MILAN – With all the official and media attention given to the worldwide trade in illicit drugs, the public has at most a dim awareness of the serious problems affecting the production, testing, and sale of the legal kind: the medicines that we take to treat or cure everything from AIDS to Yellow Fever.

The development of new drugs is a complex and lengthy process. It starts with an idea and requires a wide range of skills to bring that idea to fruition: synthesis or extraction of more or less complicated molecules, proof of their therapeutic effect in cell cultures and animals, testing for toxicity, and clinical studies.

Along this path, many potential drugs are withdrawn, and even successfully tested drugs face the additional hurdle of regulatory approval. Finally, the drug reaches the market, where it must be followed closely, because many adverse reactions are detected only with a large number of patients and after years of use.

There are several thousand drugs currently on the market, with a worldwide value of about $3 trillion. But conditions in the drug market are far from optimal.

Ideally, drugs should have a favorable risk-benefit ratio. Compared with other drugs with the same indications, new drugs should be selected on the basis of their safety, effectiveness, and cost.

But the financial interests involved tend to distort the process by creating incentives to overestimate the benefits of new drugs, underestimate the risks, and, above all, boost prescriptions.

What can be done? First, new drugs should always offer added value – better efficacy, lower toxicity, or greater ease of treatment. Unfortunately, this is not required by current legislation in Europe, where only quality, efficacy, and safety must be demonstrated, without any need for comparative studies. There is therefore the risk that new drugs may in fact be worse than products already on the market.

New drugs are often tested against placebos or drugs that are not the best treatment available, the point being to demonstrate that the new drug is not inferior to any already on the market.

But it is ethically questionable to test a drug for "non-inferiority,” because patients are exposed to potential risks while contributing, in the best case, to the development of a drug that is no better than those already available.

Patients’ informed consent usually does not provide a clear description of a non-inferiority trial, and the lack of added value indicates that in many cases the development of a new drug is driven by commercial aims rather than patients’ needs.

Second, improvement of drug development requires more transparency from the regulatory bodies. At present, a new drug’s producer prepares the entire dossier presented to the regulatory authority for approval; in the interests of the public, at least one of the clinical trials should be carried out by an independent non-profit organization.

Moreover, only the regulators can examine the dossiers, which are highly confidential. It is unacceptable that patients participating voluntarily in clinical trials, and their representatives, have no right to see data that would not exist without them.

Third, better conditions for the approval of new drugs should be matched by better use of drugs, which requires better information for prescribers. Today, information provided by drug makers largely predominates over independent information.

As a result, certain drugs are used much more frequently than would be expected from their approved indications. This so-called "off-label” use is sustained by continuous propaganda aimed not only at doctors, but also directly at the public. 

Direct but shadowy information tends to lead to "disease mongering” – the creation of diseases in order to boost prescriptions.

For example, the concept of "pre-hypertension” could extend the use of anti-hypertensive drugs dramatically, because everybody’s blood pressure rises with age.

Likewise, the notion that blood cholesterol should be as low as possible clears a path to treating healthy people with anti-cholesteremic agents. Clearly, health authorities must take closer control of information by becoming more responsible for physicians’ continuous education.

If the conditions for drug approval and marketing become more severe, pharmaceutical companies will be forced to produce fewer me-too drugs and more products of clinical importance.

Requiring longer testing periods, and possibly extra resources, could be compensated by new drugs’ greater longevity on the market, and patent coverage could be extended.

Finally, incentives must be found to encourage pharmaceutical companies to develop drugs that fulfill the needs of patients still awaiting therapy.

There are more than 6,000 rare and neglected diseases – many in developing countries – that lack remedies. The challenge is how to produce new drugs that – because patients are too few or too poor – promise very limited returns.

A partnership between governments, non-profit research institutions, charities and pharmaceutical companies might be one way to clean up the approval process for new drugs.

If public awareness of the current problems stimulates politicians to find a solution that works, better drugs and better drug use will be achievable.

Silvio Garattini is Director of the Mario Negri Institute for Pharmacological Research in Milan.

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