Adjuvant Chemotherapy

Historically, primary treatment of breast cancer by surgery, or surgery with radiation, assumed that the cancer was physically confined to the breast. But, high recurrence after treatment led clinicians to believe that submicroscopic or occult cancers typically spread from the primary tumor to other areas of the body before diagnosis and primary treatment with surgery and radiotherapy (I. C. Henderson 1985, p. 140). Adjuvant therapy the use of cytotoxic drugs after primary therapy developed as...

Growth Factors

Human growth factors, also known as colony stimulating factors (CSFs) were developed in the 1980s to stimulate the production of blood cells. These factors can help blood-forming tissue recover from the effects of chemotherapy and radiation therapy. Two forms of CSF were studied as Investigational New Drugs (INDs) granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the 1980s, these drugs were made available for clinical research under...

Research Methodologies

We used a number of different methodologies in the preparation of this book. We made extensive use of semistructured interviews with key actors for every stage of the research and analysis. Some individuals were interviewed more than once, and we often established a continuing conversation with some individuals. Although some interviews were conducted over the telephone, most were face-to-face, and some involved full-day site visits. Most interviews identify the interviewee and the date of the...

The Evaluation of New Treatments

Important segments of medicine, including oncology, were moving in a direction opposite that of insurers regarding the evaluation of new treatments. Although this movement focused on early access to new drugs, not procedures as we have described HDC ABMT, the general principles shaped perceptions within the field of oncology and bore directly on HDC ABMT. The highly regulated process of new drug development begins with preclinical laboratory and animal studies and proceeds to extensive testing...

The Courts Initial Response

The first cases challenging insurers' refusal to cover the procedure were filed in the late 1980s, shortly after HDC ABMT initially attracted interest as a therapy for breast cancer but before much was known about it. Consequently, it is not surprising that in these early cases (before 1990) courts supported the insurers' determination that the treatment was experimental.29 These relatively short opinions focused on the fact that HDC ABMT was still in phase 3 clinical trials (in which the...

Litigation Issues and Trends

After their health insurers refused to pay for HDC ABMT on the grounds that there was no evidence that HDC ABMT was superior to standard-dose chemotherapy, many women responded by seeking insurance coverage of the procedure through the judicial system. In most cases, they filed a motion for a preliminary injunction to compel their insurer to provide coverage in advance of the treatment. In other cases, the women underwent the therapy, and then they or, all too often, their estate sued their...

High Dose Chemotherapy

The appropriate dosage for cancer chemotherapy has long been debated within oncology. In 1980, Frei and Canellos argued that the importance of the dose of chemotherapy drugs was insufficiently appreciated. Chemotherapy drugs were so toxic that any suggestion that the dose-response curve was not steep or that lower doses were as effective as higher ones led oncologists to administer lower doses. They argued that the toxicity of antitumor agents was strongly dose related for both tumor and normal...

Phase 2 Studies

Phase 1 studies in oncology seek to demonstrate the tolerable doses of chemother-apeutic agents. Phase 2 studies constitute an area of experimentation in which researchers examine promising new treatments. These studies provide the initial test of therapeutic benefit, further refine knowledge of toxicity and related issues of dosage, and basically generate the hypotheses for further investigation. Typically, phase 2 studies are conducted at single institutions, involve relatively few patients,...

Resolution and Postscript

In 1999, several randomized controlled studies reported that HDC ABMT was no more effective than standard-dose chemotherapy (e.g., Stadtmauer et al. 2000 see also chapter 8). An editorial accompanying one study concluded as follows T o a reasonable degree of probability, this form of treatment for women with metastatic breast cancer has been proved to be ineffective and should be abandoned in favor of well-justified alternative approaches (Lippman 2000, p. 1120). Predictably, requests for the...

Stamp I Stamp Ii Stamp Iii Stamp Iv Stamp V

Cyclophosphamide, cisplatin, carmustine (BCNU) Ifosfamide, carboplatin, etoposide Cyclophosphamide, thiotepa (antibiotic protocol) Cyclophosphamide, thiotepa, carboplatin a The letter sequence in a combination regimen corresponds to the sequence in which the individual chemotherapy drugs are administered. disease, suggesting that the dose-response curve would be steeper in the adjuvant (or early-stage) setting than in the metastatic setting. This appeared to be true for the CMF regimen in...

Oncology Legitimates an Experimental Procedure

The limited commitment to randomized trials was reflected in several statements that emanated from the AMA. Its Diagnostic and Therapeutic Technology Assessment (DATTA) program solicited the opinions of clinicians rather than systematically reviewing the literature. In an early 1990 poll of 45 oncologists on ABMT, an overwhelming majority rated the safety and effectiveness of ABMT as established or promising (AMA DATTA 1990). Although the report limited itself to acute lymphocytic leukemia,...

Other Claims for Relief

A few plaintiffs tried more creative approaches in their efforts to enjoin their insurer from denying coverage, albeit not with great success. In Reger v. Espy, the plaintiff argued that denial of coverage of HDC ABMT violated Title VII of the Civil Rights Act of 1964 in that exclusion of the treatment has a disparate impact on females.105 The court rejected that argument, noting that i t is clear from the language of the Plan . . . that HDC-ABMT benefits are not available for most types of...

Health Insurers and Randomized Clinical Trials

Health insurers responded to the experimental, expensive, and visible nature of HDC ABMT in three ways in 1988-1990. Many denied coverage for the procedure some conducted formal technology assessments still others financed randomized trials directly in 1990 or shortly after created new ways to do so. But, no matter how they responded, insurers were vulnerable to the charge of acting in their financial self-interest in their coverage denials, their resistance to paying for clinical trials, and...

Breast Cancer and Its Treatment

It is the second leading cause of cancer death among women (representing 15 of all cancer deaths), compared to 25 of cancer deaths from lung cancer (American Cancer Society ACS 2004). Estimated deaths from breast cancer in 2003 were 39,800 for women and 400 for men. Mortality rates for breast cancer declined significantly in recent years, mostly among young women, both white and black, falling 1.4 annually in 1989-1995 and then at a rate of 3.2 annually....

Bone Marrow Transplantation

Bone marrow transplantation is an offshoot of whole organ transplantation.2 Allogeneic BMT involves infusing marrow cells from an immunologically compatible donor to the patient being treated. It had been applied therapeutically mainly to hematologic disorders and was described as curative for severe immunodeficiency, aplastic anemia, thalassemia, and leukemia and lymphoma (Hansen et al. 1989). Autologous BMT involves extracting a patient's marrow, preserving it through a freezing process,...

Combination Chemotherapy

A basic limitation of cancer therapy is the resistance of tumors to cytotoxic drugs (I. C. Henderson et al. 1988). Combination chemotherapy developed as a way to overcome resistance. By the 1970s, it had been shown that metastatic breast cancer was moderately sensitive to single-agent chemotherapy (DeVita and Schein 1973). Several groups of cytotoxic agents were identified as active against metastatic breast cancer, including the alkylating agents (cyclophosphamide, thiotepa, L-phenylalanine...

Cases Subject to State

Only policies negotiated directly between the patient and an insurance underwriter are governed by the law of the state in which the agreement is consummated. State courts have traditionally viewed health insurance policies as contracts of adhesion rather than negotiated agreements and therefore have construed ambiguous coverage provisions in favor of the policyholder (Giese 1996, pp. 215-216). As such, state court decisions reviewing denial of coverage for HDC ABMT tended to favor the...

The Ambivalent Commitment of Medicine to the Gold Standard

Randomized controlled trials are often described as the gold standard by which reliable medical knowledge is validated. They constitute the most persuasive way to test the validity of hypotheses that emerge from phase 2 studies. Randomization is central to ruling out the confounding factors, especially patient selection biases that confound comparisons of an investigational therapy with historical controls, and treatment biases that may reflect practice at a single institution. Oncology is...

Recognition of a New Procedure

The recognition of a new drug follows a highly regulated and highly visible process. The progress of a new drug through clinical trials, the FDA's review, and the recommendation of an advisory committee are all followed closely in the trade press. The FDA approves or disapproves a drug on a date specific in a letter to the commercial sponsor, and announcement of that is also widely reported and often has an immediate effect on that firm's stock price. The marketing launch of a newly approved...

Whats in a Name

When first developed, HDC ABMT was often described as BMT or ABMT (or sometimes AuBMT). In time, the procedure came to be referred to as HDC ABMT. This acknowledges that treatment is HDC made possible by transplantation, a rescue procedure from an otherwise lethal dose of chemotherapy. Autologous refers to bone marrow from the patient herself allogeneic bone marrow is donated by another individual. As the procedure developed, treatment was also described as HDC with peripheral blood (or...

Clear Exclusions by Insurers

In response to the rulings in favor of breast cancer patients seeking coverage for HDC ABMT, insurers quickly began to draft their policies in ways that made the exclusion of the treatment hard to dispute, even under the de novo standard (as described in the section ERISA Standards of Review). By 1993, circuit courts had faced a number of so-called clear-drafting cases (ERISA Litigation Reporter 1996). In one case, the plan did not include breast cancer in its list of specific cancers for which...

The Story in Brief A Fateful Branching

What do these cases illustrate They indicate the intense hope and fear that drove women with a diagnosis of breast cancer to seek an experimental treatment presumed to offer better prospects than conventional therapy. They suggest the dependence of women on the advice they receive from their physicians, especially when a treatment is characterized as the only chance for a cure. The cases show how the demands of these women were expressed forcefully to and through families, physicians, clergy,...

Arbitrary and Capricious Standard in FEHBA and Champus Cases

The FEHBA authorizes the OPM to contract with private insurance companies to provide health benefits to all federal employees.83 The OPM has final authority to decide benefits and exclusions in all FEHBA plans. CHAMPUS is a health benefits program established by Congress to provide coverage to retired military personnel and their dependents.84 CHAMPUS, which is financed through funds appropriated by Congress, contracts with MCOs to provide coverage for its beneficiaries.85 In reviewing coverage...

The Media

The media (newspapers, magazines, and television) were also a major force in the use of HDC ABMT for breast cancer. They reported the story as women being denied access to lifesaving treatment by insurance companies interested only in financial considerations. Langer (2004) recalled how that organization had attempted to influence the general reporting of breast cancer in the late 1980s and early 1990s. The overlay to all of this is that huge tensions were created by the advent and growth of...

The Transplanters

Surgeons dominated the treatment of cancer until recent decades. Radiologists came to play a supporting role after World War II. Hematologists developed a similar role for leukemias and lymphomas. Only in the 1970s did medical oncology emerge as the primary cancer-treating specialty. Each group had its own treatment technology (surgery, radiotherapy, and chemotherapy) that depended partly on the prevailing concept of cancer and partly on the empirical outcomes of treatment. As oncology...

Randomized Clinical Trials Are Authorized

Payment for clinical research was a discussion in the abstract until HDC ABMT came into focus, Sue Gleeson of the BCBSA recalled (Gleeson 2002). A series of meetings in 1988-1990 forged a response to the specific issues raised by the new procedure. The medical directors of the Blue Cross Blue Shield plans met in fall 1988. Guests included Robert Wittes and Mary McCabe from the NCI and Karen Antman of Dana-Farber, who spoke about breast cancer and ABMT (Aronson 2002). Antman's message was that...

Acknowledgments

We owe an immense debt of gratitude to many individuals and regret our inability to thank them more than we do here. We thank I. Craig Henderson for help in understanding the clinical issues and for placing them in a larger context of both oncology and policy. We thank the many other clinical researchers we acknowledge as interviewees or whose papers we cite. We thank William P. Peters for a gracious interview toward the end of our research. We thank the many women, some of whom we cite in the...

Health Insurance and Medicine in the 1980s

Health insurers have been challenged repeatedly in recent decades to respond to new medical treatments, technologies, and innovations. Slowly and haltingly they have developed institutions and strategies that ask for evidence of medical effectiveness as an input to coverage decisions. These developments have often brought them into conflict with medical innovators, as they did in the HDC ABMT case. Health insurance developed in the pre- and post-World War II period well before medical research...