Most New Drugs Show No Evidence of Added Benefit
Most new drugs entering the market, particularly medications for neurologic and psychiatric disorders, provide no additional benefit over and above the existing standard of care, new research suggests.
In a large study, investigators found that only 54 (25%) of the 216 new drugs entering the German market between 2011 and 2017 were judged to have a considerable, or major, added benefit.
For 16% of these new agents, this additional benefit was either minor or could not be quantified. In addition, for 58% of these medications there was no proof of added benefit vs standard of care in the approved patient population.
The field of psychiatry/neurology fared the worst with just one of 18 new drugs (6%) showing added benefit. New drugs for diabetes also performed badly with only four out of 24 (17%) showing extra value.
"It is not acceptable that physicians and patients don't understand if these new drugs have extra value or not," lead author Beate Wieseler, PhD, German Institute for Quality and Efficiency in Health Care in Cologne, told Medscape Medical News.
"We are suggesting that there should be a requirement at the point of approval to show an added benefit over standard of care. Approval should be dependent on this," she added.
The findings were published online July 10 in the British Medical Journal.
Need for Active Comparator Trials
The investigators note that almost all of these medications were approved by the European Medicines Agency for use throughout Europe.
"Thus our results also reflect the outcome of European drug development processes and policies," they write.
They suggest that the situation has come about because regulators still allow placebo-controlled studies even though health technology assessment bodies have long recommended active controlled trials, which provide more useful information.
Of the 125 drugs lacking data on added benefit in the analysis, 64 had no studies vs an active comparator.
For another 42 drugs, studies compared the drug with an active comparator — but the comparator was inappropriate for such reasons as off-label drug use or inappropriate dosing regimens. The remaining 19 new drugs were tested against an appropriate comparator (standard care) but did not show an advantage.
The investigators acknowledge the argument that drugs can be approved without showing "added benefit" data to allow speedy access to new products, with the promise of future comparative studies. However, they note, such promises are often never fulfilled.
"A critical and well known problem with post-marketing studies is they often do not happen.... Globally, regulators do little to sanction non-compliant companies," the researchers write.
"High levels of uncertainty about treatment benefit jeopardize quality care and impede decision making, particularly on highly priced drugs in economically strained situations," they add.
Demand for Robust Evidence
Regulators should demand "robust evidence from longer term and sufficiently large phase III randomised controlled trials to prove efficacy and safety, which in parallel could be used to collect data for health technology assessment," the researchers write.
They also call for a mandatory requirement to conduct active controlled trials.
The current initiative on legislation for health technology assessment in Europe is an opportunity to implement such requirements, they write.
The investigators also suggest that health policy makers need to take a more proactive approach in the drug development process.
"Rather than waiting for drug companies to decide what to develop, they could define the health system's needs and implement measures to ensure the development of the treatments required," they write, adding that this could include needs-oriented public-private partnerships and not-for-profit drug development.
The researcher add that the drug development process and policies in Europe are not sufficient.
"Combined action at EU and national levels is required to define public health goals and to revise the legal and regulatory framework, including introducing new drug development models, to meet these goals and focus on what should be the main priority in healthcare: the needs of patients," they conclude.
In response to the article, the Association of Research-Based Pharmaceutical Companies in Germany issued a statement pointing out that the assessment of additional benefit "is not an easy matter — there is not always a 'right' or 'wrong.'"
"Without additional benefit, in the language of the methodologists, usually means 'just as good as the comparative therapy.' And precisely these drugs play an important role in medicine as treatment alternatives," they write.
For example, if a drug is not tolerated, "it is important that another, equivalent drug can be prescribed. For indications such as epilepsy, every alternative therapy is needed," they add.
The Association of the British Pharmaceutical Industry (ABPI) also issued a statement in response to the article.
"The UK has robust measures in place to ensure that medicines and vaccines are both clinically and cost effective before they can be used in the NHS. A medicine that can't demonstrate value is unlikely to be recommended for use," Richard Torbett, the ABPI's executive director of Commercial Policy: UK & International, said in the statement.
"Often we find that studies making similar claims invariably take a very narrow view of what constitutes 'value' that ignores issues that are important to patients," he added.
For context, the National Institute of Health and Care Excellence in England "takes a rigorous look at evidence on both clinical and cost effectiveness in making recommendations to the NHS and it recommends over 80% as being value for money," Torbett said.
The study authors have disclosed no relevant financial relationships.
BMJ. 2019;366:l4340. Abstract