Quality initiatives and models of care in patients with pulmonary arterial hypertension: The time has come!

Authors

  • Robert Schilz DO, PhD,

    1. Associate Professor of Medicine, Case University School of Medicine, Director of Pulmonary Vascular Disease and Lung Transplantation, University Hospitals of Cleveland, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106Tel: 216-844-5128 or 216-844-2639Fax: 216-844-2187
      Email: Robert.Schilz@UHhospitals.org
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  • Harrison W. Farber MD

    1. Professor, Boston University School of Medicine
      Director, Pulmonary Hypertension Center, Boston Medical Center, 72 East Concord Street, R-304 Boston, MA 02118
      Tel: 617-638-4860
      Fax: 617-536-8093
      Email: hfarber@bu.edu
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There has been substantial work in the field of pulmonary arterial hypertension (PAH). The number of publications in this field has increased exponentially and the number of trials in new therapeutic agents similarly has seen a dramatic increase in the last 15 years. In spite of this dramatic advance in the field, substantial issues remain in assessing patient care outcome and optimal therapy.

Implementation of care in complex patient groups like PAH can be difficult; however there are several diseases that have similar challenges. Subspecialists with substantial experience in research, diagnosis and management of rare diseases are the norm. Even this pattern of referral, however, is no guarantee that optimal therapy and outcomes will be achieved. There is substantial information in the area of PAH that would suggest we are currently operating in a sub-optimal environment. We will discuss these data and propose possible solutions for the optimization of care in this complex group of patients.

Evaluable data for quality initiatives are not extensive but are available from at least 3 separate sources.

  • 1) Data suggesting that delay of therapy may lead to adverse outcomes
    • a. Epoprostenol therapy and survival in patients with different functional classes.
    • b. Clinical worsening in placebo groups in drug trials.
  • 2) Data suggesting that protocolized approaches to combination therapy may improve patient outcomes.
  • 3) Data showing patient outcomes and therapeutic choices apparently at odds with National and International guidelines.

The first and still the only trial to demonstrate a survival benefit among patients with IPAH is the pivotal epoprostenol trial from 1996. (1) In that trial, with only 12 weeks of treatment, no deaths occurred in the epoprostenol group while 8 deaths occurred in the placebo group. Clearly this short-term mortality in a randomized trial has not been seen since, but the dramatic outcome clearly suggests that delay in therapy in some groups of patients may be fatal. Despite being retrospective and not randomized, one might interpret subsequent case series reports in a similar fashion. Several authors have described survival of patients with IPAH presenting with different functional classes. Overall Kaplan-Meier survival was substantially different between the NYHC III and IV groups. (2–4) Although a number of explanations are possible, one implication is that a patient allowed to deteriorate to NYHC IV before effective therapy is initiated might have a worse outcome. Yet another example of the potential for detrimental outcome may be inferred from clinical worsening data seen in follow-up of patients in randomized, controlled trials randomized to the placebo group. Clinical trials of tadalafil and ambrisentan have shown differences in outcomes in patients receiving placebo that were not improved by subsequent treatment during the time frame examined. (5,6)

Although treatment guidelines summarize current knowledge of therapeutic approaches to PAH, based on scientific rigor and evidence from available clinical trials (7,8), the optimal treatment of patients or patient groups is not known. True evidence based recommendations and guidelines could really only be derived from head to head comparison of agents and sequences of treatment, unlikely given the rare nature of the disease. Nonetheless, some evaluation of the therapeutic approach to PAH patients has been published. In particular, goal directed sequential evaluation of therapy among PAH treated at a referral center has been preliminarily evaluated. In a series of patients initially selected not to receive infusion prostacyclins or transplant, sequential application of therapies were dictated by achievements of functional capacity previously associated with better outcomes (9). Case matched survival appeared better using this approach than in a previous group of patients treated by the same group of physicians. These data suggests again that suboptimal therapeutic choices or failure to achieve treatment goals in a timely fashion may be detrimental.

A third set of data, which is perhaps even more compelling, questions the appropriate use of oral therapies. An abstract presented at the 2008 annual PHA meeting by a specialty pharmacy provider reported deaths in patients treated for PAH. A three year review of 821 patients initiated on oral endothelin receptor antagonist therapy, particularly the 190 patients who died; demonstrated that, 169 died while on oral therapy without exposure to infusion options and that 74% of those patients were never prescribed therapy at a “PAH center”. (10) In a more recent report, approximately >50% of patients in the REVEAL registry were not receiving systemic prostanoids at the time of death. (11) Such reports suggest that a substantial number of patients are not being treated according to current guidelines and may be suffering avoidable adverse outcomes.

Given the serious nature of the disease, the specialized knowledge needed for appropriate diagnosis and treatment, and the growing complexity of the field – has the time come for evaluation of quality of care and models of care in PAH? We say YES! The real question then is how to approach this issue in an equitable and realistic fashion.

Either governments, professional bodies, insurance or occasionally patient centered organizations or consortiums, have generally addressed evaluation and concerns about healthcare quality.

Three main governmental approaches to quality regulation to ensure, maintain or improve outcomes have traditionally been licensing, certification and accreditation. (12) This type of intervention occurs in response to outcomes and cost control typically when current guidelines, therapies and approaches are failing patient needs.

What about licensing? Broad issues of licensing for care of specific medical conditions are an uncommon solution, especially in the field of cardiopulmonary disease. Even advanced disease processes rarely require a specialty license for prescription and treatment with the exception of controlled substance licensing for certain medications in pain or addiction clinics. It seems unlikely that direct governmental licensing would be a valid approach to PAH quality initiatives.

Certification/accreditation seems a reasonable pathway toward improved quality in PAH. Direct certification as an approach to improve quality in medical cardiopulmonary disease varies based on the process evaluated. For example, in a very complex disease process with high mortality and the need for specialized expertise, such as transplantation, certification both from the United Network of Organ Sharing and from Medicare (for reimbursement) is required. Outcome measures are tracked and center performance and volume (published publicly) are used to maintain ongoing certification and eligibility. Initial certification involves documentation of personnel competence, training and experience as well as center resources. Certainly this certification represents a high level of oversight but is an excellent model in specialized service. Current PAH guidelines suggest that patients be referred to subspecialty PAH centers and have begun to define center resources. It would seem that continued refinement of center qualifications and physician competency would be necessary as a starting point for certification, but this process should be possible. However, governmental certification in PAH seems unlikely when compared to the scope and requirements of transplant.

US governmental regulation in cardiopulmonary disease is most obvious in current initiatives in myocardial infarction, heart failure, pneumonia and sepsis monitored by the Joint Commission on Accreditation of Healthcare Organizations. (JCAHO) Under current initiatives, hospital and physician treatment is evaluated against current guidelines with actions and reimbursement tied to practice metrics. This approach is independent of any of the three approaches above but directly monitors adherence to practice guidelines. The relative incidence of PAH pales in comparison to heart failure, pneumonia etc.; as such, it does not seem likely that direct Medicare or governmental involvement in PAH will likely occur, particularly given the small contribution of PAH to morbidity and mortality in the US. In contrast, especially in Europe, governmental support of healthcare is common and referral and availabilities of medication are often tied to subspecialty referral. This type of mandated referral and limited prescriptive availability virtually insures that patients with PAH will be seen at a limited number of centers of excellence in these countries.

Non-governmental certification at lower levels does exist in cardiopulmonary disease, in particular chest pain centers and echocardiography services. This type of certification does not exclude or restrict practice scope, but are viewed as driving care and referral to centers able to demonstrate quality practice metrics. Whether this level of certification is optimal in PAH is not clear.

Non-government insurance and/or reimbursement may be another mechanism by which government or third party (i.e. insurance payers) may be involved in care models and quality monitoring and in some cases, certification. Increased attention to disease-specific approval pathways and requirement of right heart catheterization for confirmation is becoming increasingly adopted by payers. Specific center certification by payers which drives referral in transplant (National Transplant Network, Optum Health for Complex Medical Conditions – previously URN) has not, to our knowledge, been adopted for PAH, but may be tenable in this disease.

Another model of potential quality monitoring for pulmonary disease is patient centered associations, such as the Cystic Fibrosis Foundation, Alpha-1 Association and the Lymphangioleiomyomatosis Society among others. The level of involvement in certification/accreditation is variable: from maintenance of a variably filtered list of providers to formal accreditation of centers with funding, maintenance of data relating to care, public review of data and initiation of quality projects (i.e. Cystic Fibrosis Foundation). Using this model, criteria for physicians and centers, along with ongoing data collection and monitoring are elements of the oversight of treating centers. This paradigm may be a good model for PAH

The future of PAH therapy continues to be encouraging with ongoing drug development and research. A recent article in Advances in Pulmonary Hypertension discussed issues of models of care and provision of optimal care to patients with PAH. (13) Optimizing diagnosis, therapeutic intervention and outcomes should now be considered a paramount interest and necessity in this field.

Disclosure

R. Schilz: Grant/research support: Actelion, Pfizer, Bayer, United Therapeutics, Gilead, GeNO, Novartis. Consultant: Gilead, United Therapeutics, Actelion, Bayer. Speakers Bureau: Gilead, Actelion, United Therapeutics. Data Safety Monitoring Board: Gilead.H. Farber: Advisor/consultant: Actelion, Gilead, United Therapeutics, Novartis, Bristol-Myers, Ikaria. Speakersó Bureau: Actelion, Gilead. Grants: United Therapeutics, Gilead.

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