Call to disclose investment in clinical trials to combat high drug prices

Médecins Sans Frontières (MSF) has published itemised costs of a $36 million trial it conducted comparing different drug combinations for treating tuberculosis and wants others to follow suit, in a bid to foster transparency around the cost of clinical research.

It claims it is the first time detailed costs of an individual clinical trial have ever been shared publicly.

In a paper presented at a World Health Organisation conference in April, MSF says this exemplar demonstrates it is possible to collect precise data on costs, even when a study runs over a number of years and is staged in a number of countries. The charity has published the toolkit it developed to do this and is encouraging others to use it.

Estimates for full research and development costs for new drug development range from €40 million to €3.9 billion, and clinical trials are often the largest single cost in that process. Costs for phase II and phase III clinical are estimated between €4.7 million and €133 million.

Having more precise information about the cost of developing an individual product would inform governments and health care providers when negotiating reimbursement and access.

“If that’s the claim [on costs] that’s going to be made to back up high drug prices that restrict access, there needs to be some transparency so it can be scrutinised,” Roz Scourse, who was in charge of the MSF study, told Science|Business.

However, it is not possible to extrapolate from the costs of MSF’s tuberculosis trial, which assessed the comparative effectiveness of approved drugs, to the multiple stages of clinical development required to generate the safety and efficacy data needed to get regulatory approval for a novel drug.

Rather, MSF wanted to show that it is possible to publish a break-down of clinical trial costs to better inform discussions around drug prices and patient access.

Pharmaceutical companies publish overall R&D expenditure in their financial accounts, but the exact figures for individual products are a closely kept secret.

Generic versions of patented drugs

High prices that restrict access to HIV, hepatitis C and other drugs, is a common issue in low- and middle-income countries, but it is also increasingly recognised as a problem in Europe and other high-income regions, Scourse said.

It is also the case that since 2006 the Access to Medicines Foundation has been tracking efforts by the pharma industry to improve access. Its latest index published in 2022, found that companies are increasingly allowing generic versions of drugs that are still under patent to be manufactured for use in low- and middle-income countries.

Scouse said MSF’s example is important if clinical trials have been publicly funded. “If you’re using public funding, there should be accountability and transparency” she said. The hope is that if public and non-profit bodies start sharing their R&D costs, it will put pressure on industry to follow suit.

The MSF toolkit aims to support this by offering a standardised template for reporting clinical trial costs, with costs broken down into 27 categories, in a bid to make publication less burdensome.

The toolkit was partly developed to facilitate information sharing under the proposed US Pharmaceutical Research Transparency Act, which would require drug developers to publicly disclose detailed costs of clinical trials.

The bill would require the National Institutes of Health to set up a publicly available database, including details of the total and per patient cost of clinical trials, and different costs such as personnel and health care services. Pharma companies would also have to include R&D costs in their annual financial reporting.

In 2019, the World Health Assembly adopted a resolution urging WHO members to enhance transparency on patents, clinical trial results and other determinants of pricing. For Scourse, this was a “key turning point” in highlighting the issue.

Industry maintains that assessing R&D costs for individual medicines is challenging, as it doesn’t always account for the majority of projects which fail at various stages of clinical research.

“The research-based pharmaceutical industry’s business model is based on portfolio investments across a broad range of science and not on individual products,” Nathalie Moll, director general of the European Federation of Pharmaceutical Industries and Associations (EFPIA), told Science|Business.

Moll argues drug prices should not be based on costs, but on the value the drug brings to patients and societies. Setting prices based on costs was the standard approach in several European countries in the 1970s and 1980s, but was later abandoned, she noted.

“This method not only created controversies about the measurement of costs but was also inefficient: on the one hand, it discouraged companies from seeking to reduce costs and on the other hand it inadequately rewarded added therapeutic value, leading to price discrimination according to the location of R&D and manufacturing units.”

Rather than improving access to medicines, she believes increased transparency of R&D costs for individual drugs would risk the publication of “inaccurate and misleading information” while disincentivising innovation.

“Full transparency of R&D activities may expose an inventor unnecessarily, making their invention accessible to everyone and subject to replication,” she said.

EU proposal

The European Commission is bidding to increase transparency as part of its proposed reform to the EU’s pharmaceutical legislation. If approved, the text would require drug developers to disclose any direct public funding. The European Parliament wants to extend this obligation to include direct funding from non-profits, as well as indirect public support, such as access to medical facilities and staff.

No definition is given for direct funding, but it primarily refers to direct grants and contracts to develop products, said Dimitri Eynikel, EU policy adviser for MSF’s access campaign. MSF advocated for the inclusion of indirect funding such as tax breaks and the use of public research infrastructure, laboratories and hospitals. “There should be some monetary value attached to this, because it uses public money,” Eynikel said.

He believes this could be a “transformative proposal”, as long as the plan to publish the funding information on a publicly available website is retained in the final text, ensuring non-governmental organisations and academics can analyse the data.

The EU’s pharma reform has sparked intense debate about how to strike the right balance between incentivising innovation and improving access to medicines. But a lack of transparency on everything from R&D costs and clinical trial data, to intellectual property and prices, is standing in the way of informed decisions, Scourse said. “There’s so much we don’t know in the whole biomedical R&D ecosystem that I think it’s impossible to have sensible policy conversations.”

MSF is not the only organisation pushing for more openness. In 2016, a coalition of consumer, patient and public health organisations launched the European Alliance for Responsible R&D and Affordable Medicines, which promotes transparency in policymaking as well as for R&D costs, drug prices and clinical trial data.