An analysis published in the British Medical Journal  claims clinical trials may not provide a reliable evidence base for the cost-effectiveness of preventive medicines, such as statins, in many medical practices, reported PharmaTimes.

Differences between randomized-controlled trials that are often “the ideal” and not “the real” world of actual clinical circumstances “raises the question of how well our most widely used preventive drugs work in real life,” said Teppo Järvinen, orthopedic resident in the University of Tampere’s Department of Orthopedic Surgery, and colleagues from Finland and Canada, in the article. 

Despite the arguments of cost-effectiveness surrounding preventive drugs such as statins, antihypertensives and bisphosphonates, there are “no valid data on [their] effectiveness, and particularly the cost-effectiveness, in usual clinical care,” Järvinen et al contend. “Despite this dearth of data, the majority of clinical guidelines and recommendations for preventive drugs rest on these claims.”

Patients are selected for randomized clinical trials “who are carefully diagnosed, have a carefully defined risk profile for the event being evaluated ... do not have other serious illnesses, and are likely to adhere to the treatment,” the authors wrote. “Also, the study treatment is prescribed by doctors who adhere to the study protocol and participants receive special attention from dedicated staff.”

On the other hand, the effectiveness of treatments in clinical practice, is influenced by at least five factors, they wrote: the clinical population treated, diagnostic accuracy, provider compliance, patient adherence and health-care service coverage.

For example, in a randomized trial, population characteristics (e.g., age, sex), “generally diverge considerably from that of the clinical population,” while in real life, patients typically take fewer than half of prescribed treatments, compared with the 90% compliance commonly seen in trials.

Järvinen and his colleagues pointed to a recent assessment of the external validity of published cost-effectiveness studies on selective COX-2 inhibitors for inflammatory conditions. It compared the data used in these studies (mostly from randomized trials) with observed clinical data.

The trial data suggested that the cost of avoiding one adverse gastrointestinal event by switching patients from conventional non-steroidal anti-inflammatory drugs to COX-2 inhibitors would be around $20,000. However, when the same analysis was conducted using the U.K.’s General Practice Research Database, that cost was five times greater—$104,000.

Using bisphosphonates to prevent hip fractures in older people, the authors noted that these drugs are as cost-effective as preventive therapies for hypercholesterolaemia or hypertension. Expert panels concluded the same based on estimates from post-hoc Markov economic models.

But Järvinen said the fundamental problem with these models is that the data showing the drug’s efficacy do not reflect clinical practice. “In essence, the models extend the highly specialized trial evidence on drug efficacy as if it were widely applicable in community practice.”

As such, the fracture risk-reduction data derived from specific randomized trials (e.g., 1-2% reductions in absolute risk) are “applied to a wide population largely irrespective of age, sex, co-morbidity, bone status or previous history of fracture.”

This, the authors said, “is a far cry from reality.” The evidence that bisphosphonates prevent hip fracture is actually “very limited,” with marked reductions seen in a restricted subpopulation of women aged 65-80 with osteoporosis or previous fractures.

By contrast, evidence is lacking for efficacy among the people most likely to have hip fracture, the authors said—those aged 80 and older and those living in nursing homes.

“And although osteoporosis is considered a predominantly female disease, about 40% of age-related fractures occur in elderly men,” Järvinen said. “We need to put an end to this kind of gaming of the system and start to advocate true comparative effectiveness research,” Järvinen and his colleagues wrote.

“All relevant parties (doctors, patients, patient advocacy groups, the drug industry and government regulatory bodies) should acknowledge that it is everyone’s responsibility to ensure that we have true cost-effectiveness data on all preventive health care before it is approved for wider use and reimbursed by the government. This responsibility should not fall on the drug industry alone.”