Appunti di Tecnologia del direzionamento e rilascio controllato dei farmaci - Salmaso

Summary: Analytical Methods

Cost-Minimization Analysis: This method assumes equal therapeutic outcomes for various treatments analyzed.

Cost-Effectiveness Analysis: This is the most common method, which evaluates costs in monetary terms in relation to clinical outcomes.

Cost-Utility Analysis: This method is used when adverse reactions are severe and measures outcomes in QALY (quality adjusted life).

Cost-Benefit Analysis: This method is more difficult and measures both benefits and costs in monetary terms.

Cost Minimization Analysis: This analysis compares two interventions, such as two therapies with the same efficiency, effectiveness, and tolerability. It determines which therapy costs less, considering only the costs of production or delivery that can be easily calculated. It does not consider costs of treatment failure, severe adverse drug reactions, drug monitoring, or other healthcare services.

Cost Effectiveness Analysis: In cases where the treatments are not equally effective and tolerable, this method considers not only the costs of production but also evaluates the

outcome of the therapies.

A therapy is a cost-effective strategy when the outcome is worth the cost relative to competing alternatives. We use this analysis when we have to compare 2 different therapies, and determinate how use the one or the other. Cost/effectiveness results can be expressed as: cost/treatment, cost/outcome and cost/life saved.

For the cost/outcomes we can consider:

Clinical marker can be: mm Hg blood pressure lowering, mg/dL of LDL lowering, or other useful indicator. This numerical data can be compared for 2 different treatments.

The worst scenario is the when we have a dominated treatment, the cost is the highest, but the treatment is less effective. The best scenario is when we have a dominates scenario, so the cost is the lowest but the treatment is the more effective, but is a very rare case.

So the scenario most common is the NE quadrant, the more costly (when the treatment is new) and the more effective, and we have to consider is the cost worth the effectiveness. So

In this case, the Cost/effectiveness analysis must be done, also with the SW quadrant.

We do the analysis, and the outcome will tell that Cost-effective is not the least expensive, it may be:

• Less expensive but the same effectiveness
• More expensive and more effective (if the extra benefits worth the cost in surplus)
• More expensive and less effective (if the extra benefit of competing therapy is not worth the extra cost)

The idea is to understand if the extra benefits obtained from the new treatment are worth the increase in cost. We use the equation below to analyze the costs:

Cost effective is not always cost saving. With cost saving, we define an intervention that has a lower total cost than an alternative intervention (may not have the same effect). With cost-effective, we define an intervention that is sufficiently effective relative to its total cost when compared with an alternative intervention, considering that they have about the same effect.

So the cost/effective is a global data.

It's considerate also the benefit gets from the patient. Example: New drug or new drug delivery system in NE or SW quadrant. Drug A is doxorubicin in liposome, and Drug B is just the doxorubicin. Drug A works better than Drug B, but Drug A is more costly than Drug B.

How much does it cost us to add one year of perfect health onto the life of our patient? We have to obtain a relevant improvement of the quality of life use drug A instead of drug B.

3 - Pharmaco-economics and Controlled Release Systems venerdì 9 novembre 2018 12:31

COST-UTILITY ANALYSIS

In this analysis we introduce the concept of quality of life, so not only the cost-effective data. It determines the cost of adding one year of perfect health to a patient's life treat with a new drug. The analysis is based on Incremental Cost-effectiveness Ratio (ICER), which is the amount of money spent to add one year of perfect health onto the life of our patient. It's a ratio of cost to effectiveness per year. Utility is another parameter, a

il nuovo trattamento ha dimostrato di avere un impatto positivo sulla qualità della vita dei pazienti. Il numero che stima la qualità della vita è chiamato Quality-adjusted life-year (QALY). Questo valore tiene conto del tempo trascorso in uno stato di salute ottimale, chiamato "utilità". Ad esempio, se un paziente trascorre 2 anni in uno stato di salute ottimale, il QALY sarà pari a 2. Le misure di qualità della vita possono essere generali o specifiche per una determinata malattia. Ad esempio, nel caso del cancro ai polmoni, si potrebbe misurare la capacità di respirare. L'utilizzo di forme di dosaggio a rilascio controllato può influenzare i costi e i benefici del trattamento rispetto ai farmaci standard. Queste forme di dosaggio hanno dimostrato di avere un miglior risultato dopo il trattamento rispetto ai farmaci tradizionali. In conclusione, il QALY è un parametro importante per valutare la qualità della vita associata a una malattia o a un trattamento. Il nuovo trattamento ha dimostrato di avere un impatto positivo sulla qualità della vita dei pazienti, rendendolo una scelta promettente per migliorare i risultati clinici.both haveside effects which reduce quality of life.
STANDARD OF CARE NEW TREATMENT
1 year of life prolongation 1,5 year of life prolongation
Utility(level of health) 0.65 Utility 0.5 due to side effects
QALY 0.65 QALY 0.75
The new treatment is expected to add 0.75 quality-adjusted life-years to our patient's life, so this new drug improved the healthiness of the patient even if it has more side effects.
ICER (incremental cost-effective ratio) is the single most important indicator of an intervention's cost-effectiveness. We can calculate this parameters taking to account the differential cost of the two treatments, divide the difference between effectiveness of treatments (QALY'S difference). 7
So following the previous example, for the standard of care the cost is 12k $, and for the new treatment is 15k $.
The resulting ICER is
The ICER is 30.000/QALY. This number express the amount of incremental cost per normalized effectiveness per year for the new therapy. It accounts also forI costi correlati agli effetti collaterali e al livello di qualità della vita del trattamento. È legittimo spendere questi soldi per migliorare la vita di un paziente per 1 anno? La scelta spetta al sistema sanitario del paese (ministro) e dipende da come la vita può essere migliorata e da quanto sia facile ottenere migliori condizioni di vita. Il nuovo trattamento costa alla sanità pubblica 30.000 $ per paziente. Di solito un trattamento al di sotto di 50.000 $/QALY viene considerato conveniente dal punto di vista economico e questo costo deve essere razionalizzato rispetto al PIL del paese, quindi ad esempio negli Stati Uniti può arrivare fino a 150.000 $/QALY. ANALISI COSTO-BENEFICIO Invece di parametrizzare i dati clinici, tutti i dati sono espressi in dollari. Non è molto utilizzato. I costi sono stati confrontati con i benefici monetari dell'intervento, quindi gli esiti devono essere convertiti in dollari. Questa analisi determina quando i benefici superano i costi. L'analisi del costo-utilità è il tipo di analisi più completo. In questa analisi tutti i costi sono espressi in dollari, l'unica cosa che

change are the unit use to parametrize the outcomes:

• VARIOUS (but equivalent in comparative groups) in COST MINIMIZATION
• NATURAL UNITS (life years, LDL, blood pressure) in COST EFFECTIVENESS
• QALY in COST UTILITY (the more complete)
• DOLLARS in COST BENEFIT

We have to simplify the data to obtain this analysis, so in many cases we do oversimplification (every disease is very complex), and in every study there's a kind of standard deviation, due to the different condition of the different patient, in fact some people tolerate less the drugs than other, patient do not remain in one health state, each individual experiences different quality of life, incurs different costs. ecc.

GUIDELINES OF PHARMACO-ECONOMICS STUDIES

1. Cost effectiveness depends on clinical effectiveness, if the drug is not clinically effective the analysis is not necessary.
2. Cost effectiveness is a relative phenomenon, all the studies is comparative.
3. Economic evaluations can quantify cost savings.

The best time to do pharmacoeconomic studies is during the phase II of clinical studies, to assess the pharmacoeconomic value of new drug product, saving time and money. It have much lower cost than a standalone pharmacoeconomic study. But some data must be collected when the drug is already in the market, such as the improvements of life duration, so standalone study must be done.

This study is useful to advocate new products before their arrival in the market, even if is only a preliminary study.

Controlled release dosage forms usually have higher costs and higher pharmacoeconomic value:

• Increase clinical effectiveness
• Lower total treatment costs
• Provide tailored release profile
• Allow for better compliance usually deriving from lower side effects

How much chemo drug goes to the tumor when somministred parentally? The quantity is under 1%, with drug

Delivery systems can help achieve a targeting efficiency of 5%. For highly toxic drugs, controlled release systems can be used to reduce the amount of circulating drug in the plasma.

Controlled release systems are not a cure-all for diseases; they must be designed taking into account the physiology of the target. If the system is not well-designed, it can be toxic to the body's detoxifying organs.

Classic administration routes include:

• Oral administration (about 70% of drug administration): However, drugs must be able to withstand the low stomach pH and undergo hepatic clearance and potential hepatic damage. After the first passage effect, the viability of the drug is around 10-20%, as the majority is metabolized.
• Intravenous/intramuscular administration: This route is used for drugs with a short half-life or biological drugs. It bypasses the first passage effect, resulting in a higher viability. However, the first passage effect cannot be eliminated.

If there is an alternative route available, it may have a lower first pass effect and degradation.

so the concentration is higher in the blood.

Alternative administration routes:

• Transdermal (through the intact skin), relevant also for macromolecule
• Transmucosal (mucosa of the mouth, intestine, nose, vagina)
• Transocular
• Transalveolar
• Implantable
• Injectable
• Needleless (micro needle, the arrived to the derma, there's no pain because in the derma there's no nociceptor)

We have to develop polymeric materials with specific features and dedicated technologies, and analyze toxicology of this new systems.

We need also new technologies to make this new materials.

FEATURES OF THE MOST POPULAR DRUG DELIVERY FORMS

TABLET

• Drug forms ingested orally enter the circulation passing through the liver, a large fraction of the drug is metabolized (and can generate liver issue)
• pH effects can influence extent of delivery