Getting Genomics Drugs to Market
Introduction
One of the ultimate goals of clinical transformation is bringing technology to the research component of health care organizations. This is an example of how clinical transformation can bring benefit to an organization that focuses on the academic side of the vision.
This paper is based on interviews with 20 leading academic medical centers (AMCs), which report the following pertinent facts:
- 60 percent report having an electronic medical record (EMR) in place.
- 40 percent of interviewees report that patient genotypes are stored only in standalone databases.
The Pharmacogenomics Era Beckons
Money is flowing into pharmacogenomics, the science of employing genetic data to understand differences in drug response and tailor products to patient subgroups. Drug firms are putting aside blockbuster worries and banking samples for analysis, driven by market opportunity and regulatory pressure. But if firms are to meet commonly cited timelines for introducing new products (FDA officials find credence in predictions of "a tremendous impact on health by 2010"), they must have multiple human trials under way by mid-decade.1 To assess trial readiness, we interviewed directors of clinical trial and medical informatics departments at our sample sites.
Academic Medical Centers Think They Are Ready to Run Clinical Trials
Interviewees believe that their institutions are generally prepared for pharmacogenomics. Sixty percent told us that their centers have an electronic medical record (EMR) in place — a must for managing phenotypic information for large numbers of patients —and 60 percent genotype patients in at least one department, as the following quotes illustrate:
"In our EMR right now we have all of the patient information, demographics, and clinical results transcribed and discrete. It covers every patient we see, and this year we'll have 160,000 outpatient visits alone....We already do genotyping for specific research studies. There's a good chance that by 2005 we'll genotype everyone who walks in the door."
But They Haven't Resolved Population-Access and Data-Protection Problems
Yet, when Forrester drilled down, we found concern lurking just below the confident surface. Our interviewees worried that the goal of patient privacy, which argues for keeping sensitive genomic information out of centralized databases, will be hard to reconcile with the goal of patient recruitment. For example, few patients have given written authorization for use of their medical records or tissue and fluid samples in clinical trials, which will complicate use of the samples following the enforcement date of the Health Information Portability and Accountability Act (HIPAA).
"I do not see genomic information being stored in a way that will allow people to search it for trial participants. Our institutional review board (IRB) will be very resistant.
"Some people have developed their own databases and recruit from them, but have never gotten patient permission to do so. After HIPAA, those databases will go away. Everything going forward will be okay, but the past stuff won't be consented."
AMCs' Management of Genomics-Related Information Is Badly Fragmented
Our interviewees described the decentralized management of genomics-related information technology as a major problem, since pharmacogenomics requires cross-analysis of patient phenotypes and genotypes (see Figure 1):
"There are no fields in my database for pharmacogenomics information. Even if someone asked me to add them, I would say no. That type of information is too complex for our clinical database."
"The problem is that we're inconsistent at this point. A few programs are doing genotyping and are capturing the information. These few programs are storing the data in separate program-specific databases. Not every program has one, though."
Interview Conclusions
From our interviews with directors of clinical trial and medical informatics departments at 20 leading academic medical centers, we learned that:
- These leaders want their institutions to be part of pharmacogenomics efforts
and believe them to be generally well-positioned to conduct the clinical trials
needed.
- When pressed, our interviewees describe problems securing relationships with potential trial subjects, matching up clinical and genotypic data on the individual patient, and organizing institution-wide information on multiple patients.
Analysis
Pharma Must Invest in AMCs to Get Genomics Trials Done
Why, despite loss of trial market share in the '90s, are AMC sites crucial to drug firms? Because neither providers of specialized expertise, such as independent labs that do genotyping, nor commercial patient recruiters, like site management organizations (SMOs), have the scope needed to support large numbers of clinical trials involving pharmacogenomics. Still, due to lack of preparation, we expect only a handful of AMCs to be ready by mid-decade, and these few are going to need industry help. To get trials under way, drug firms will have to find AMCs with which they can collaborate on building nine key capacities, all of them aspects of community ties, advanced IT, and strategic consensus (see Figure 2):
- Community ties: Given the importance of heredity in tracing pharmacogenomics
effects, trial recruitment will improve with AMC ability to engender trust
and sustain long-term ties with multiple generations of people in the same
locality.
- Advanced IT: The capacity to generate, store, and analyze data
will be key to understanding whether a drug's effect, a phenotypic response,
relates to the patient's genotype.
- Strategic consensus: No AMC will bring together the necessary elements of pharmacogenomics trial capacity by accident. Power centers within the institution will have to support investigator cooperation with pharma.
Community Ties Encourage People to Volunteer for Trials
Patient recruitment delays are huge bottlenecks in the process of getting conventional drugs to market.2 In pharmacogenomics, the task is more complicated yet — volunteers must be genotyped to let firms determine whether they've found sufficient numbers of recruits for major genetic subgroups. Drug firms should ally with investigatory sites that:
Access Volumes of Subjects
Successful sites must connect with large populations to amass subgroups with the right phenotypes and genotypes, a requirement that favors AMCs with reputations for integrity and dominant geographic positions, like The Cleveland Clinic and M.D. Anderson Cancer Center in Houston. Drug firms should do more than funnel qualified leads from their own call center and Web-based programs; they should work AMCs into their current relationships with online recruiters such as Acurian, HopeLink, and Veritas Medicine.
Aggregate DNA
Few trial sites will be able to fill pharmacogenomics recruitment quotas on their own. AMCs in noncompeting markets will likely cooperate to aggregate tissue and fluid samples for genotyping and possible identification of subjects. They will work with firms like Ardais, which has assembled a pathology department consortium including Massachusetts' Beth Israel Deaconess Medical Center, North Carolina's Duke University Medical Center, and others.
Facilitate Consent
With HIPAA imminent and government attention focused on protecting subjects in clinical trials, consent emerges as a major managerial challenge for AMCs. Smart institutions will negotiate subject consent and protect privacy as a dynamic rather than a static process.3 AMCs should simplify the sheer logistics of the task by offering consent self-service online, a task First Genetic Trust provides as an outsourcer.
Advanced IT Enables the Large-Scale Analysis of Phenotype and Genotype
To do pharmacogenomics, AMCs must collect and analyze detailed clinical information and genotypic data on multiple trial subjects, an IT-intensive undertaking. Sites must:
Deepen Patient Medical Records
To suit the molecular sub-classification of disease integral to pharmacogenomics, coding schemes must be not only granular but also consistent within and across institutions. Today, most electronic medical records (EMRs) classify complex conditions like skin cancers under a single ICD-9 code. To ensure both detail and consistency, AMCs should embrace de facto standards such as SNOMED, whose granular coding is gaining traction with Ardais and EMR makers Cerner and GE Medical Systems.
Assemble Medical Histories
Sites should gather patient clinical data that goes back over time; to boost the predictive power of their models, they should gather the same information on extended families. Minnesota's Mayo Clinic, Wisconsin's Marshfield Clinic, and Iceland's deCODE genetics have access to stable rural populations, which eases the task of amassing family histories. deCODE adds an extra dimension; 15 staff people are culling through church records and local histories to build electronic genealogies on Iceland's entire population of 285,000, enabling genetic linkage analysis on a broad scale.
Capture Molecular Information
Making data on genotypes and single nucleotide polymorphisms (SNPs) useable in a drug application means satisfying 21 CFR Part 11, the FDA's regulations on electronic records. Costs of Affymetrix or Motorola biochips alone argue for outsourcing the process to specialists like Quest Diagnostics and LabCorp, or to the services arms of biotech firms such as Genome Therapeutics and Orchid BioSciences. As AMCs intertwine their business processes with outsourcers and deploy technology to commingle operations, the outsourcing benefits will mount.4
Standardize Queries for Heterogeneous Databases
AMCs must organize information on genotypes and SNPs to include alphanumeric text, graphics, and expression array images. Look for firms like Scimagix to build image databases that sit alongside existing clinical record systems and are subject to standardized queries. deCODE genetics will build three heterogeneous repositories — of patient phenotypes, genotypes, and genealogies — then add a middleware abstraction layer and querying capacity across all three, creating the capacity to do high-powered linkage and association studies.
Strategic Consensus Reconciles Clinical and Commercial Goals
Sated by the short-term glut of NIH funds and pressed by government technology mandates like HIPAA, many AMCs are letting long-term bio-IT planning slide. Smart institutions will decline to follow suit. Instead, they will:
Plot a central role for bio-IT
AMCs should fashion an approach that intertwines biotech and infotech; one that targets pharmacogenomics, assesses investigators' IT needs, deepens EMR capacity, and addresses database heterogeneity. Marshfield Clinic has kept computerized patient records since 1985 and done world-class genetics since the early '90s. Partners HealthCare System and Beth Israel Deaconess Medical Center, competing systems in Boston, have strong IT leaders working on genomics strategies. Many other AMCs lag behind.
Accommodate Pharma
Since many researchers prefer NIH-funded research to commercial clinical trials, AMCs that do justice to both will accrue competitive advantage. Mayo, despite its recent deal with IBM, is tentative about using biotech and infotech to advance commercial pharmacogenomics. University of Pennsylvania Medical Center and Robert Wood Johnson University Hospital are more open to working with industry and will reap the benefits.
Pharma Needs an Action Plan for Next-Generation Clinical Trials
To overhaul their development strategies and budgets, pharma execs should:
Draft Specs for Tripartite Partnerships with AMCs and IT Vendors
Requirements planning should begin with the nine elements listed above. Next will come considerations unique to each firm, such as therapeutic fit. The Mayo-IBM deal should evolve into a Mayo-IBM-Bristol-Myers Squibb deal, given Mayo's and BMS' common commitment to oncology. In light of a shared interest in heart disease, Merck should hitch up with The Cleveland Clinic and forge a deal on behalf of both with opportunity-hungry Hewlett-Packard.
Provide Breathing Space for Academic Freedom
To find partners within world-class medical institutions, drug firms must leave behind traditional drug industry terms around secrecy. When Novartis hired cardiologist Mark Fishman away from Partners HealthCare of Boston and relocated its worldwide research operations to nearby Cambridge, Fishman bargained hard to free up Novartis staff to attend meetings, publish findings, and collaborate readily with other scientists.5
Help Fund Advanced IT Within Partnering Medical Centers
Drug firms should partner with rivals to underwrite institution-wide IT for friendly AMCs, and then target favored labs within these institutions for individual investments that create competitive advantage. IT priorities include tools that facilitate consent and privacy, deepen medical records and family histories, and extend abstraction layers and querying tools over multiple databases.
What It Means
As pharmacogenomics weaken blockbuster drug economics, pharma will move from product to corporate branding.
Medical Ethicists Find Their Market
Since AMCs need volunteers, sick and well, to donate samples for genomics research, they will offer inducements. One acceptable quid pro quo is to run new diagnostic tests on samples as the tests become available. As samples see use for years, even generations, ethical quandaries will multiply around notification, disclosure, and public versus private interests. When an AMC doctor sees the child of a parent genotyped at the institution, does the doctor recommend a test because he knows about the parent? Does he disclose the reasoning behind the recommendation, compromising the parent's privacy? Medical ethicists will be in demand for both individual counseling and policymaking.
Welcome to Super Bowl XL at Pfizer Field
As pharmacogenomics replaces blockbuster economics with targeted product dynamics, firms will shift mass media spending from promoting individual products to boosting the corporate brand. Merck will associate itself with the full spectrum of products for the heart, while GlaxoSmithKline will address the four distinct respiratory diseases once known as asthma. Heinz Field, hold the ketchup; companies like Pfizer and Johnson & Johnson will soon flaunt stadium-naming rights of their own.
