Gold Standards Remaining Gold Standards for Germany's HTA

Any clinical trialists hoping for a softening of insistence on randomized clinical trials in Germany will have been disappointed by declarations made on Monday by Beate Wieseler, head of the drug assessment department at the country's health technology agency, the Institute for Quality and Efficiency in Health Care (IQWiG). "We need comparative data comparing the new drug with the standard of care in a robust study design, which is a randomized controlled study," she told a webinar organized by the European Public Health Alliance in Brussels. This is essential, she said, to be able to judge whether a new drug has any added benefit over the therapeutic standard, to tell patients and physicians what they can expect from it, and to establish a fair price. "If we don't have comparative data, we can't answer these questions," she said. "Other types of study like single-arm studies are not robust data to answer them."

Her views do not align with those of many regulators and HTA bodies in Europe, which are experimenting with adaptive licensing and managed entry approaches that try to work round the challenge of evidence development on innovative medicines, particularly when they are destined for smaller populations. Granting conditional marketing authorizations linked to post-marketing reporting requirements is not a solution where evidence is incomplete, said Wieseler. "We have seen an increase in insufficient evidence," Wieseler said. "We would like to see the evidence we need for decision making at the point the drug enters the market, but our experience is it's not there at this point and we also don't get it fast in post-approval." IQWiG is not, it would appear, moving in the same direction as the UK's NICE, which is exploring managed access programs and real-world data collection already in its Cancer Drugs Fund, and is looking to expand the approach. The European Medicines Agency is also developing its Data Analysis and Real-World Interrogation Network (DARWIN) as a network of healthcare databases across the EU that can provide real world evidence;

Wieseler focused on the notorious difficulties in obtaining companies' compliance with post-marketing requirements, with promised studies often delayed, incomplete, or incapable of resolving the uncertainties that led to only a conditional authorization. Because of this, German legislation has been changed "as an act of self-defense," she said. Requests for post-market data collection can be backed up by restricting prescription to physicians who participate in data collection, and even by the threat of price decreases where uncertainties remain unresolved. And because low levels of compliance are often linked to the sheer cost of running further studies and data collection, Wieseler suggested that a mix of public and private-sector funding could ease those challenges: "In Germany we are spending about €40 billion per year for drugs alone, so we could have a tiny percentage of that to run publicly financed studies to really improve treatment for patients."

Her comments cannot be lightly dismissed. Wieseler is an important figure in the European pharmaceutical landscape, and IQWiG is one of the most influential HTA bodies anywhere. Germany is also by far Europe's biggest—and richest—drug market. So RCT is not going away anytime soon. Like gold, it is not easily transformed.