PharmExec Blog

Assessing the Value of Retrospective Studies: Real-World Data, Real-World Applications

by Sarah Ray

The value of retrospective studies cannot be overstated. Retrospective studies affect many healthcare sectors, including the pharmaceutical industry and general public health. Applying these studies provides clear advantages at different points of the product life-cycle. During drug development, these studies may help clinical teams propose adaptations or even a companion diagnostic tests to identify the patient populations most likely to benefit from a company’s experimental treatment. This early work may lead to shorter trials and faster approval rates. If a product is already on the market, retrospective studies may bolster sales by highlighting the drug’s efficacy or by identifying its potential for use in other indications. Beyond pharma, retrospective studies may also help global health organizations such as the World Health Organization (WHO) in their efforts to promote and support public health policies.

Deciphering Clinical Trial Outcomes through a Retrospective Lens

Retrospective studies can prove instrumental for pharma, research organizations and other institutions conducting clinical trials. During the drug development process, dedicated teams may leverage retrospective studies to help them design robust late-stage clinical trials. For example, Genentech designed and implemented a companion diagnostic for its Phase 3 onartuzumab (MetMAb) trial based on retrospective analysis of its Phase 2 findings. In its Phase 2 trials, MetMAb extended the progression-free survival period for patients with high levels of the MET protein receptor from 1.5 months to 2.9 months. Consequently, Genentech bolstered the efficacy of its ongoing Phase 3 trials by exclusively targeting patients with high MET levels — the individuals who are most likely to benefit from MetMAb.

Clinical teams may also use retrospective studies to identify additional applications for drugs already approved for at least one indication. In such instances, retrospective studies are especially useful given a company’s risk of failure in early- and late-stage trials. Bernstein analyst Tim Anderson estimates that companies’ Phase 2 success rates have declined from 34% (2003–2007) to 22% (2007–2011). He also estimates that Phase 3 rates have decreased from 70% to 65% during the same period.

In the wake of patent expiries — and the risks associated with traditional clinical trials — many companies are pitting the merits of traditional blockbuster drugs and niche products against each other. Outside of these models, companies may also shift their focus from targeting symptoms attributable to a specific disease state to addressing the disease pathway. In this manner, retrospective studies may help researchers identify multiple disease states that, based on similar mechanisms of action, a single type of medication can target.

One recent study serves as a perfect example of this analysis. Published earlier this year in the Journal of Clinical Oncology, the study demonstrated that anti-HER2 drugs — already used in breast cancer treatment — may be an effective treatment for other cancers. The retrospective analysis found that 1% to 2% of lung cancer patients—or several thousand U.S. lung cancer patients annually — had a mutation in their HER2 genes, much like those patients with breast cancer. Likewise, the study found that some lung cancer patients with a HER2 mutation also experienced benefits from taking anti-HER2 medications. The retrospective study found that lung cancer patients with a HER2 mutation experienced an average of 5.1 months of progression-free survival—double the rate of survival for patients who underwent chemotherapy alone. Following publication of this finding, study authors are working to develop additional prospective trials. Ideally, these trials will further validate the use of existing anti-HER2 medications as treatments for lung cancer patients, as well as for other cancers with HER2 mutations.

Tracking Real-World Data to Support Global Disease State Awareness

Retrospective analyses also have public health implications outside of the immediate pharmaceutical world. Recent studies following outbreaks of the Middle East Respiratory Syndrome (MERS) coronavirus in Saudi Arabia emphasize the value of retrospective studies from a public health perspective.

One study, published in The Lancet, shows that some experts are using statistics from the severe acute respiratory syndrome (SARS) virus to gauge the probable effects of MERS. Within the study, researchers calculated and compared the basic reproduction rate figures for SARS and MERS. These basic reproduction numbers depict how quickly a virus is transmitted from person to person. The higher the reproduction number, the more easily a disease spreads. At the height of its prevalence, SARS had a reproductive number of 3.0. To compare MERS to SARS, researchers examined data from the early stages of both diseases. So far, researchers estimate MERS’ reproductive number to fall between 0.60 and 0.69. By comparison, data from the early stages of SARS showed a reproductive number of 0.80.

MERS and SARS may have similar profiles. However, the rapid spread of SARS compared to the slower rate currently observed with MERS may have been promoted by crowded populations. In response to the MERS health concern, public health officials are working to identify and track the source of the MERS coronavirus before it mutates or rises to the notoriety of SARS.

To prevent MERS from escalating, the WHO, the Centers for Disease Control and Prevention (CDC) and Saudi Arabia’s Ministry of Health maintain a proactive stance. The WHO is tracking the ways individuals become infected. The CDC has issued precautions for travelers visiting areas of known outbreaks. In preparation for both this month’s Umrah and November’s Hajj, Saudi Arabia’s Ministry of Health has established a medical surveillance system that will screen visitors for symptoms.

Moving Forward: Expanded Use of Retrospective Studies May Create New Opportunities in Drug Development

Ultimately, retrospective studies serve a multitude of purposes. Studies that use previous disease data as benchmarks may help public health officials target and contain new viruses earlier. When applied by companies’ research and development teams, retrospective studies may help companies refine their trial specifications and decrease the duration of their clinical trials. Equally important, leveraging retrospective analyses may enhance research organizations’ and pharmaceutical companies’ efforts to identify and target similar pathways across multiple disease states. In doing so, retrospective studies may contribute to an expansion both in the numbers and types of drug therapies that will be available in the future.


Sarah Ray is a Research Analyst at Cutting Edge Information. Upon joining Cutting Edge Information, Sarah has conducted benchmarking research into many pharmaceutical business functions, including pharmacovigilance, clinical development, marketing and medical affairs. She can be reached at
sarah_ray@cuttingedgeinfo.com.

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