REVIEW ARTICLE : EFFICACY OF ONCOLOGIC DRUG THERAPY: A MANAGEMENT TASK IN FUTURE HEALTHCARE

Author m luisetto PHARM D , HOSPITAL PHARMACIST MANAGER , APPLIED PHARMACOLOGIST,EUROPEAN SPECIALIST IN LAB. MEDICINE maurolu65@gmail.com Italy 29122

keywords . MANAGEMENT OF THE SYSTEMS, COST CONTAINEMNT, BUDGET ANALISYS , oncology therapy, real efficacy, clinical trial , improvement of clinical outcomes ,clinical pharmacy , pharmaceutical care , new drug therapy

introduction

In actual international economic cycle a rational use of drugs and medical device has become a real priority in order to correctly use the limited econonomic resource today available and the cost for cancer treatment are increasing in logarithmic way in last decades related to the introduction in therapy of new option as pharmacological therapy.

healthcare government and public or private institutions ,insurance company and other subject are involved in high costs management much more than past ( in example cost for drugs , medical devices and , new diagnostic procedure ).

Healthcare managers ask to the clinical pharmacist professionals to rationalize costs in example involved in new innovative therapy, due to medical therapy errors and also in order to have an efficient logistic systems ( hospital pharmacy ) .

For this reason Clinical pharmacist every day work in healthcare setting are strongly applied to monitoring high costs related to diagnostics procedures and drug therapies .

Cancer imply diagnostic systems ( med lab, imaging , molecula biology , genetic analisys) and therapy need

To correctly classify the neoplasia ( phenotype, resitence et. Other ) in order to have a more efficacy therapy. ( every stage of this process imply hig costs )

We can see patien treated with classic chemiotherapy or biological alone or combined and new tretement are increasing today ( also the costs involved )

The economic aspect are relevant on cost of drugs and payment by government and institution or insurance.( in example 30-40.000 euro/USD/ patient for some new innovative biological MABS )

Even ministry of health in some countries ( in ex. ITALY ) not pay all some new innovative anticancer drugs but use a system that verify the results obtained.( payment by results, risk sharing et other procedure ).

But Clinical pharmacists professional need to have management intruments to be added to their classic university core curriculum .( knowledge and practice applications)

A rational use of clinical pharmacists human resource is a golden endpoint in every settings with the change from logistic to more clinical Function ( clinical pharmaceutical care new healthcare discipline

( luisetto, s.rahu 2016 ukjpb).

“Extremely complex health care organizations, by their structure and organization, operate in a constantly changing business environment, and such situation implies and requires complex and demanding health management. Therefore, in order to manage health organizations in a competent manner, health managers must possess various managerial skills and be familiar with problems in health care. Research, identification, analysis, and assessment of health management education and training needs are basic preconditions for the development and implementation of adequate programs to meet those needs……………. The need for knowledge of certain areas in health management, as well as the need for mastering concrete managerial competencies has been recognized as top-priorities requiring additional improvement and upgrading.” Osman Slipicevic and Izet Masic

“Although management practices are recognized as important factors in improving health care quality and efficiency, most research thus far has focused on individual practices, ignoring or underspecifying the contexts within which these practices are operating. Research from other industries, which has increasingly focused on systems rather than individual practices, has yielded results that may benefit health services management.

Our goal was to develop a conceptual model on the basis of prior research from health care as well as other industries that could be used to inform important contextual considerations within health care.

……………………we reviewed relevant research from peer-reviewed and other industry-relevant sources to inform our model.

The model we developed was then reviewed with a panel of practitioners, including experts in quality and human resource management, to assess the applicability of the model to health care settings.

The resulting conceptual model identified four practice bundles, comprising 14 management practices as well as nine factors influencing adoption and perceived sustainability of these practices. The mechanisms by which these practices influence care outcomes are illustrated using the example of hospital-acquired infections. In addition, limitations of the current evidence base are discussed, and an agenda for future research in health care settings is outlined.

Results may help practitioners better conceptualize management practices as part of a broader system of work practices. This may, in turn, help practitioners to prioritize management improvement efforts more systematically.” .Garman AN1, McAlearney AS, Harrison MI, Song PH, McHugh M.

healthcare management today more than past need strong condition in using drugs resource in oncology filed. Cancer is so diffused and elderly people is increasing in modern society.

But as clinical pharmacist we can discuss some problem in relationship between efficiacy of the actual therapy and the cost involved. :

Every medical speciality has disease treated with high or medium or low results so in the same way we can have drugs with different profile of efficacy . We can easy observe that many disease have efficacy drug therapy , often only 1 drug resolve the pathological condition.

In order to have more clinical results are used association ( in example one of the first used was Sulfametoxazole –trimetroprim in antimicrobioal filed ) But in many disease even associating 2-3-4 drugs the % of cure of a disesase not increase.

What it mean? In example we can see In many oncologic disease or in methabolic disorder ( as type 2 diabetes ) are currently used association in order to improve clinical outcome .

It mean that this drugs are not the best? Or low active ?

Why for this pathological condition drugs not do the right works?

There is the need for new really efficacy drugs that show a profile of efficacy as requested in order to resolve the patological condition?

Is etichal to approve and register new oncological drugs that demonstred 1-2 month pus in svurviving ? is etichal that public institution pay for drugs that increase only few month surviving ?

There are medical procedure currently used in healthcare that have 100% of efficacy( for example in sterilization of medical devices or parenteral drugs) but we have registered a lot of drugs with high variable profile of activity.

Other drugs show real efficacy in example : acetil salicylic acid in anti aggregant properties.

The same morfin has its own analgesic property and often not need to be associate to other Drug classes to have a good level of activity .

The same for cloranfenicol :we know its efficacy even if we know well its toxicity .

Statin in lowering cholesterol, thiopental in ICU, eparin ad many others example as insulin , some antidotes, some ananestetic or muscolrelaxant molecules.

In neuropsychiatric disese drugs show a variety of efficacy and a great placebo effect. (in some cases about 30%).

In some condition we can see for example in the treatment of tipe II diabetes we see a great use in politerapy , association are commonly used in antimicrobial therapy in MDR resistance and other factors.

In example clavulanic acid as enzymatic inhibitor associate to amoxiciiliin and other drugs used for TBC infections( triple therapy ) or for HIV to reduce resistence.

But also in oncologic field we can see a great use of multidrug therapy ( even if there are neoplasia with great response to drugs in other we do not have a good response ) .

What is the meaning of this situation? We have today the right efficacy drugs? Or we have to think to a new generation of drugs that prove real and relevant clinical efficacy to be used whit real usefull results ?

Wy we have today sophisticated biological agents registrated that gives only few month in surviving in oncologic field ?

Is the right strategy to use the today limited economic resource ? is really the best think to registered drugs that gives only few increase or not relevant in mortality rate or other hard enpoint?

Why are commonly used today some drugs that present high level of resistence (for example that simply use different intracellular seconde messager) ?

This situation easily give resistance.

Why is used to poison the cell whit some intracellular oncology drugs when is known that the cell naturally extrude poison from it s inside as a natural defence mechanism?

The introduction of novel delivery systems that make possible to bypass this problem can give more clinical results. ( ERLICH MAGIC BULLET THEORY ).

The classic chemioterapic drugs must acts in cancer cell in priority way and new delivery systems can do it in better way.

The cancer cell during its life has different and progressive mutation and in some cases the drugs used give mutation itself.

In some cancer as pancreas , liver , brain, gastric the response to chemitherapic is not at level of treatement of other ( in example LMC ) and this is a real keypoint to rethink the problem.

Ematologic cancer have a different profile in drugs response vs solid tumors.

We can not use the term healing in ongology field in light way .

Because reactivation of disease we can have after also many years and clinical healing can not be a molecular complete response.

It is easy to think that The cronic patients are more interesting vs a get better one ( can be a pharmaceutical industries view).

In the last decades we have seen a progressive improvement of anticancer therapy using different strategies as association of chemitherapics, tirosin kinase inibithors, mabs , radiodrugs and other .

Cycle OF CHEMIOTHERAPY associated to mabs can attack the cancer cell in different stages or with different mechanism.

Continious infusion of some chemitherapic drugs increase activity in example. ( cell are in different cycle).

Using cycle strategy toxicity can be contained and efficacy improved.

Clearly the efficacy of the chemiterapic drug therapy is related to the stage of the disease ( local or diffused as methastatic) and the strategy change a lot adding this pharmacological therapy to surgery, o radiotherapy .

If classic chemitoherapic drugs are associated with different level of toxicity using mabs we have not this kind of problems and the possibility to treat also elderly patient or in severe conditions.

The knowledge in genetic profile, mutation level can gives the right therapy application and not using towards patient for example genetically resistence.

Mutation , genetic instability and other condition can heavly influence the drug therapy response.

The increase of clone resistance is easily in tumor destiny.

The presence of sanctuary for metastatic cell contribute to the evolution of the patology .

Other tumor can be kinetically resistance because high part of the cell remain in a cycle fase characterized by low rate of development.( for this reason the association of differente drugs with different profile of action gives more result s vs monotherapy )

Other causes of resitence can be :

Reduced permability of the cancer cell to the chemitherapic drugs.

Augmented methabolism of the drugs

Augmented extrusion fron cell inside ( extrusion pump ) gp-170

Enzyme level augmented in response to the inhibitor dugs used.anternatives pathways

Enzymatic deficit due to the drug acitivity

Gene amplification

Alterated methabolism , augmented inactivation , alterated Dna reparation system

Target modify , receptor internalization

Alternative surway mechanism

Drug intake modified

Lower cellular intake of drugs

Anti apoptotic mechanism

Pleyotropic resitence ( towards differet class of molecules )

MDR

And other relevant mechanism (knowed and unknowed)

Classic chemiotherapic drugs present high toxicity bus vs mabs show less resistence linked to the direct toxicity

However Only few mabs show a real efficacy ( HERCEPTIN RITUXIMA CETUXIMAB BEVACIZUMAB and few other ) and many present resistance profile.

We have few mabs in first line vs classic chemiotherapic drugs association

Using nanotecnologies we can lead classic drugs into the only cancer cell bypassing the resistence in example in mabs therapy .

But thinking at the actual situation : We need new rules for registrative clinical trial?

And Why if is demonstrated the with clinical pharmacist in medical team we have general improvement in clinical outcome is not officially required this presence in registrative clinical trial?

The decision making systems in cancer therapy must consider the clinical pharmacist presence in the medical team to improve clinical otcomes :

“Every drugs is registered for specifically indication, at the same time every

drug to be a rational therapy need a rational decision making system

that require a multidisciplinary team that can cover all aspect of

pharmaceutical molecular metabolism kinetics and

pharmacodynamics this create great possibility for clinical pharmacist

but it must increase expertise in field of diagnostic (lab medicine and

imaging) for the high relationship whit drug therapy.) ”editorial an useful instrument in future healthcare j. ph. Care and health m luisetto 2016

and an other question is :

“is request clinical pharmacist presence in clinical trial for drug registrative use? If the pharmacist presence in medical team gives improving in some clinical outcomes why is not request by regulatory clinical pharmacist presence in registrative trial?” m luisetto editorial 2016 An Useful Instrument in Future Health Care Systems int journal of ph. Care and health systems omics

in clinical trials are today used vs gold standard PFS progression free survival , overall survival , TTP, TTF, EFS, , TTNT , ORR, DOR to compare activity .

MATERIALS AND METHODS :

We observed some pubblication in biomedical database involved in ancticancer therapy or in registrative procedure in order to evaluate the actual situation.

The same we observe :

the profile of efficacy of actual therapy and related costs related to last guideline .

some article involved in healthcare management

Results : (1-20 )

Vinay Prasad, in jama oncology Five Years of Cancer Drug ApprovalsInnovation, Efficacy, and Costs Sham Mailankody, MB BS1 writed :

“The price of cancer drugs has risen, drawing criticism from leading academics.1,2 The annual cost of a new cancer medication now routinely exceeds $100 000, and medical bills have become the single largest cause of personal bankruptcy.2 Although some contend that the high cost of drugs is required to support research and development efforts,3 the fact remains that when costs and revenues are balanced, the pharmaceutical industry generates high profit margins.4

High profits may be justified if novel products offer significant benefits to patients (thus producing indirect economic value through the patients’ restored health) or if they represent significant pharmacologic advances over their predecessors—offering new mechanisms of actions and emblematic of high-risk research. We investigated whether novelty of medications or their relative benefits affected drug pricing.

Cancer drug prices are rising faster than the prices in other sectors of health care, drawing concern from patients, physicians, and policy researchers.5,6 We found little difference in the median wholesale price of 21 novel drugs and 30 next-in-class drugs approved over a 5-year period (next-in-class drugs, $119 765; novel drugs, $116 100; P = .42). Our results suggest that the price of cancer drugs is independent of novelty. Additionally, we found little difference in price among drugs approved based on time-to-event end points and drugs approved on the basis of RR. Our results suggest that current pricing models are not rational but simply reflect what the market will bear.”

• 2015 Pharmacist Cognitive Service and Pharmaceutical Care: Today and Tomorrow Outlook, M. Luisetto, F.Carini, G. Bologna, B. Nili-Ahmadabadi, UKJPB UK Journal of Pharmaceutical and Biosciences Vol. 3(6), 67-72, 2015 , in this study was observed general improvement in some clinical otucomes when clinical pharmacist take really part of medical team.

• J Immunother. 2015 Sep;38(7):259-66. Statistical Considerations in Clinical Trial Design of Immunotherapeutic Cancer Agents. Dranitsaris G et al

The classical model for identification and clinical development of anticancer agents was based on small molecules, which were often quite toxic. The decision to take the drug into the randomized phase III clinical setting was usually based on the proportion and duration of objective tumor responses, along with overall survival compared with historical controls.

Immune-oncologics that are designed to fight cancer by direct CD8(+) T-cell priming and activation or by blocking a negative regulatory molecule have a number of sharp distinctions from cytotoxic drugs.

These include cytoreductive effects that may be very different in timing of onset from traditional chemotherapy and the potential for inducing long-term durable remissions even in heavily pretreated patients with metastatic disease.

In this paper we review the different classes of immune-oncologic drugs in clinical development with particular attention to the biostatistical challenges associated with evaluating efficacy in clinical trials. Confronting these issues upfront is particularly important given the rapidly expanding number of clinical trials with both monotherapy and combination trials in immunooncology

• Z Evid Fortbild Qual Gesundhwes. 2013;107(2):120-8. Epub 2013 Apr 4. [Cancer: Is it really so different? Particularities of oncologic drugs from the perspective of the pharmaceutical regulatory agency].Enzmann H1, Broich K.

As with other medical drugs, the marketing authorization decision is based on the assessment of its efficacy, safety and pharmaceutical quality but does not consider price or reimbursement. More sophisticated diagnostic methods drive an increasing stratification of cancer into a multitude of different diseases. Regardless of their different pathogenesis and therapeutic options the most relevant clinical endpoints remain cure, overall survival and progression free survival. These endpoints include both efficacy and safety, as patient survival reflects the sum of the beneficial anti-tumour effects (increasing survival) AND the adverse effects (decreasing survival). The benefit of an anticancer medicine should be evident from both overall survival and progression free survival (e.g. used as primary and secondary endpoints). Mature data on overall survival may not be needed for marketing authorisation if a clear increase in progression free survival convincingly predicts a beneficial effect on overall survival. In these exceptional cases treatment of patients with an obviously beneficial medicine must not be delayed - possibly for years - until the exact size of the benefit has been established.

Conditional approval and approval under exceptional circumstances may accelerate patients' access to a new medicine.

Both postulate that the extent of the benefit cannot be determined with sufficient certainty at the time of marketing authorisation.

This uncertainty may have a negative impact on price and reimbursement as these decisions may consider data or assessments from the marketing authorisation procedure. Therefore, marketing authorisation applications and subsequent pricing and reimbursement negotiations should not be regarded as completely independent processes, but be included in an overall strategy for the development of oncologic drugs.

• Cancer Res Treat. 2012 Mar;44(1):1-10. Epub 2012 Mar 31.

Present status and problems on molecular targeted therapy of cancer. Saijo N1. Oncology (Williston Park). 2006 May;20(6 Suppl 5):10-8.

Cancer Res Treat. 2012 Mar;44(1):1-10. doi: 10.4143/crt.2012.44.1.1. Epub 2012 Mar 31.

Present status and problems on molecular targeted therapy of cancer.Saijo N1.

Numerous clinical trials of molecular targeted drugs for cancer have been conducted, with remarkable results for certain drugs and accumulation of "negative data" causing a hitch in the development plan for some other compounds. Drug discovery and effects against driver mutations (activating mutations) and problems: possibility for circumventing inherent and acquired resistance with the aim of achieving radical cure. Synthetic lethality: reasonable patient selection in individualized treatment strategy. Response rate and progression-free survival improvement with or without overall survival benefit and enhancement of toxicity in bevacizumab therapy: best endpoints for the evaluation of effect of antiangiogenic therapy. Negative data on small-molecule targeted therapy, primarily vascular endothelial growth factor tyrosine kinase inhibitors: loose GO or NO-GO decision criteria for further development of new compounds in early clinical trials. Effect of immunotherapy: difficulty to verify by proof of principle study. We are faced to many questions for the development of efficient personalized therapy. Accumulation of scientific global preclinical and clinical evidences is essential to use these new therapeutic modalities for the improvement of oncologic health care.

Historic evidence and future directions in clinical trial therapy of solid tumors.Gollob JA1, Bonomi P.

Although improved survival is the "gold standard" for proving clinical benefit of oncologic therapy, the U.S. Food and Drug Administration (FDA) has accepted significant results in clinical trials using surrogate endpoints as the basis for drug approval. One surrogate is the amount of tumor reduction, or tumor response.

Moreover, tumor response may not be an appropriate endpoint for evaluating the effects of the new targeted therapies, whose putative mechanisms are generally cytostatic rather than cytotoxic. Clinical trials suggest that some patients with other solid tumors, such as lung cancer, may derive clinical benefit from treatment that helps stabilize their disease. There is also controversy as to whether the Response Evaluation Criteria in Solid Tumors (RECIST) provides the most appropriate instrument for assessing tumor burden. Ultimately, use of a variety of endpoints as well as different trial designs may provide an adequate basis for investigating the benefits/risks of newer therapies.

Daniel Sargent in What Constitutes Reasonable Evidence of Efficacy and Effectiveness to Guide Oncology Treatment Decisions? Writed :

“ The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

The need to practice evidence-based medicine is the current prevailing paradigm within the medical community. Evidence to guide practice can and should come from a variety of sources, including clinical trials, observational studies, and meta-analyses of both or either. This paper discusses the relative strengths and weaknesses of data that arise from these various sources. The different types of evidence required to demonstrate “efficacy” versus “effectiveness,” a critical and often overlooked distinction, are discussed. In the genomic age, in which targeted therapies with or without specific biomarkers are emerging in cancer care, new approaches are necessary to generate the evidence required for decision making.

Conclusions

The practice of evidence-based medicare requires the use of careful and disciplined methodologies to provide reliable information to guide clinical practice. Whenever possible, randomized data are clearly preferred to results based on nonrandomized trials. In the presence of bias, large sample sizes are of little benefit, and in fact may only make us more confident in the “wrong” answer. Pragmatic and/or cluster randomized trials may provide a critical link between the highly regulated “efficacy studies” that dominate current oncology research and the “effectiveness” studies that are critical to clinical practice. The establishment and validation of personalized medicine require further innovation in these areas. The need for innovative methods in oncology research is readily apparent; successful development and implementation of such methods will allow the generation of reliable evidence to guide the future of cancer care.”

Mustaqeem Siddiquia and S. Vincent Rajkumarb in 2012 writed “Last year, ipilimumab (Yervoy; Bristol-Myers Squibb, New York, NY) was approved by the Food and Drug Administration (FDA) for the treatment of metastatic melanoma. The benefit in survival over and above standard treatment arms was 3.7 months in previously treated patients and 2.1 months in previously untreated patients.1,2 The cost: $120,000 for 4 doses. As staggering a figure as that is, the drug is hardly alone in its lofty price. We believe that the immense cost of contemporary cancer drugs signals even greater costs for future drugs (Table).

Cost of Selected Drugs Used in Cancer Therapya

In health care delivery systems in which third-party payers (private or government) cover the costs of cancer treatment and the insured public has a presumed and possibly legal right of access to all approved drugs, the soaring price of cancer drugs poses at least 3 major problems. First, the absolute cost to society will become increasingly unaffordable if every drug with statistically significant but clinically unimportant benefit is approved. Second, it becomes problematic for insurance companies to price policy premiums

accurately3 because the approval, clinical acceptance, and incorporation of expensive new drugs is unpredictable and geographically variable. As a result, insurance premiums need to be meaningfully increased to keep up with the cost of care. Third, almost all approved cancer drugs are eventually used for conditions and settings not approved by the FDA (ie, off-label use).4,5 The data to support these indications are almost always much less rigorous than those used to gain FDA approval. Off-label use may increase expenditures on a drug that offers little or no efficacy.

For patients treated for cancer, the median out-of-pocket expenditure for patients with private insurance was approximately $1500 in 2003 to 2004, with 25% of patients spending slightly more than $5000. According to The Henry J. Kaiser Family Foundation, the median income (including social security, pensions, and other earnings) of Medicare beneficiaries is less than $22,000.6 This fact raises serious questions as to how Medicare beneficiaries will be able to bear the increasing burden of health care costs. Indeed, the percentage of personal bankruptcies in the United States attributed to health care costs rose from 46.2% in 2001 to 69.1% in 2007.7 More concerning, health care reform in Massachusetts (the template for national health care reform) did not seem to decrease the percentage of personal bankruptcies due to health care costs.8 As serious as the problems are in the United States, there are additional issues in less wealthy countries, where resources are considerably constrained. With a much lower median income, the proportion of expenditures directly paid by the patient is much higher, in many cases approaching the entire cost. Physicians and patients in these countries look to the United States and the European Union for guidance on effective treatment options.

Although the rise in health care costs is multifactorial, many of us, particularly oncologists and hematologists, repeatedly ask ourselves the following questions: “Why are cancer drugs so expensive?” “What polices or interventions can be employed to lower the cost of cancer drugs?” The comments and perspectives herein are intended to stir debate and discussion. Our goal is to provide an overview of the major operant factors from a physician's perspective.

Why Are Cancer Drugs So Expensive?

The high cost of cancer drugs is related to numerous factors. It is very expensive to move findings from bench to bedside and to perform all the regulatory studies (including phase 1, 2, and 3 clinical trials) to gain approval. Second, because most cancers are incurable, patients are treated with each approved agent (sequentially or in combination), creating a virtual monopoly because the use of one drug does not automatically mean that the others are no longer needed. Third, even when the monopoly is broken with the arrival of “new and improved” versions of an approved drug, the older (and by now generic) drug tends to be viewed as substandard treatment, thereby perpetuating the situation. Fourth, the very nature of cancer, and the seriousness of the diagnosis, plays a role in that patients and physicians are often willing to pay the high price of treatment even for marginal improvements in outcome. Finally, our systems provide an incentive to administer more chemotherapy, and there are legal barriers that prevent agencies such as the FDA from taking economic and cost-effectiveness considerations into account when approving new drugs.”

“Every drugs is registered for specifically indication, at the same time every drug to be a rational therapy need a rational decision making system that require a multidisciplinary team that can cover all aspect of pharmaceutical molecular metabolism kinetics and pharmacodynamics this create great possibility for clinical pharmacist but it must increase expertise in field of diagnostic (lab medicine and imaging) for the high relationship whit drug therapy.The old algorithm was “physicians - patients - classic pharmacist” m luisetto editorial an useful instrument in today healthcare j.ph. care and health omics 2016

“We submit to the scientific community “Clinical Pharmaceutical Care”as a new discipline .Discipline intended to improve clinical and economic endpoint in pharmacological therapy reducing therapy errors and with a more rational application of resource in medical team (clinical pharmacist).This new approach take advantages using the Management and ICT principles. We ask also to international organization involved in hospitals accreditation and University to recognize this new health care professional activity. We think that core training must include principles of Management, ICT Professional social media, psychological behavior skills for team working added to be added to the classic clinical pharmacy programs.

Theory and practical applications:

Also the knowledge in field of medical laboratory and imaging give a

great advantages in this new discipline for the hard relationship with

many drug therapy .For this reason also clinical pharmacist must be

involved. We strongly ask to public institution to apply this new

discipline to obtain more rational drug” m luisetto r. Sahu clinical pharmaceutical care a new management healthcare discipline ukjpb2016

Discussion

Under the light of this results finded (in this paper but also in other biomedical literature) in actual situation ( economical but also few disponiblity of new and really efficacy drugs or new delivery systems ) we can say that today is necessary to more really evaluate efficacy of drugs in registrative protocols.

This in order to have drugs with relevant profile of efficacy and a systems that allow to differenciate the molecule only for research study (with low activity profile that justify the use in therapy) from the real efficacy molecule to apply in therapy

The question is we need about new anticancerd drugs that little improves clinical otcomes or we need to have a new heavy process to register the new drugs?

We need other drugs copy or we need new pharmaceutical mechanism for anticancer treatment ?

Who must pay for copy drugs whit little improvement in clinical outcome s?

Is etical to pay for lower efficacy therapy ?

Conclusion

We don’t say that Is wrong use the actual drugs registerd for neoplasia treatment in the cycle and protocols approved ( in example gold standard) but we say only that In registering process is necessary for new drugs that the real relevant efficacy is verified to justify the current use in therapy and the cost involved.

The costs involved in today anticancer therapy are very high and the systems must be more under

Control in order to use economic resource only to have a relevant increase in clinical hard endpoint .

We think that the participation of clinical pharmacist in stabile way in oncological medical team can

Contribute to cost containment.

This costs involved we think need a management task to correct use the economic resource aviable today

Is also a ethical problem.

And the multidiplinarity is the right keywors ( stabile presence of clinical pharmacist in oncological medical team)

So we ask to pubblis institution to strictly apply this multidisciplinary way of working in order to

Achieve rational drug use policy .

References

1) Osman Slipicevic1 and Izet Masic2Mater Sociomed. 2012; 24(2): 106–111.Management Knowledge and Skills Required in the Health Care System of the Federation Bosnia and Herzegovina

2) Davis K1, Stremikis K. J Health Adm Educ. 2008 Winter;25(1):5-15.Measuring and improving health system performance: what can healthcare management educators do?

3) Garman AN1, McAlearney AS, Harrison MI, Song PH, McHugh M. Health Care Manage Rev. 2011 Jul-Sep;36(3):201-13. doi: 10.1097/HMR.0b013e318201d1bf.High-performance work systems in health care management, part 1: development of an evidence-informed model.

4)2015 Pharmacist Cognitive Service and Pharmaceutical Care: Today and Tomorrow Outlook, M. Luisetto, F. Carini, G. Bologna, B. Nili-Ahmadabadi, UKJPB UK Journal of Pharmaceutical and Biosciences Vol. 3(6), 67-72, 2015 [Source]

5)m luisetto editorial 2016 An Useful Instrument in Future Health Care Systems int journal of ph. Care and health systems omics Luisetto, J Pharma Care Health Sys 2016, 3:2

6)Recenti Prog Med. 2016 Apr;107(4):181-5. [Is the price of cancer drugs related to the cost of develo-pment and production or to the economic value of their clincal efficacy?].

Russi A1, Serena M2, Palozzo AC1.

7) J Immunother. 2015 Sep;38(7):259-66. Statistical Considerations in Clinical Trial Design of Immunotherapeutic Cancer Agents.Dranitsaris G1, Cohen RB, Acton G, Keltner L, Price M, Amir E, Podack ER, Schreiber TH.

.

8)Recenti Prog Med. 2016 Apr;107(4):181-5.

[Is the price of cancer drugs related to the cost of develo-pment and production or to the economic value of their clincal efficacy?].

Russi A1, Serena M2, Palozzo AC1.

9)Z Evid Fortbild Qual Gesundhwes. 2013;107(2):120-8. doi: 10.1016/j.zefq.2013.02.003. Epub 2013 Apr .[Cancer: Is it really so different? Particularities of oncologic drugs from the perspective of the pharmaceutical regulatory agency]. Enzmann H1, Broich K.

107)Cancer Res Treat. 2012 Mar;44(1):1-10. doi: 10.4143/crt.2012.44.1.1. Epub 2012 Mar 31.

Present status and problems on molecular targeted therapy of cancer.

Saijo N1.

11) Oncology (Williston Park). 2006 May;20(6 Suppl 5):10-8.

Historic evidence and future directions in clinical trial therapy of solid tumors.

Gollob JA1, Bonomi P.

12) Clinical Pharmaceutical Care, Medical Laboratory Imaging, Nuclear Medicine: A Synergy to Improve ClinicalOutcomes and Reducing Costs, M. Luisetto, J App Pharm 2016, 8:3 [Source]

13) Steps and Impacts of Pharmaceutical Care and Clinical Pharmacy Development on Clinical Outcomes 2016: A

Historical Analysis Compared with Results, M. Luisetto, B. Nili-Ahmadabadi, L. Cabianca, M. IbneMokbul,,

Clinicians Teamwork, 2016, 1:4-8 [Source]

14) An Open Letter to All Clinical Pharmacists: 2016, Pharmaceutical Care, Medical Laboratory, Nuclear Medicine

and Imaging, M. Luisetto, B. Nili-Ahmadabadi, Clinicians Teamwork, 2016, 1:1-3 [Source]

15) Bond CA, Raehl CL. Clinical pharmacy service , pharmacy staffing, and hospital mortality rates. Pharmacotherapy. 2007; 27(4): 481-93.

16) clinical practical guideline ASCO 2015 pancreas cancer

17)chronic myeloid leukaemia ASCO 2015 guideline

18) What Constitutes Reasonable Evidence of Efficacy and Effectiveness to Guide Oncology Treatment Decisions? The oncologist march 2010 vol 15 Daniel Sargent Author Affiliations Mayo Clinic, Rochester, Minnesota, USA

19) Ann Intern Med. 2009 Aug 4;151(3):206-9. Epub 2009 Jun 30.

Rethinking randomized clinical trials for comparative effectiveness research: the need for transformational change.Luce BR1, Kramer JM, Goodman SN, Connor JT, Tunis S, Whicher D, Schwartz JS.

20 ) jama oncology Five Years of Cancer Drug ApprovalsInnovation, Efficacy, and Costs Sham Mailankody, MB BS1; Vinay Prasad, MD, MPH1 July 2015, Vol 1, No. 4 >

21) Mayo Clin Proc. 2012 Oct; 87(10): 935–943.doi: 10.1016/j.mayocp.2012.07.007

PMCID: PMC3538397The High Cost of Cancer Drugs and What We Can Do About It

Mustaqeem Siddiquia and S. Vincent Rajkumarb,⁎Author information ► Copyright and License information ►

WEBSITES

15) FDA http://www.fda.gov/

16) EMA http://www.ema.europa.eu/ema/

17) AIFA http://www.agenziafarmaco.gov.it/