ANTINEOPLASTIC DRUGS: A FOCUS ON FEATURES OF …

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Litvinova et al. World Journal of Pharmacy and Pharmaceutical Sciences

ANTINEOPLASTIC DRUGS: A FOCUS ON FEATURES OF

REGISTRATION, IMPROVING THE QUALITY OF CLINICAL

TRIALS USING A PATIENT-CENTERED LOGISTICS APPROACH

Elena Litvinova*, Olga Posilkina, Svitlana Kovalenko and Anastasiia Lisna

Department of Management, Economy and Quality Assurance in Pharmacy, National

University of Pharmacy of the Ministry of Health of Ukraine, Kharkiv, Ukraine.

ABSTRACT

The aim of the work is to analyze and summarize existing scientific

approaches and mechanisms for fast-track approvals, improving the

quality of antineoplastic drugs clinical trials using a patient-centered

logistics approach. Materials and methods: Databases of the Internet,

such as PubMed, the Food and Drug Administration, the European

Medicines Agency, State Expert Center of the Ministry of Health of

Ukraine were used. The retrospective, logical, and graphical methods

of research, as well as the content analysis were applied. Results: One

of the main problems of antineoplastic drugs authorization is often

significant uncertainty about the degree of clinical benefit of new drugs

when entering the market. In order to improve the quality of clinical

research in the authorization of antineoplastic drugs, post-marketing

studies with clinically significant endpoints and a representative

composition of participants, pharmacovigilance, are of great importance. Within clinical

research, endpoints should be clinically relevant, sensitive to therapy, well measurable and

interpretable. A comprehensive evaluation of performance indicators allows an adequate

assessment of the ratio of the expected benefit to the possible risk of using antineoplastic

drugs. The introduction of a patient-centered logistics approach, including the use of modern

information technologies, social networks, crowdsourcing, patient self-education,

personalized medicine in clinical trials of antineoplastic drugs also contributes to improving

their quality during authorization. Conclusions: The analysis of the most acceptable

endpoints and the use of a patient-centered logistics approach is becoming increasingly

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 10, Issue 7, 22-37 Research Article ISSN 2278 – 4357

*Corresponding Author

Dr. Elena Litvinova

Department of Management,

Economy and Quality

Assurance in Pharmacy,

National University of

Pharmacy of the Ministry of

Health of Ukraine, Kharkiv,

Ukraine.

Article Received on

26 April 2021,

Revised on 16 May 2021,

Accepted on 06 June 2021

DOI: 10.20959/wjpps20217-19279


23


important in clinical trials of antineoplastic drugs, contributing to an increase in the efficiency

and quality of research.

KEYWORDS: quality assurance, patient-centered logistics approach, clinical trials,

antineoplastic drugs.

INTRODUCTION

Cancers occupy a significant place in the structure of morbidity and mortality of the

population, being the cause of 15% of all deaths in the world. Cancer ranks second in the

global mortality pattern, and first in a number of economically developed countries. In 2018,

9.6 million people in the world died of cancer. Overall, 70% of malignant deaths occur in

low- and middle-income countries, where mortality is 75%, compared with 46% in high-

income countries.[1]

Due to the aging population and the prevalence of risk factors (obesity, smoking, poor

nutrition, etc.), the incidence of oncopathology is increasing. In 2012, 14.1 million cases were

diagnosed in the world, in 2018 – 18.1 million, in 2030 21.4 million cases are predicted, and

by 2035 the incidence of cancer may double compared to 2012. The fastest increase in

incidence is predicted in low- and middle-income countries, which currently account for 60%

of first-time diagnosed cancers and only 5% of global economic spending.[2-4]

The results of

the University College and Health Data Research Centre study suggest that COVID-19 can

also increase mortality by 20% in first-time diagnosed oncopathology.[5]

According to the updated data of the National cancer registry of Ukraine in 2018, 137,968

new cases of oncopathology were identified, the crude rate was 384.7 per 100 000 of

population. The crude rate was 381.4 per 100 000 of population in 2017, 349.5 per 100 000

of population in 2016. Statistics show that the incidence increases from year to year. It should

also be noted that the world standardized rate is 225.0 per 100 000 of population, while in

Ukraine this rate is 350.9, respectively.[6]

Thus, the problem of oncology is one of the most relevant problems of the healthcare system

and Ukraine as a whole. Reasons for the high morbidity and mortality are the late diagnosis

and inaccessibility of modern antineoplastic drugs, a long period of clinical trials, the lack of

an individual approach to cancer patients.


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Cancer control is one of the priority areas of health care around the world. According to the

United Nations Sustainable Development Goals, cancer mortality is planned to be reduced by

one third by 2030. To achieve this goal, it is necessary to provide all patients with high-

quality medical care, including high-quality, effective, safe and economically affordable

medicines, which play a significant role in improving prognosis.[7]

Antineoplastic drugs are one of the largest groups of newly registered medicines. According

to a report by the European Medicines Agency (EMA), more than 25% of drugs approved in

2017 are antineoplastic drugs.[8]

According to a report by Center for Drug Evaluation and

Research (CDER, USA), in 2019, 48 innovative medicines were recommended for use, of

which 11 were antineoplastic drugs.[9]

This is primarily due to the high level of morbidity and

mortality in the world from cancers, the concentration of efforts of world organizations,

scientists, manufacturers in this direction, and scientific breakthroughs in the field of studying

the tumor process.

Despite this, the problem of deficiency of effective antineoplastic agents remains in the

world. This precedent created the conditions for introducing approaches to the global

regulatory practice, which are aimed at reducing the time for registration of medicines.[10]

The approaches of the regulatory authorities of the USA, the European Union, despite some

differences, share a common objective of accelerated approval of drugs that fill an unmet

medical need. One of the main problems of antineoplastic drugs authorization is often

significant uncertainty about the degree of clinical benefit of new drugs when entering the

market. The simplified authorization procedure is introduced in Ukraine for medicinal

products registered by competent authorities of the United States of America, Switzerland,

Japan, Australia, Canada and medicinal products registered via the centralized procedure by

the European Union competent authority. In the case of providing an opinion on registration,

the Ministry of Health within 7 working days decides on the state registration of medicines or

the refusal of the approved order of the Ministry of Health.

A huge number of scientific works are devoted to the problems of creating and

implementation of antineoplastic drugs into medical practice. Fundamental theoretical and

practical aspects of the quality of clinical research and their authorization are considered in

the works of many scientists, in particular, Peter B.Bach,[11]

Nathan Cherny,[12]

Melina

Arnold,[13]

Ushkalova E.A,[14]

etc.


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In addition, in some cases there is insufficient clinical effectiveness, high toxicity of

antineoplastic drugs. These circumstances, despite a wide range of extensive research, require

improving the quality of clinical research, taking into account the logistics approach to the

patient, using in some cases a simplified registration procedure in accordance with the

adopted legislation and implementation new antineoplastic drugs.[15,16]

One of the main problems of antineoplastic drugs authorization is often significant

uncertainty about the degree of clinical benefit of new medicine when entering the market. In

oncology, new medicines and new indications are often approved in earlier stages of

development based on surrogate endpoint data or data from non-randomized studies, which

may lead to a reassessment of clinical benefit. Although this is largely due to the desire to

facilitate rapid access to promising treatments in the area of unmet medical need.

The aim of the work is to analyze and summarize existing scientific approaches and

mechanisms for fast-track approvals, improving the quality of antineoplastic drugs clinical

trials using a patient-centered logistics approach.

MATERIALS AND METHODS

Studies were conducted using databases on the Internet: PubMed; Food and Drug

Administration, the European Medicines Agency, State Expert Center of the Ministry of

Health of Ukraine. The retrospective, logical, and graphical methods of research, as well as

the content analysis were applied.

RESULTS AND DISCUSSION

The high level of antineoplastic drugs authorization is associated with scientific

breakthroughs in the field of oncology research and the expectations of patients for whose

diseases today there is no effective therapy. The FDA, EMA and other regulators allow for

some medicines to have fast-track approvals to get to patients earlier. Antineoplastic drugs

are registered under a simplified protocol more often than medicines of other groups.

Table 1 shows the elapsed time between date of first marketing authorization (out of the

sample countries) and marketing authorization in subsequent countries/regions for each

product/indication pair in the sample approved since 2014 (n = 31). Among 31 new

product/indication pairs in the sample approved since 2014, 26 obtained their first marketing

authorization in the United States, while 4 were first approved in Japan and 1 in Switzerland.


26


All European countries except Switzerland have been grouped into the European Economic

Area (EEA) as marketing authorization is centralized for oncology products. On average,

products and indications were approved in individual countries/regions 12 to 17 months after

their first marketing authorization in the sample of countries surveyed (range 2 to 52 months

for individual pairs).[17]

Table 1: Time between first marketing authorization and marketing authorization in

subsequent countries/regions for product/indications approved since 2014 (n=31 pairs).

Indication Active

pharmaceutical

ingredient

First marketing

approval

Time since first marketing approval and

subsequent approval in each country/region in

months (number of pairs approved, with

information on dates1)

Country Date USA

(31)

EEA

(29)

JPN

(25) ISR

2

(20)

CHE

(25)

KOR

(21)

CHL (9)

Metastatic

breast cancer

Abemaciclib USA Sep-17 0 12 12 15 20 20 27

Olaparib USA Dec-14 0 52 43 b 13 8 a

Palbociclib USA Feb-15 0 21 31 b 23 18 b

Ribociclib USA Mar-17 0 5 a b 7 a b

Talazoparib USA Oct-18 0 8 a a a a a

Non-small

cell lung

cancer

Alectinib JPN Sep-15 3 17 0 7 16 13 c

Atezolizumab USA May-16 0 16 20 13 12 8 9

Brigatinib USA Apr-17 0 19 a 19 a 19 a

Ceritinib USA Apr-14 0 13 23 13 16 9 8

Dacomitinib USA Sep-18 0 7 4 a 11 a a

Durvalumab USA May-17 0 16 14 9 13 19 a

Lorlatinib JPN Sep-18 2 8 0 a a a a

Necitumumab USA Nov-15 0 3 43 17 a a a

Nivolumab USA Dec-14 0 10 12 3 11 3 12

Osimertinib USA Nov-15 0 3 4 6 8 6 31

Pembrolizumab USA Oct-15 0 9 14 c 16 c c

Ramucirumab USA Apr-14 0 21 26 25 9 12 12

Colorectal

cancer

Nivolumab USA Dec-14 0 a a 3 11 3 12

Pembrolizumab USA Sep-14 0 a 51 5 29 6 a

Ramucirumab USA Apr-14 0 21 25 25 18 12 12

Trifluridine /

Tipiracil

JPN Mar-14 18 25 0 a 41 a a

Melanoma Binimetinib USA Jun-18 0 3 7 a a a a

Cobimetinib CHE Aug-15 3 3 a 10 0 3 8

Encorafenib USA Jun-18 0 3 7 b a a a

Nivolumab JPN Jul-14 5 11 0 8 16 8 b

Pembrolizumab USA Sep-14 0 10 24 5 29 6 b

Talimogene

Laherparepvec

USA Oct-15 0 2 A 28 9 a a

Multiple

myeloma

Daratumumab USA Nov-15 0 6 22 14 13 24 b

Elotuzumab USA Nov-15 0 6 10 10 13 12 b


27


Ixazomib USA Nov-15 0 12 16 9 15 20 a

Panobinostat USA Feb-15 0 6 5 a 10 24 b

Average length of time per country/region for

pairs studied

1 12 17 15 15 12 15

Median length of time per country/region for

pairs studied

0 10 14 13 13 12 12

Note: a = product/indication pair not approved (or not launched); b = product/indication pair

approved but marketing authorization date not provided; c = no data provided for that

product/indication pair

All European countries except Switzerland have been grouped as marketing authorization in

the European Economic Area (EEA) is centralized for oncology products. Australia did not

provide data on dates.

1. Israel and Chile provided information on dates only for a subset of product/indication

pairs indicated as “approved and covered”

2. For products with several indications, data represent product-level dates only. Indication-

specific dates are not available. Source: Authors based on 2019 OECD survey on

challenges in access to oncology medicines.

Globally, between 2013 and 2017, 45 new oncology drugs entered the market, many of them

approved for multiple indications or for use within a combined therapy regimen. The number

of approved indications increased by 265 to 935 during this period, an average of five

indications per new active substance. In 2018, 75% of targeted therapies were used in

multiple indications.[17]

The use of medicines outside the indications approved by the regulator (“off-label use”) is

very common in cancer. Because oncology remains a therapeutic area of high unmet need,

prescribers and patients are often willing to accept the use of medicines in circumstances in

which their efficacy and safety profiles have not yet been clearly established.[18,19]

Thus, significant progress has been made in recent years in the prevention and treatment of

certain forms of cancer, for example, cancer of the esophagus, stomach, pancreas, lung,

ovarian and colorectal cancer, but the implementation of new methods of prevention and

therapy, especially in low- and middle-income countries, which include Ukraine, limited by

their high cost, including the high price of antineoplastic drugs.


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We have established that antineoplastic drugs authorization in Ukraine is most often carried

out according to the following types: full application; generic, hybrid or similar biological

application, accelerated approval of drugs. According to the Report of the State Expert Center

of the Ministry of Health of Ukraine, a nosological group – oncology (it has been registered

56 drugs) is leading among registered medicines in Ukraine in 2020. It was established that

among them there are no original domestic medicines. The percentage of registered generic

domestic antineoplastic drugs of their total number in the pharmaceutical market of Ukraine

is 4%. The analysis also revealed that the largest number of foreign antineoplastic drugs was

registered by groups: alkylating compounds, antimetabolites.

Table 2 shows the data of analysis and systematization of clinical data on the effectiveness of

antineoplastic drugs, which are registered according to the accelerated procedure abroad.

Table 2: Analysis and systematization of clinical data on the effectiveness of

antineoplastic drugs, which are registered according to the accelerated procedure

abroad.

Type of study Result

Meta-analysis, 2019 Analysis of surrogate validation studies (n=78), it has been found most

surrogates in oncology had low or modest correlation with overall

survival, which suggests that caution should be used when making

conclusions based on surrogate markers[20]

Review of FDA

(1992-2017)

The FDA published a review of 93 cancer drug indications for which

accelerated approval was granted from 1992, through 2017.

Confirmatory trials for 19 of 93 (20%) cancer drug approvals reported an

improvement in overall survival, 19 (20%) reported improvement in the

same surrogate used in the preapproval trial, and 20 (21%) reported

improvement in a different surrogate. Confirmatory trials for one-fifth

(n = 19 of 93) of cancer drug indications approved via the FDA’s

accelerated approval pathway demonstrated improvements in overall

patient survival[21]

Review of

antineoplastic drugs

that are approved,

FDA 2009-2017, and

EMA through 2018

The study cohort included 63 drugs approved by the FDA and the EMA

during the study period. 46 (73%) were approved for solid tumors, and

17 (27%) were approved for hematologic malignancies. Overall, median

cancer drug prices in included European countries were 52% lower than

US prices. There was no statistically significant association between

monthly treatment cost and ASCO-VF or ESMO-MCBS scores in any

country. There was also no association between price differential

between US and median European drug prices and either ASCO-VF or

ESMO-MBCS scores. Thus, cancer drug prices in the US were

significantly higher than in the compared European countries. Drug

prices of cancer drugs were not associated with clinical benefit in the US

or in European countries[22]


29


This data suggest that most surrogates in oncology had low or modest correlation with overall

survival, which suggests that caution should be used when making conclusions based on

surrogate markers.

In addition, ensuring the economic accessibility of antineoplastic drugs is currently one of the

main tasks of international organizations in the field of oncology. Potential ways to address

the challenges associated with high prices of new cancer medicines, and at times limited

health gain versus current standards, could include agreeing among European authorities

what is meant by a “meaningful clinical benefit” for a new cancer medicine. Ferguson and

colleagues in the United Kingdom suggested that no premium should be paid for a new

cancer medicine unless it prolonged survival by at least three months compared with existing

standards. There were similar timescales for deliberations regarding the value of new

medicines at the end of life in the United Kingdom. The American Society of Clinical

Oncology Cancer Research Committee recently identified an improvement in median overall

survival in a range of 2.5-6 months across a range of tumors as the minimum incremental

improvement that would define a clinically meaningful outcome for a new cancer medicine

(extent would depend on the tumor type).[23,24]

By order No. 593 of the Ministry of Health of Ukraine of March 29, 2021, the guideline for

state assessment of medical technologies for medicines was approved. According to the

guideline, the methodological quality of each study included in the target-analysis or

systematic examination should be assessed, since this affects the reliability and validity of the

test data. Assessment of the quality of any study should take into account: compliance of the

study design with the research goal; risk of bias (due to improperly planned study design or

data collection, analysis, interpretation, publication or inspection); other issues related to the

quality of the study; selection of the result measurement tool statistical analysis issues;

quality of primary source reporting; quality of intervention; general conclusion. Based on

expert opinions and recommendations, medical technology is selected for the appropriate

treatment regimen, which will be the most clinically effective, safe and cost-effective and

will cover the most patients to address unmet needs.

Among the main measures aimed at ensuring the economic accessibility of antineoplastic

drugs is the wider implementation of generics and biosimilars into medical practice,[25]

and

their fast-track approvals in accordance with the law.


30


Analysis and systematization of data on current requirements for antineoplastic drugs

authorization in Ukraine found that post-marketing studies with clinically significant

endpoints and representative composition of participants, pharmacovigilance, are of great

importance.

Analysis of problems related to selection of the most acceptable endpoints of clinical

effectiveness of antineoplastic drugs has been carried out. It is shown that currently the

criteria for assessing the clinical effectiveness of antineoplastic drugs are “patient- centered”

(overall survival and quality of life) and “tumor- centered” (response to therapy, progression-

free survival, disease-free survival) endpoints.[26]

The overall survival score as the primary endpoint is the “gold standard” demonstrating the

clinical efficacy of antitumor therapy for patients. The FDA recognized this indicator as a

universal criterion for assessing clinical efficacy and the best endpoint for phase III clinical

trials. Predicting the exact life expectancy for an individual patient is an extremely difficult

task. To assess survival, doctors use statistics obtained from clinical studies in which a large

number of patients with certain types and stages of tumors participated.

In clinical studies of antineoplastic drugs, particular importance is given to the indicator of

quality of life of patients assessing the subjective response to treatment with the help of

special questionnaires, which are completed during treatment.

Currently, in oncology practice, the use of a “tumor-oriented” clinical endpoint has acquired

relevance – progression-free survival, which has an earlier time frame for evaluating efficacy

and reduced impact of further therapy regimens. As a rule, this term refers to the period of

time from the moment of randomization to the moment of tumor recurrence or death for any

reason after receiving antitumor therapy.

In studies, the indicator of disease progression is defined differently: as clinical or

radiological progression (criteria for assessing the response of solid tumors RECIST,

Response Evaluation Criteria In Solid Tumors, take into account linear sizes of neoplasms) or

as laboratory measurements of progression, which makes it difficult to compare the results.

Subjective response rate is assessed by change in status, reduction or disappearance of

disease symptoms (particularly pain), and change in body weight. Perfomance status is

assessed before the start of treatment, during treatment and after its completion according to


31


the WHO 5-stage system (ECOG-WHO, Eastern Cooperative Oncology Group - World

Health Organization).

The characteristics of the recommended endpoints of clinical effectiveness of antineoplastic

drugs,[26]

including the advantages and disadvantages of using a particular indicator, as well

as the requirements for its evaluation, are systematized and presented in Figure 1.

Criteria for assessing the clinical effectiveness of antineoplastic drugs

Should be: clinically relevant, sensitive to therapy, well-measurable and interpreted

“Patient- Centered” endpoints

Direct Clinical Efficacy

“Tumor-centered” endpoints

Indirect clinical efficacy

Overall survival

(beginning of study - death)

Time from the start of the

study (randomization,

patient inclusion, drug

initiation, etc.) to death from

any cause.

Need a large patient

population and long-term

follow-up

Quality of life

Reduce study duration and be

able to assess clinical benefit

The criterion is subjective,

characterized by insufficiency

of data and lack of

standardized approaches for

analysis and presentation of

results

Evaluation of treatment

response with validated

questionnaires:

to determine quality of life -

QLQ-C30 EORTC

for functional evaluation of

antitumor therapy - FACT

Rotterdam Symptom Checklist

- RSCL

Functional Living Index-

Cancer - FLIC

Progression-free

survival

Earlier timing of

effectiveness

assessment while

reducing exposure

to detailed therapy

regimens

Time from the

start of the study

(randomization,

patient inclusion,

drug initiation,

etc.) to the

progression of

disease or death

from any cause.

Objective

response

Ability to change

or stop therapy in

a timely manner if

it is ineffective

The time from the

start of the study

(randomization,

patient inclusion,

drug initiation,

etc.) to the

objective

progression of

tumor growth

does not include

death.

Subjective

response

EGOS Status

Change

Disappearance of

disease symptoms

Body Weight

Change

Figure 1: Recommended endpoints of clinical efficacy of antineoplastic drugs.[26]

Therefore, “patient-centered” endpoints allow an assessment of the direct clinical benefit of

chemotherapy in patients, while “tumor- centered” endpoints that do not directly reflect the

clinical benefit to patients allow an assessment of efficacy at earlier stages. The analysis of

the most acceptable endpoints in order to interchange the primary criterion of effectiveness

(overall survival) is becoming increasingly relevant in oncology. The selection of clinical

efficacy criteria should take into account the characteristics of cancer, the study population

and the duration of therapy.

In recent decades, the use of a patient-centered logistics approach as a means of improving

the effectiveness of early and late phases of clinical research has gradually become


32


increasingly popular, in particular by increasing the likelihood of success of the study and

obtaining patients with more effective and safe therapy.[27,28]

Thus, the patient-centered logistics approach focuses on the patient as the most important link

in clinical research. The service for delivering everything necessary to the patient is the main

and extremely necessary service in the field of clinical research. Deliveries can be performed

in various variations, depending on the requirements of the Sponsor, the storage temperature

of the drug, urgency, etc. Delivery of medicines directly to the patient helps to reduce the

number of visits, and also helps to reduce the research budget as a whole. To date,

temperature-controlled deliveries directly to the patient are simply necessary for clinical

research. The possibility of direct deliveries to the patient becomes a requirement of sponsors

when starting mainly studies. At the same time, a logistics chain must be built with

temperature control, storage of the drug, urgency, etc.

The pandemic COVID-19 highlighted the need to optimize logistical processes. After all, the

patient can participate in a clinical trial without leaving home. There is no need for travel or

forced visits to medical facilities – even for the preparation of initial documentation. This

flexible approach enables the patient to act. According to experts, there will be a “hybrid”

approach that will combine remote communication with patients along with their trips to the

nearest medical institutions.[29]

Ways to improve clinical research, based on a patient-centered logistics approach, also

include using open channels of communication between the company, doctors, patients and

the media, increasing the focus on education, attracting and maintaining patients through

technology. So, the FDA launched Project Patient Voice, an initiative of the FDA’s Oncology

Center of Excellence (OCE). The pilot phase of the project currently underway is limited to

one clinical trial (an open randomized phase III trial that would compare TAGRISSO

(osimertinib) with platinum-based doublet chemotherapy in patients with lung cancer). The

goal is to get feedback from the public about the practical aspects of using the resource.

Patient Voice is an online platform for patients, caregivers, and healthcare providers to

familiarize them with symptoms reported by clinical trial participants. These data are

generally not available in U.S. medicine prescribing information (instructions), but may

provide additional information for healthcare professionals to discuss with patients and

caregivers.[30]


33


Oncological diseases of the same type are characterized by significant differences in the

genetic composition and features of each patient. In the clinic, this variation results in patients

responding differently to therapy. To address this issue, the realm of personalized medicine

aims to combine genetic perceptions of cancers with other clinical and diagnostic information

to identify patterns that may allow clinicians to predict patients’ response to therapy and

select the most effective interventions.

Researchers from Queen Mary University of London have developed a machine learning

algorithm that ranks drugs based on their efficacy in reducing cancer cell growth. The

approach may have the potential to advance personalized therapies in the future by allowing

oncologists to select the best drugs to treat individual cancer patients. The method, named

Drug Ranking Using Machine Learning (DRUML), is based on machine learning analysis of

data derived from the study of proteins expressed in cancer cells. Having been trained on the

responses of these cells to over 400 drugs, DRUML predicts the best drug to treat a given

cancer model.[31]

Thus, the implementation of a patient-centered logistics approach is widely used in oncology.

The pharmaceutical industry, faced with significant organizational and financial challenges,

is looking for ways to improve the effectiveness and quality of clinical research.

CONCLUSIONS

1. Analysis of domestic and foreign literature shows that oncological diseases occupy a

significant place in the structure of morbidity and mortality of the population, being the

cause of 15% of all deaths in the world. In Ukraine, the problem of oncology is also one

of the most pressing problems of the healthcare system.

2. The approaches of the regulatory authorities of the USA, the European Union, despite

some differences, share a common objective of accelerated approval of drugs that fill an

unmet medical need. One of the main problems of antineoplastic drugs authorization is

often significant uncertainty about the degree of clinical benefit of new drugs when

entering the market. Antineoplastic drugs are registered under a simplified protocol more

often than medicines of other groups.

3. In order to improve the quality of clinical research in the authorization of antineoplastic

drugs, post-marketing studies with clinically significant endpoints and a representative

composition of participants, pharmacovigilance, are of great importance. Within clinical

research, endpoints should be clinically relevant, sensitive to therapy, well measurable


34


and interpretable. A comprehensive evaluation of performance indicators allows an

adequate assessment of the ratio of the expected benefit to the possible risk of using

antineoplastic drugs.

4. The introduction of a patient-centered logistics approach, including the use of modern

information technologies, social networks, crowdsourcing, patient self-education,

personalized medicine in clinical trials of antineoplastic drugs also contributes to

improving their quality during authorization. The implementation of patient-centered

logistic strategies of clinical trials increases the level of patient satisfaction, loyalty and

preferences.

CONFLICTS OF INTEREST

The authors declare that they have no conflicts of interest.

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