韓国
  • 日本
  • オーストラリア

第9章 南米の肺動脈性肺高血圧症市場展望

• 市場規模・予測
• 市場シェア・予測
• 南米：国別分析
  • ブラジル
  • アルゼンチン
  • コロンビア

第10章 中東・アフリカの肺動脈性肺高血圧症市場展望

• 市場規模・予測
• 市場シェア・予測
• 中東・アフリカ：国別分析
  • 南アフリカ
  • サウジアラビア
  • アラブ首長国連邦

第11章 市場力学

• 促進要因
• 課題

第12章 市場動向と発展

• 製品上市
• 合併と買収

第13章 PESTEL分析

第14章 ポーターのファイブフォース分析

• 産業内の競合
• 新規参入の可能性
• サプライヤーの力
• 顧客の力
• 代替品の脅威

第15章 競合情勢

• Gilead Sciences, Inc.
• Viatris Inc.
• Sandoz Inc.（Novartis）
• Johnson & Johnson
• Sun Pharmaceutical Industries, Inc.
• Lupin Pharmaceuticals, Inc.
• GlaxoSmithKline LLC
• Johnson & Johnson
• Bayer AG
• United Therapeutics Corporation

第16章 戦略的提言

第17章 調査会社について・免責事項

Global Pulmonary Arterial Hypertension Market was valued at USD 8.29 billion in 2024 and is expected to reach USD 12.00 billion in the forecast period with a CAGR of 6.32% through 2030. Pulmonary Arterial Hypertension (PAH) is a rare but serious medical condition characterized by high blood pressure in the pulmonary arteries, which carry blood from the heart to the lungs. This condition leads to the narrowing and stiffening of these arteries, causing the heart to work harder to pump blood, ultimately leading to heart failure. The Global Pulmonary Arterial Hypertension Market encompasses a range of pharmaceuticals, medical devices, and treatment approaches aimed at managing and treating PAH.

The market has witnessed significant developments in recent years, driven by advancements in medical understanding, innovative therapies, and increased awareness of PAH. Key factors contributing to the growth of this market include a rising prevalence of PAH due to risk factors like obesity and sedentary lifestyles, as well as improved diagnostic capabilities and awareness among both patients and healthcare professionals. Pharmaceutical interventions play a crucial role in PAH management. Drugs targeting specific pathways involved in PAH pathogenesis have been developed, including prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. These medications aim to dilate blood vessels, reduce arterial pressure, and alleviate symptoms such as shortness of breath and fatigue.

Key Market Drivers

Increasing Prevalence and Awareness of Pulmonary Arterial Hypertension (PAH)

The increasing prevalence of Pulmonary Arterial Hypertension (PAH) and rising awareness of its severity are powerful growth drivers for the PAH market. Globally, PAH prevalence has nearly doubled since 1990, reaching approximately 191,800 cases in 2021, marking an 81.5% increase This rise is fueled by factors such as aging populations and lifestyle-related risks like obesity and sedentary behavior, increasing the need for early and effective diagnosis and management. Simultaneously, awareness campaigns have become more prominent, supported by public health entities and patient advocacy groups. A recent global initiative in May 2024 involved over 80 organizations, amplifying PAH visibility and emphasizing early screening. Meanwhile, improved medical education efforts and patient-targeted campaigns like Merck's "Outnumber PAH" have significantly reduced diagnosis delays (which once took over two years), ensuring patients seek timely care. Early detection spurs demand for diagnostics, specialist treatment options, and long-term patient support. These combined forces rising prevalence and heightened disease awareness have fostered increased research funding and attracted pharmaceutical investment in innovative therapies. As countries bolster screening programs and healthcare access for at-risk groups, the market is propelled by the need for advanced diagnostics, tailored medications, and comprehensive disease management strategies, ultimately benefiting both patients and industry innovation.

Moreover, the growing adoption of digital health tools and real-world data collection is enhancing the understanding and management of Pulmonary Arterial Hypertension (PAH). With the integration of electronic health records, wearable health monitors, and telemedicine, patients with suspected or diagnosed PAH are now monitored more closely and efficiently. This has led to improved adherence to treatment protocols and timely therapeutic adjustments. In countries like Japan and Germany, initiatives that combine digital diagnostics with centralized PAH registries have resulted in earlier interventions and improved patient outcomes. Additionally, real-world evidence collected from diverse patient populations is fueling post-marketing surveillance and guiding regulatory decisions for emerging therapies. As digital technologies continue to bridge gaps in diagnosis, monitoring, and patient education, the PAH market is expected to witness a robust transformation toward personalized and proactive care.

Key Market Challenges

High Treatment Costs

High treatment costs stand as a significant challenge in the Pulmonary Arterial Hypertension (PAH) Market, impacting both patients and healthcare systems. PAH is a chronic and progressive disease that requires ongoing and often complex medical interventions, including medications, medical devices, and specialized care. The financial burden associated with these treatments can be overwhelming for patients and their families, creating barriers to accessing necessary care and potentially compromising treatment adherence.

The cost of PAH medications is a major concern. Many of the medications used to manage PAH are high-priced specialty drugs, some of which require lifelong administration. These medications target specific pathways involved in the disease and can help alleviate symptoms, improve exercise capacity, and slow disease progression. However, the exorbitant costs of these treatments can lead to financial strain, forcing patients to make difficult choices between their health and other essential expenses. Furthermore, the need for comprehensive care compounds the financial challenge. PAH often requires a multidisciplinary approach, involving specialists, diagnostic tests, monitoring, and follow-up appointments. These additional healthcare expenses can accumulate quickly, placing a heavy financial burden on patients and their families. Access to specialized centers equipped to provide comprehensive care may also be limited in some regions, further exacerbating the challenge. Healthcare systems and insurers also feel the impact of high treatment costs. The provision of effective PAH care strains budgets and resources, potentially limiting the availability of these treatments to those who need them. Payers may face difficult decisions about coverage and reimbursement, potentially leading to disparities in access to care based on patients' ability to pay.

The high treatment costs associated with PAH underscore the need for a comprehensive approach to address this challenge. Collaborative efforts among pharmaceutical companies, healthcare providers, policymakers, and patient advocacy groups are essential to finding solutions that balance patients' access to effective treatments with the financial sustainability of healthcare systems. Initiatives such as patient assistance programs, value-based pricing models, and increased transparency in drug pricing can help alleviate some of the financial burdens faced by patients. Overall, the high treatment costs in the Pulmonary Arterial Hypertension (PAH) Market create substantial challenges for patients, families, and healthcare systems. Finding innovative ways to ensure affordable access to effective treatments while maintaining the financial viability of healthcare systems is a critical endeavor that requires the collective efforts of all stakeholders involved.

Key Market Trends

Personalized medicine

Personalized medicine has emerged as a transformative trend in the Pulmonary Arterial Hypertension (PAH) Market. This innovative approach tailors medical care to the individual characteristics of each patient, offering treatments that are optimized based on genetic, molecular, and clinical profiles. In the context of PAH, personalized medicine is revolutionizing how the disease is diagnosed, managed, and treated, leading to improved outcomes and a more patient-centric approach. One of the keyways personalized medicines is impacting the PAH market is through precise diagnostics. Genetic testing and molecular profiling enable healthcare providers to identify specific genetic mutations and biomarkers associated with PAH. This information allows for early and accurate diagnosis, enabling timely interventions that can prevent disease progression. Additionally, identifying genetic factors that influence treatment response helps healthcare providers select the most effective therapies for each patient. The concept of targeted therapies aligns perfectly with personalized medicine. Instead of adopting a one-size-fits-all approach, healthcare providers can now prescribe medications that are specifically designed to address the molecular mechanisms driving an individual's PAH. This not only enhances the efficacy of treatment but also reduces the risk of adverse effects. For example, drugs that target specific pathways, such as endothelin receptor antagonists, can be selected based on a patient's genetic predisposition and disease profile. Furthermore, the integration of data-driven technologies and electronic health records allows for real-time monitoring of patients' health status. This continuous monitoring provides valuable insights into disease progression and response to treatment, enabling prompt adjustments to therapies as needed. Patients benefit from personalized care plans that consider their unique medical history, lifestyle factors, and treatment preferences.

Personalized medicine also encourages patient engagement and empowerment. Patients become active participants in their care, making informed decisions based on their genetic and clinical information. This shift in the patient-provider relationship fosters a sense of ownership over one's health and encourages adherence to treatment plans. As the field of personalized medicine continues to advance, the PAH market is set to experience further growth. Collaborations between researchers, pharmaceutical companies, and healthcare providers will drive the development of new targeted therapies and diagnostic tools. Regulatory agencies are recognizing the importance of personalized medicine and are streamlining approval processes for these innovative treatments.

Key Market Players

• Gilead Sciences, Inc.
• Viatris Inc.
• Sandoz Inc. (Novartis)
• Johnson & Johnson
• Sun Pharmaceutical Industries, Inc.
• Lupin Pharmaceuticals, Inc.
• GlaxoSmithKline LLC
• Johnson & Johnson
• Bayer AG
• United Therapeutics Corporation

Report Scope:

In this report, the Global Pulmonary Arterial Hypertension Market has been segmented into the following categories, in addition to the industry trends which have also been detailed below:

Pulmonary Arterial Hypertension Market, By Drug Class:

• Prostacyclin and Prostacyclin Analogs
• Calcium Channel Blockers
• Phosphodiesterase 5
• Endothelin Receptor Antagonist
• Others

Pulmonary Arterial Hypertension Market, By Type:

• Branded
• Generics

Pulmonary Arterial Hypertension Market, By Route Of Administration:

• Oral
• Intravenous/ Subcutaneous
• Inhalational

Pulmonary Arterial Hypertension Market, By region:

• North America
  • United States
  • Canada
  • Mexico
• Asia-Pacific
  • China
  • India
  • South Korea
  • Australia
  • Japan
• Europe
  • Germany
  • France
  • United Kingdom
  • Spain
  • Italy
• South America
  • Brazil
  • Argentina
  • Colombia
• Middle East & Africa
  • South Africa
  • Saudi Arabia
  • UAE

Competitive Landscape

Company Profiles: Detailed analysis of the major companies present in the Global Pulmonary Arterial Hypertension Market.

Available Customizations:

Global Pulmonary Arterial Hypertension Market report with the given market data, TechSci Research offers customizations according to a company's specific needs. The following customization options are available for the report:

Company Information

• Detailed analysis and profiling of additional market players (up to five).

Table of Contents

1. Product Overview

• 1.1. Market Definition
• 1.2. Scope of the Market
  • 1.2.1. Markets Covered
  • 1.2.2. Years Considered for Study
  • 1.2.3. Key Market Segmentations

2. Research Methodology

• 2.1. Objective of the Study
• 2.2. Baseline Methodology
• 2.3. Key Industry Partners
• 2.4. Major Association and Secondary Sources
• 2.5. Forecasting Methodology
• 2.6. Data Triangulation & Validation
• 2.7. Assumptions and Limitations

3. Executive Summary

• 3.1. Overview of the Market
• 3.2. Overview of Key Market Segmentations
• 3.3. Overview of Key Market Players
• 3.4. Overview of Key Regions/Countries
• 3.5. Overview of Market Drivers, Challenges, Trends

4. Voice of Customers

5. Global Pulmonary Arterial Hypertension Market Outlook

• 5.1. Market Size & Forecast
  • 5.1.1. By Value
• 5.2. Market Share & Forecast
  • 5.2.1. By Drug Class (Prostacyclin and Prostacyclin Analogs, Calcium Channel Blockers, Phosphodiesterase 5, Endothelin Receptor Antagonist and Others)
  • 5.2.2. By Type (Branded, Generics)
  • 5.2.3. By Route Of Administration (Oral, Intravenous/ Subcutaneous, Inhalational)
  • 5.2.4. By Company (2024)
  • 5.2.5. By Region
• 5.3. Market Map

6. North America Pulmonary Arterial Hypertension Market Outlook

• 6.1. Market Size & Forecast
  • 6.1.1. By Value
• 6.2. Market Share & Forecast
  • 6.2.1. By Drug Class
  • 6.2.2. By Type
  • 6.2.3. By Route Of Administration
  • 6.2.4. By Country
• 6.3. North America: Country Analysis
  • 6.3.1. United States Pulmonary Arterial Hypertension Market Outlook
    • 6.3.1.1. Market Size & Forecast
      • 6.3.1.1.1. By Value
    • 6.3.1.2. Market Share & Forecast
      • 6.3.1.2.1. By Drug Class
      • 6.3.1.2.2. By Type
      • 6.3.1.2.3. By Route Of Administration
  • 6.3.2. Mexico Pulmonary Arterial Hypertension Market Outlook
    • 6.3.2.1. Market Size & Forecast
      • 6.3.2.1.1. By Value
    • 6.3.2.2. Market Share & Forecast
      • 6.3.2.2.1. By Drug Class
      • 6.3.2.2.2. By Type
      • 6.3.2.2.3. By Route Of Administration
  • 6.3.3. Canada Pulmonary Arterial Hypertension Market Outlook
    • 6.3.3.1. Market Size & Forecast
      • 6.3.3.1.1. By Value
    • 6.3.3.2. Market Share & Forecast
      • 6.3.3.2.1. By Drug Class
      • 6.3.3.2.2. By Type
      • 6.3.3.2.3. By Route Of Administration

7. Europe Pulmonary Arterial Hypertension Market Outlook

• 7.1. Market Size & Forecast
  • 7.1.1. By Value
• 7.2. Market Share & Forecast
  • 7.2.1. By Drug Class
  • 7.2.2. By Type
  • 7.2.3. By Route Of Administration
  • 7.2.4. By Country
• 7.3. Europe: Country Analysis
  • 7.3.1. France Pulmonary Arterial Hypertension Market Outlook
    • 7.3.1.1. Market Size & Forecast
      • 7.3.1.1.1. By Value
    • 7.3.1.2. Market Share & Forecast
      • 7.3.1.2.1. By Drug Class
      • 7.3.1.2.2. By Type
      • 7.3.1.2.3. By Route Of Administration
  • 7.3.2. Germany Pulmonary Arterial Hypertension Market Outlook
    • 7.3.2.1. Market Size & Forecast
      • 7.3.2.1.1. By Value
    • 7.3.2.2. Market Share & Forecast
      • 7.3.2.2.1. By Drug Class
      • 7.3.2.2.2. By Type
      • 7.3.2.2.3. By Route Of Administration
  • 7.3.3. United Kingdom Pulmonary Arterial Hypertension Market Outlook
    • 7.3.3.1. Market Size & Forecast
      • 7.3.3.1.1. By Value
    • 7.3.3.2. Market Share & Forecast
      • 7.3.3.2.1. By Drug Class
      • 7.3.3.2.2. By Type
      • 7.3.3.2.3. By Route Of Administration
  • 7.3.4. Italy Pulmonary Arterial Hypertension Market Outlook
    • 7.3.4.1. Market Size & Forecast
      • 7.3.4.1.1. By Value
    • 7.3.4.2. Market Share & Forecast
      • 7.3.4.2.1. By Drug Class
      • 7.3.4.2.2. By Type
      • 7.3.4.2.3. By Route Of Administration
  • 7.3.5. Spain Pulmonary Arterial Hypertension Market Outlook
    • 7.3.5.1. Market Size & Forecast
      • 7.3.5.1.1. By Value
    • 7.3.5.2. Market Share & Forecast
      • 7.3.5.2.1. By Drug Class
      • 7.3.5.2.2. By Type
      • 7.3.5.2.3. By Route Of Administration

8. Asia-Pacific Pulmonary Arterial Hypertension Market Outlook

• 8.1. Market Size & Forecast
  • 8.1.1. By Value
• 8.2. Market Share & Forecast
  • 8.2.1. By Drug Class
  • 8.2.2. By Type
  • 8.2.3. By Route Of Administration
  • 8.2.4. By Country
• 8.3. Asia-Pacific: Country Analysis
  • 8.3.1. China Pulmonary Arterial Hypertension Market Outlook
    • 8.3.1.1. Market Size & Forecast
      • 8.3.1.1.1. By Value
    • 8.3.1.2. Market Share & Forecast
      • 8.3.1.2.1. By Drug Class
      • 8.3.1.2.2. By Type
      • 8.3.1.2.3. By Route Of Administration
  • 8.3.2. India Pulmonary Arterial Hypertension Market Outlook
    • 8.3.2.1. Market Size & Forecast
      • 8.3.2.1.1. By Value
    • 8.3.2.2. Market Share & Forecast
      • 8.3.2.2.1. By Drug Class
      • 8.3.2.2.2. By Type
      • 8.3.2.2.3. By Route Of Administration
  • 8.3.3. South Korea Pulmonary Arterial Hypertension Market Outlook
    • 8.3.3.1. Market Size & Forecast
      • 8.3.3.1.1. By Value
    • 8.3.3.2. Market Share & Forecast
      • 8.3.3.2.1. By Drug Class
      • 8.3.3.2.2. By Type
      • 8.3.3.2.3. By Route Of Administration
  • 8.3.4. Japan Pulmonary Arterial Hypertension Market Outlook
    • 8.3.4.1. Market Size & Forecast
      • 8.3.4.1.1. By Value
    • 8.3.4.2. Market Share & Forecast
      • 8.3.4.2.1. By Drug Class
      • 8.3.4.2.2. By Type
      • 8.3.4.2.3. By Route Of Administration
  • 8.3.5. Australia Pulmonary Arterial Hypertension Market Outlook
    • 8.3.5.1. Market Size & Forecast
      • 8.3.5.1.1. By Value
    • 8.3.5.2. Market Share & Forecast
      • 8.3.5.2.1. By Drug Class
      • 8.3.5.2.2. By Type
      • 8.3.5.2.3. By Route Of Administration

9. South America Pulmonary Arterial Hypertension Market Outlook

• 9.1. Market Size & Forecast
  • 9.1.1. By Value
• 9.2. Market Share & Forecast
  • 9.2.1. By Drug Class
  • 9.2.2. By Type
  • 9.2.3. By Route Of Administration
  • 9.2.4. By Country
• 9.3. South America: Country Analysis
  • 9.3.1. Brazil Pulmonary Arterial Hypertension Market Outlook
    • 9.3.1.1. Market Size & Forecast
      • 9.3.1.1.1. By Value
    • 9.3.1.2. Market Share & Forecast
      • 9.3.1.2.1. By Drug Class
      • 9.3.1.2.2. By Type
      • 9.3.1.2.3. By Route Of Administration
  • 9.3.2. Argentina Pulmonary Arterial Hypertension Market Outlook
    • 9.3.2.1. Market Size & Forecast
      • 9.3.2.1.1. By Value
    • 9.3.2.2. Market Share & Forecast
      • 9.3.2.2.1. By Drug Class
      • 9.3.2.2.2. By Type
      • 9.3.2.2.3. By Route Of Administration
  • 9.3.3. Colombia Pulmonary Arterial Hypertension Market Outlook
    • 9.3.3.1. Market Size & Forecast
      • 9.3.3.1.1. By Value
    • 9.3.3.2. Market Share & Forecast
      • 9.3.3.2.1. By Drug Class
      • 9.3.3.2.2. By Type
      • 9.3.3.2.3. By Route Of Administration

10. Middle East and Africa Pulmonary Arterial Hypertension Market Outlook

• 10.1. Market Size & Forecast
  • 10.1.1. By Value
• 10.2. Market Share & Forecast
  • 10.2.1. By Drug Class
  • 10.2.2. By Type
  • 10.2.3. By Route Of Administration
  • 10.2.4. By Country
• 10.3. MEA: Country Analysis
  • 10.3.1. South Africa Pulmonary Arterial Hypertension Market Outlook
    • 10.3.1.1. Market Size & Forecast
      • 10.3.1.1.1. By Value
    • 10.3.1.2. Market Share & Forecast
      • 10.3.1.2.1. By Drug Class
      • 10.3.1.2.2. By Type
      • 10.3.1.2.3. By Route Of Administration
  • 10.3.2. Saudi Arabia Pulmonary Arterial Hypertension Market Outlook
    • 10.3.2.1. Market Size & Forecast
      • 10.3.2.1.1. By Value
    • 10.3.2.2. Market Share & Forecast
      • 10.3.2.2.1. By Drug Class
      • 10.3.2.2.2. By Type
      • 10.3.2.2.3. By Route Of Administration
  • 10.3.3. UAE Pulmonary Arterial Hypertension Market Outlook
    • 10.3.3.1. Market Size & Forecast
      • 10.3.3.1.1. By Value
    • 10.3.3.2. Market Share & Forecast
      • 10.3.3.2.1. By Drug Class
      • 10.3.3.2.2. By Type
      • 10.3.3.2.3. By Route Of Administration

11. Market Dynamics

• 11.1. Drivers
• 11.2. Challenges

12. Market Trends & Developments

• 12.1. Recent Developments
• 12.2. Product Launches
• 12.3. Mergers & Acquisitions

13. PESTLE Analysis

14. Porter's Five Forces Analysis

• 14.1. Competition in the Industry
• 14.2. Potential of New Entrants
• 14.3. Power of Suppliers
• 14.4. Power of Customers
• 14.5. Threat of Substitute Product

15. Competitive Landscape

• 15.1. Gilead Sciences, Inc.
  • 15.1.1. Business Overview
  • 15.1.2. Company Snapshot
  • 15.1.3. Products & Services
  • 15.1.4. Financials (As Reported)
  • 15.1.5. Recent Developments
  • 15.1.6. Key Personnel Details
  • 15.1.7. SWOT Analysis
• 15.2. Viatris Inc.
• 15.3. Sandoz Inc. (Novartis)
• 15.4. Johnson & Johnson
• 15.5. Sun Pharmaceutical Industries, Inc.
• 15.6. Lupin Pharmaceuticals, Inc.
• 15.7. GlaxoSmithKline LLC
• 15.8. Johnson & Johnson
• 15.9. Bayer AG
• 15.10. United Therapeutics Corporation

16. Strategic Recommendations

17. About Us & Disclaimer