Most of the so-called innovations of the pharmaceutical industry are without therapeutic relevance. They do not improve health care, even though marketing and sponsored opinion leaders may disagree. Only one purpose is reached: therapy becomes more expensive, and that is the only aim. Excessive material investments to gain higher returns and market shares undermine the quality and economic feasibility of the health care system, leading to higher dues for the national sickness funds. Counter-measures are needed.

Real therapeutic progress is rare. We estimate that there are at best not more than two interesting drugs per year in clinical medicine, but only one every second year in general practice. Such innovations need no advertising. They are easily recognized by industry-independent pharmaco-therapeutic expertise and promoted without financial investment. The same expertise allows to recognize marketing bluffs and to establish a "restricted list for pseudo-innovations".

The self-government of the German medical profession appears to be unable or unwilling to act due to the widespread corruption of medical opinion leaders. The executive federal committee formed by representatives of the medical profession and the statutory sickness funds are blocked by court order with regard to any activities to control the German drug market, since it has been sued by the pharmaceutical industry as an illegal syndicate, according to European law. This case has not been decided, yet, and therefore the committee cannot act on the establishment of a restricted list for pseudo-innovations. The activity of the German pharmaceutical industry is remarkable, abusing legal actions for their purpose. The reference price system established first in Germany and subsequently taken on by many European countries is being played down here: The annual savings for the statutory sickness funds have been reduced by the new reference price law from annually 650 million Euro to 325 million Euro to appease the complaining drug industry.

The ministry of health is responsible to protect the citizens from ever increasing deductions to their statutory sickness funds caused by useless expenditures for pseudo-innovative drugs. Economic forces won't help, since they will create rising costs due to the fact that the financial input of the industry will prevent the process of quality-dependent product elimination.

Pseudo-innovations undermine therapeutic quality

Preference of established standard drug regimens is not an indicator for unwillingness to follow scientific progress, but for therapeutic conscientiousness. Drugs with well documented, high levels of efficacy - usually no longer under patent protection and therefore low priced - may be lost, when they are replaced by promoted "innovations".

The clinical benefit of Antidiabetic drugs such as glibenclamide (EUGLUCON), insulin (HUMINSULIN) or metformin (GLUCOPHAGE) has recently been demonstrated by the UKPDS (United Kingdom Prospective Diabetes Study; a-t 1998; No. 10: 88-90). Now the industry starts to promote a large-scale switch to so-called innovations. Glimepiride (AMARYL; a-t 1977; No. 1: 2-3), available only for 5 years, leads today's market with more than 2 million prescriptions at 100 million Euro. Advertised grotesque statements such as "Physiologic, Harmonic" (1) stimulated sales. Repaglinide (NOVONORM) introduced late in 1998 is now costing more money than EUGLUCON, which is still the most prescribed (and most expensive) glibenclamide. The proven long-term benefits of glibenclamide have been effectively silenced by noisy marketing campaigns propagating marginal advantages of repaglinide such as more flexible food intake (a-t 1998; No. 11: 100-1).

Even more damaging are advertisements for the Glitazones which are pushed into the market by misleading statements such as "From the very beginning" pioglitazone (ACTOS). Glitazones including rosiglitazone (AVANDIA; a-t 2000; 31: 66-7) are only licensed as adjuvant therapy in diabetes mellitus type 2 due to insufficient efficacy (a-t 2000; 31: 103). Potential to prevent diabetic complications such as cardiovascular disease was not tested for and checked before marketing authorization. Therefore, safety and efficacy of glitazones have to be regarded as questionable in view of published evidence, in spite of the advertised "new dimension" (2) in diabetic therapy. Inacceptable effects under therapy are weight gain during treatment and reports of cardiac and vascular adverse events and damages (a-t 2000; 31: 66-7 and 2001; 32: 64).

The tendency to increasingly prescribe artificial (modified) insulins cannot be explained by therapeutic advantages. Marketing strategies including questionable statements by the German Diabetic Society (a-t 2000; 31: 37-8) succeeded in achieving the second highest prescription rate for insulin lispro (HUMALOG) within five years only. Artificial insulins such as lispro and glargin (LANTUS; a-t 2000; 31: 108) show an increased receptor affinity to insulin-like growth factor IGF 1 and may, therefore, induce proliferating diabetic retinopathy and promote cancer (a-t 1999; No. 6: 66) - an unnecessary pseudo-innovation with a Damocletian Sword effect.

Pseudo-innovative drugs without any additional therapeutic effectiveness and with insufficiently tested long-term safety can be found among many therapeutic classes, e.g. Alpha-adrenoceptor blocking agents, Calcium-channel blockers, Proton pump inhibitors, Thiazide diuretics, Loop diuretics etc. (Table). New chemical structures such as zolpidem (BIKALM; a-t 1996; No.7: 72) or Angiotensin-II receptor antagonists rapidly turn out to be nothing but another variation of a well known agent.

Angiotensin-II receptor antagonists were first marketed in 1995. In 2000, already 3.8 million prescription units (combination drugs excluded) were sold at 385 million Euro, as compared to 19.6 million prescription units of ACE-inhibitors at 640 million Euro. A therapeutic benefit has been proven regarding stroke prevention, cardiovascular events, and reduced mortality rates only for ACE-inhibitors, but not for the much more expensive angiotensin-II receptor antagonists (a-t 2001; 32: 2). Prolonged life expectancy has been demonstrated for patients with heart failure when treated with ACE-inhibitors, but not with angiotensin-II receptor antagonists (a-t 2000; 31: 68-9). Patients suffering from ACE-inhibitor induced or other angio-edema cannot be switched to angiotensin-II receptor antagonists (a-t 1998; No. 11: 105). However, the latter drugs may be an alternative for the 3% of patients suffering from severe cough with ACE-inhibitor therapy.

The antiplatelet agent clopidogrel (ISCOVER, PLAVIX) has no place in routine therapy and belongs to a rather limited niche of indications. Treatment with clopidogrel is more than 50 times more expensive than with ASS (ASPIRIN). Therefore, its use may only be justified in patients showing serious contraindications to ASS (a-t 1998; No. 8: 70-1). It is without any relevant therapeutic advantage over ASS in the secondary prophylaxis of stroke (a-t 2001; 32: 34). But it should replace its predecessor ticlopidine (TICLID), since it appears to be less toxic to bone marrow.

Administrative aspects

Legislative measures for introducing a restricted list for pseudo-innovative drugs are not new to the German Social System. Laws already exist:

• The demand for economic guidance of medical treatment is instituted within social legislature (Sozialgesetzbuch V) as well as a legal basis for a restricted list of drugs (§ 34 SGB V).
• The law on reference pricing allows to fix the drug price for alternatives paid by the statutory sickness funds within the lower third of the price-range between lowest and highest product price.

Possible savings

Examples shown in the table (for the year 2000) indicate that expenditures for drugs can be reduced by about 1.5 billion Euro if prescriptions are switched to proved alternative drugs of proven efficacy. This will also improve the quality of medical care for patients.

Professor U. SCHWABE presented similar figures at the Hearing of the Deutsche Bundestag on legislation concerning the medication budget for doctors working for the statutory sickness funds. He calculated that the expenditures for drugs financed by statutory sickness funds amounted to about 20 billion Euro in the year 2000 and that about 1.25 billion Euro can be saved by abandoning prescriptions of pseudo-innovative drugs ("analogues"). (3) Switching prescriptions completely to generic products will save an other 1.5 billion Euro. (4) Therefore, expenditures for drugs can be reduced by more than 2.5 billion Euro or 13% of the total medication expenditures of the German statutory sickness funds. This money could be used as a refund to members of health insurance programs or for substantially innovative treatments without increasing health care costs for the patients.

Conclusions

The intended reform of the German health care system should try to control the abundance of useless new drugs with questionable potential by extending the restriction list to pseudo-innovations.

	Pseudo-innovations impede therapeutic progress by consuming the financial means needed to finance sound therapeutic advances.
	The establishment of a restriction list for pseudo-innovations combined with generic prescribing will activate a reserve of more than 2.5 billion Euro without affecting the quality of health care.
	Quality and safety of drug treatment will improve by focussing on established therapeutic principles and avoidance of less thoroughly tested "new" drugs.
	These savings spare the public from increasing insurance premiums and the medical profession from claims for compensation.

1

Hoechst: AMARYL-advertisement, Ärzte-Zeitung, Nov. 25, 1996

2

SK BEECHAM: Advertisement for AVANDIA, Ärzte-Zeitung, July 20, 2000

3

SCHWABE, U: Deutscher Bundestag - 14. Wahlperiode - 101. Sitzung, Gesundheitsausschuss, 27.06.2001

4

SCHWABE, U. in SCHWABE, U., PAFFRATH, D. (Hrsg.): "Arzneiverordnungs-Report 2000", Springer, Berlin 2001, p 687-713.