Innovation in medicines

There are major changes afoot in the complex world of the regulation of medicines. The regulatory burden on
the innovation and production of new drugs
has galvanised regulatory authorities, the pharmaceutical industry, and governments
into proposing new ways of doing things.

At the extreme end of the spectrum, in the
UK a new Bill has been introduced in parliament to facilitate access to innovative treatments.
The new Bill, submitted by Chris Heaton-Harris
MP under the title Access to Medical Treatments (Innovation) Bill, is intended to provide for a database of innovative medical treatments, and encourage responsible innovation by doctors in relation to the carrying out of medical treatment.

A medical treatment for a condition is 'innovative' if it involves a departure from the existing range of accepted medical treatments
for that condition.

A key provision of the proposed Act will be
that a doctor carrying out an innovative treatment may not be held liable in negligence if they depart from the 'existing range of accepted medical treatments for a condition if the decision to do so is taken responsibly'.

Public health concerns

The problems and unintended consequences
of this proposed legislation are manifold, both from a public health and a legal perspective. Although there is a great need for earlier access to medicines, and for ways of making innovative and biologically effective drugs more economically sustainable for both government payers and patients, this is not the way to go.

The most difficult issue will be the lack of credible, objective, validated, and reproducible pharmacological non-clinical and clinical data
on the safety and efficacy of newly introduced medicinal products, which would otherwise have allowed a proper assessment of the benefit and risk to the patient. There are two key dimensions to this problem: legal and scientific.

Starting with the scientific criticism, the development of new drugs depends on assessing the appropriate benefit and risk from all the available data on the efficacy and safety of the product, both in the community and specifically in the population of patients who suffer from the disease for which the product has been indicated. This evaluation will depend on the toxicology, animal and clinical pharmacology, pharmacokinetic, and pharmacodynamic data, together with the results of all the clinical trials.

The current statutory regulatory framework in both Europe and the US precludes the public dissemination of much of these databases because of data exclusivity and marketing exclusivity clauses designed to protect intellectual property and ensure commercial returns on investment for proprietary new products.

The objectives of these ‘instruments’ are to incentivise and protect investment in innovation research and development by the pharma industry. Unfortunately, it may have the opposite effect by hindering scientific research into new products while increasing the risks of safety defects in such new products.

One of the fundamental principles of scientific research is unhindered access to data relating to the issues at hand – this requires transparency of data in related experiments, the unrestricted ability to analyse these data in an objective, unbiased way, and the ability to debate the utility, accuracy, and credibility of such data together with criticism of the conclusions. All these components are crucial requirements for the translation of the biological science into the development of a safe and effective new medicine.

Lack of access to data

Restricting access to these databases will
gravely jeopardise the development of new, more effective, and safer medicines in these and other therapeutic areas. Possibly more importantly, these restrictions on access to information will hinder basic research into urgent public health issues, such as the development of resistance to antibiotics, parasites, and so forth, and the need to develop new therapies for common infective diseases, such as gram-negative intestinal infections, malaria, TB, and polio.

The consequential legal, ethical, and jurisprudential issues that will result from such restrictions are also worrying. One of the key problems will be the evidence required to be adduced in any court proceedings regarding clinical negligence, liability for defective medicinal products, patent law, and competition law. The general issue affecting all these legal frameworks will be the judicial evaluation of the admissibility, credibility, and weight of evidence in cases where there is such restricted access to the fundamental pharmacological safety and efficacy data of related products in related therapeutic areas.

A good illustration of the legal, ethical, and scientific development problems which may arise when new drugs are being developed without full access to preceding scientific, clinical, and pharmacological data is that of the immunomodulatory drug TGN1412.

The administration of the new drug in its first human clinical study precipitated a 'cytokine storm', an exaggerated, life-threatening pharmacological response, in volunteers. Such an event had been recognised some ten years earlier in a pivotal clinical trial supporting the development of a similar drug, but unfortunately the results of this trial had not been published and the data had remained confidential to the company. TeGenero, the developer, had not been able to properly review the overall pharmacology and clinical experience of such immunomodulatory drugs, and this went some way to the company being unable to predict what doses might be unsafe.

We believe that abandoning the need for the formal objective assessment of the benefit-risk profile of new and innovative medicinal products will make it unlikely this Bill will pass into law.

There are several other regulatory schemes which allow patients early access to important new medicines. Such schemes are based on scientific, legal, and public health frameworks which have been soundly established and have stood the test of time. If followed, these largely abrogate the need for initiatives such as the Innovation Act.

But one issue which all new schemes have
still to solve is that of cost benefit. Many new biopharmaceutical medicines are extremely expensive to develop and are applicable to relatively few patients, and thus their cost can
be prohibitive. But such is their potential, for example, to cure several forms of cancer and to arrest the progress of debilitating illnesses such
as juvenile arthritis, that the development of strategies to make them affordable in a cost-limited NHS is a matter of urgency. SJ

Dr Peter Feldschreiber, pictured, is a barrister practising from 4 New Square and Professor Sir Alasdair Breckenridge is the former chairman of the Medicines and Healthcare Products Regulatory Agency (MHRA) and the Commission on Human Medicines