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Disinvestment. Ana Luísa Caires de Souza
1. Authors:
Ana Luísa Caires de Souza
Francisco de Assis Acurcio
Augusto Afonso Guerra Júnior
Renata Cristina Rezende Macedo do Nascimento
Leonardo Maurício Diniz
2. Insulin analogues: safety, efficacy and comfort
Glargine
• 2000 EMEA
• 2003 ANVISA
Expectation
Hypoglycaemic episodes Marketing Judicialization Medicines List
Comfort strategy SES/MG/2005
Administrative requests: 2,632
Expenses of Minas Gerais State Treasury with glargine grew an average of 291% per
year, reaching almost USD 6 million/2011.
3. Glargine expenses in Minas Gerais State, Brazil (2007-2011)
Costs: Glargine > 536% NPH
2009: Glargine and cancer
Systematic Review: Efficacy and safety of glargine in T1DM.
4. OBJECTIVE
To assess the efficacy and the safety of glargine in order to evaluate the
pertinence of maintenance the drug on the list of SUS from Minas Gerais
State in Brazil.
5. Search
MEDLINE;
Latin American and Caribbean Centre on Health Sciences Information;
Cochrane Controlled Trials Databases ;
National Health Service (NHS) Centre for Reviews and Dissemination.
Software
Reference Manager
Keywords
Portuguese, English, Spanish.
Health Condition Intervention Study Type
T1DM Glargine insulin, NPH insulin, Regular Efficacy
Glycated hemoglobin insulin, Animal NPH Effectiveness
Hypoglycemia insulin, Recombinant NPH Cost effectiveness
Diabetes complications insulin, Animal regular
insulin, Recombinant regular insulin
6. Inclusion Criteria
Intervention: glargine monotherapy or combination regimens with other insulins.
Exclusion Criterias
languages other than English, Portuguese or Spanish;
not performed in human;
unrelated to T1DM;
Not present at least one of the outcome measures of efficacy or safety.
Systematic Reviews of Clinical Trials identified in the search process were used for
comparison and discussion of results.
7. Titles and abstracts analysis
2 reviewers;
Discordant: 3rd reviewer.
Outcomes measure
blood concentration of glycated hemoglobin;
measures of glucose;
episodes of hypoglycemia;
reduction of microvascular and macrovascular events;
adverse effects.
Assessment of risk of bias
Modified Jadad Scale (JADAD, 1996)
8. Schematic presentation of the articles included and excluded in the systematic review
Studies initially identified in the search:
803
Excluded abstracts: 79 Excluded titles: 666
Reasons Reasons
Not performed in humans: 6 Not performed in humans: 9
Not related to T1DM: 4 Not related to T1DM: 108
Included titles: 137
Not presenting comparative Not presenting comparative
results regarding the efficacy/ results regarding the efficacy/
effectiveness of the studied drug: effectiveness of the studied drug:
64 546
Not presenting at least one of the Not presenting at least one of the
outcome measures of outcome measures of
efficacy and/or efficacy and/or safety consideration:
safety consideration: 5 3
Studies included in the final review: 58
Observational studies: 50
Clinical trials: 8
9. Modified Jadad Scale
Intention to Treat
Randomisation
Randomisation
Randomisation
Inappropriate
Appropriate
Appropriate
Withdrawal
Dropout/
Analysis
Blinding
Blinding
Score
Article
Rosenstock et al., 200017 1 0 0 0 0 1 1 3
Raskin et al., 200015 1 1 0 0 0 1 1 4
Pieber et al., 200013 1 0 0 0 0 0 0 1
Schober et al., 200218 1 0 0 0 0 1 1 3
Doyle et al., 20045 1 1 0 0 0 1 1 4
Chatterjee et al., 20072 1 1 0 0 0 1 0 3
Chase et al., 20081 1 0 0 0 0 1 1 3
White et al., 200922 1 0 0 0 0 1 0 2
Mean score: 2,87
None estudy with scored 5-6
No double-blind study
Conflict of interest: 7 trials
10. Characteristics of the selected clinical trials
7 Glargine x NPH, 1 Glargine x Aspart , 0 Glargine x Detemir;
Median participants: 168 (<32 e >619);
Median follow-up: 4 months (1 month, 2 years);
Basal therapy: glargine 1x/day x NPH 1x or 2x/day;
Prandial component: lispro, aspart or regular.
11. Characteristics of participants and interventions in selected clinical trials
1591 participants
Gender
• female: 56,7%
Age
• Minimum age: 5 years
• Maximum age: 80 years
Associated comorbidities were investigated but were not discussed in the selected
studies.
BMI: there were no changes (Chase et al., 2008; Doyle et al., 2004; and Chatterjee et al., 2007)
12. Advantages in the reduction of hypoglycemia and Glycated Hemoglobin (HbA1c)
Statistically significant
Statistically significant
advantage in the
Article advantage in the reduction
reduction of episodes of
of HbA1c
hypoglycaemia
Rosenstock et al., 200017 NPH *
Raskin et al., 200015 NS NS
Pieber et al., 200013 Glargine Glargine
Schober et al., 200218 ** NS
Doyle et al., 20045 ** Aspart
Chatterjee et al., 20072 NS Glargine
Chase et al., 20081 Glargine NS
White et al., 200922 * NS
* Not assessed in the study.
NS: No statistically significant advantage found.
**It was not presented p-value.
13. The trials did not show relevant differences in the adverse effects.
Chronic complications of diabetes, mitogenic effects attributed to glargine and other
possible long-term undesirable effects;
Cost-benefit ratio of glargine does not support its use, particularly in poor
countries, although it might be indicated in specific conditions when there are
sufficient resources (Gill et al, 2010). In Brazil, the cost of treating with glargine is
remarkably higher than that with NPH insulin;
The cost-effectiveness ratio seems to favour the use of the NPH. Manufacturer of
glargine should present the Unified Health System (SUS) managers reasons justifying
the higher cost of this drug, including novel evidence and more precise
measurements of its cost-effectiveness and impact on quality-adjusted life years
(QALYs).
14. The present systematic review did not find advantages of the treatment with
glargine compared to other investigated insulin formulations when glycemic
control and the frequency and the severity of episodes of hypoglycemia were
analyzed together. Furthermore, the available evidence is weak and is not enough.
For these reasons, the SUS State Manager was advised to disinvest or to
renegotiate the price of glargine with its manufacturer.
15. REFERENCES
1. Chase HP, Arslanian S, Neil HW, Tamborlane WV. Insulin Glargine Versus Intermediate-Acting Insulin as the Basal
Component of Multiple Daily Injection Regimens for Adolescents with Type 1 Diabetes mellitus. J Pediatr. Abr.
2008; 153:547-553.
2. Chatterjee S, Jarvis-Kay J, Rengarajan T, Lawrence IG, McNally PG, Davies MJ. Glargine versus NPH insulin: efficacy in
comparison with insulin aspart in a basal bolus regimen in type 1 diabetes--the glargine and aspart study (GLASS).
Diabetes Res Clin Pract. Ago. 2007; 77(2):215-222.
3. Cohen D, Carter P. How small changes led to big profits for insulin manufacturers. BMJ. 2010; 341:c7139.
4. Currie CJ, Poole CD, Gale EAM. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes.
Diabetologia. 2009; 52:1766-1777.
5. Doyle EA, Weinzimer SA, Steffen AT, Ahern JA, Vincent M, Tamborlane WV. A randomized, prospective trial
comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin
glargine. Diabetes Care. Jul. 2004; 27(7):1554-1558.
6. Gill GV, Yudkin JS, Keen H, Beran D. The insulin dilemma in resource-limited countries. A way forward? Diabetologia.
2010.
7. Hemkens LG, Grouven U, Bender R, Günster C, Gutschmidt S, Selke G W, et al. Risk of malignancies in patients with
diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia. Set. 2009; 52(9): 1732–
1744.
8. Institut für qualität und Wirtschaftlichkeit im Gesundheitswesen [Institute of Quality and Efficiency in Health Care].
Long-acting insulin analogues in the treatment of diabetes mellitus type 1 (2010).
Http://www.iqwig.de/download/A05-01_Executive-Summary_Long-
acting_insulin_analogues_in_diabetes_mellitus_type_1.pdf (Accessed Sep 2010).
16. REFERENCES
9. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of
randomized clinical trials: is blinding necessary? Control Clin Trials. 1996 Feb;17(1):1-12.
10. Jonasson JM, Ljung R, Talbäck M, Haglund B, Gudbjörnsdòttir S, Steineck G. Insulin glargine use and short-term
incidence of malignancies—a population-based follow-up study in Sweden. Diabetologia. Set. 2009; 52(9):1745-
54. Epub 2009 Jul 9.
11. Machado MAA, Acurcio FA, Brandão CMR, Faleiros DR, Guerra Júnior AA, Cherchiglia ML, Andrade EIG.
Judicialização do acesso a medicamentos no Estado de Minas Gerais, Brasil [Judicialisation of access to
medicines in the State of Minas Gerais, Brazil]. Rev Saúde Pública. 2011 Jun;45(3):590-8. Epub 2011 Apr 1.
12. Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues vs. NPH human insulin in type 1 diabetes: a
meta-analysis. Diabetes Obes Metab. Abr. 2009; 11(4):372-8.
13. Pieber TR, Eugene-Jolchine I, Derobert E. Efficacy and safety of HOE 901 versus NPH insulin in patients with type 1
diabetes. The European Study Group of HOE 901 in type 1 diabetes. Diabetes Care. Fev. 2000; 23(2):157-162.
14. Plank J, Siebenhofer A, Berghold A, Jeitler K, Horvath K, Mrak P, et al. Systematic Review and Meta-analysis of
Short-Acting Insulin Analogues in Patients With Diabetes mellitus. Arch Intern Med. Jun. 2005; 165(12):1325-
1444.
15. Raskin P, Klaff L, Bergenstal R, Halle JP, Donley D, Mecca T. A 16-week comparison of the novel insulin analog
insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes.
Diabetes Care. Nov. 2000; 23(11):1666-1671.
16. Rede Brasileira de Avaliação de Tecnologia em Saúde [Brazilian Network for Health Technology Assessment].
Boletim Brasileiro de Avaliação de Tecnologias em Saúde [Brazilian Bulletin of Health Technology Assessment].
Insulina Glargina e Insulina Detemir no Controle da Diabetes Mellitus Tipo 1 (2010) [Glargine insulin and detemir
insulin: the control of type 1 diabetes mellitus (2010)] http://bvsms.saude.gov.br/bvs/ct/pdf/brats2010_n13.pdf
(Accessed Feb 2011).
17. REFERENCES
16. Rede Brasileira de Avaliação de Tecnologia em Saúde [Brazilian Network for Health Technology Assessment].
Boletim Brasileiro de Avaliação de Tecnologias em Saúde [Brazilian Bulletin of Health Technology Assessment].
Insulina Glargina e Insulina Detemir no Controle da Diabetes Mellitus Tipo 1 (2010) [Glargine insulin and
detemir insulin: the control of type 1 diabetes mellitus (2010)]
http://bvsms.saude.gov.br/bvs/ct/pdf/brats2010_n13.pdf (Accessed Feb 2011).
17. Rosenstock J, Park G, Zimmerman J. Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1
diabetes on multiple daily insulin regimens. U.S. Insulin Glargine (HOE 901) Type 1. Diabetes Care. Ago. 2000;
23(8):1137-1142.
18. Schober E, Schoenle E, Van DJ, Wernicke-Panten K. Comparative trial between insulin glargine and NPH insulin in
children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. Abr. 2002; 15(4):369-376.
19. Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H. Efficacy and safety of insulin analogues for the management of
diabetes mellitus: a meta-analysis. CMAJ. Fev. 2009; 180 (4).
20. Smith U, Gale EAM. Does diabetes therapy influence the risk of cancer? Diabetologia. 2009; 52:1699–1708.
21. Vardi M, Eyal J, Asaph N, Haim B. Intermediate acting versus long acting insulin for type 1 diabetes mellitus.
Cochrane Database of Systematic Reviews. 2008.
22. White NH, Chase HP, Arslanian S, Tamborlane WV. Comparison of glycaemic variability associated with insulin
glargine and intermediate-acting insulin when used as the basal component of multiple daily. Diabetes Care.
Mar. 2009; 32 (3):387-393.
23. World Health Organization. 18th Expert Committee on the selection and use of Essential Medicines. Review of
the Evidence Comparing Insulin (Human or Animal) with Analogue Insulins (2011).
http://www.who.int/selection_medicines/committees/expert/18/applications/Insulin_review.pdf (Accessed
Feb 2011).
24. Zib I, Raskin P. Novel insulin analogues and its mitogenic potential. Diabetes, Obesity and Metabolism. 2006;
8:611–620.
18. THANK YOU!
Ana Luísa Caires
analuisacaires@gmail.com
Hinweis der Redaktion
Rounded corner rectangle tabs with inset pictures(Advanced)To reproduce the top rectangle (olive-green, “label one”) with text effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Rectangles, click Rounded Diagonal Corner Rectangle (ninth option from the left). On the slide, drag to draw a rectangle.On the Home tab, in the bottom right corner of the Drawing group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane, select Gradient fill in the right pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Down (first row, second option from the left).Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 32%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colors click Olive Green, Accent 3, Lighter 60% (third row, seventh option from the left).Also in the Format Shape dialog box, click Line Color in the left pane, select Gradient line in the right pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Up (second row, second option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colors click White, Background 1, Darker 25% (fourth row, first option from the left).Also in the Format Shape dialog box, click Line Style in the left pane. In the Line Style pane, in the Width box, enter 1 pt. On the Home tab, in the Drawing group, click Shape Effects, point to Glow, and then do the following:Under Glow Variations, select any option in the first row (5 pt glow options). Point to More Glow Colors, and then under Theme Colors click White, Background 1, Darker 25% (fourth row, first option from the left). On the slide, right-click the rectangle and then click Edit Text. Enter text in the text box and select the text. On the Home tab, in the Font group, select Gill Sans MT from the Font list and then select 24 from the Font Size list.On the Home tab, in the Paragraph group, click Align Text Left to align the text left within the rectangle.Under Drawing Tools, on the Format tab, in the WordArt Styles group, click the arrow next to Text Fill, click More Fill Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 127, Green: 127, and Blue: 127.Select the rectangle. On the Home tab, in the bottom-right corner of the Drawing group, click the Format Shapes dialog box launcher. In the Format Shapes dialog box, click Text Box in the left pane. In the right pane, under Internal margin, enter 1” in the Left box to increase the left margin in the rectangle to accommodate the embossed picture. Under Drawing Tools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.92”.In the Shape Width box, enter 4.5”.To reproduce the olive-green embossed picture for the top rectangle on this slide, do the following:On the Home tab, in the Drawing group, click Shapes, and then under Rectangles, click Rounded Diagonal Corner Rectangle (ninth option from the left). On the slide, drag to draw a rectangle.On the Home tab, in the bottom right corner of the Drawing group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane, select Picture or texture fill, and then under Insert from click File. In the Insert Picture dialog box, select a picture and then click Insert. Also in the Format Shape dialog box, click Line Color in the left pane. In the Line Color pane, select No line. Also in the Format Shape dialog box, click Picture in the left pane, click the button next to Recolor, and then under Light Variations click Accent color 3 Light (fourth option from the left).Also in the Format Shape dialog box, click Shadow in the left pane, and then do the following in the right pane:Click the button next to Preset, and then under Inner click Inside Diagonal Top Left (first row, first option from the left).In the Transparency box, enter 65%. Under Picture Tools, on the Format tab, in the bottom right corner of the Size group, click the Size and Position dialog box launcher. In the Size and Position dialog box, on the Size tab, do the following:Under Scale, select the Lock aspect ratio check box.Under Size and rotate, in the Height box, enter 0.75”. (Under Size and rotate, in the Width box, 0.75” will appear automatically.)Drag the picture onto the left side of the rectangle. Press and hold CTRL and select the picture and the rectangle. On the Home tab, in the Drawing group, click Arrange, point to Align, and then click Align Middle. To reproduce the other shapes on this slide, do the following:Press and hold CTRL and select the picture and the rectangle. On the Home tab, in the Drawing group, click Arrange, and then click Group. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Repeat the process until there is a total of four groups of shapes.Drag the groups so that they are distributed vertically on the slide. Press and hold CTRL and select all four groups. On the Home tab, in the Drawing group, click Arrange, and then do the following:Point to Align, and then click Align Center. Point to Align, and then click Distribute Vertically. Click Ungroup. To change the color and text for the duplicate rectangles (second, third, and fourth from the top), do the following:Select the rectangle that you would like to recolor.Under Drawing Tools, on the Format tab, in the Shape Styles group, click the arrow next to Shape Fill, point to Gradient, and then click More Gradients.In the Format Shape dialog box, click Fill in the left pane, select Gradient fill in the right pane, and then do the following:For the second rectangle from the top, under Gradient stops, select Stop 2 from the drop-down list, click the button next to Color, and then under Theme Colors click Orange, Accent 6, Lighter 60% (third row, tenth option from the left). For the third rectangle from the top, under Gradient stops, select Stop 2 from the drop-down list, click the button next to Color, and then under Theme Colors click Aqua, Accent 5, Lighter 60% (third row, ninth option from the left).For the fourth rectangle from the top, under Gradient stops, select Stop 2 from the drop-down list, click the button next to Color, and then under Theme Colors click Blue, Accent 1, Lighter 60% (third row, fifth option from the left).To change the text on the duplicate rectangles, click in each text box and edit the text. To change the picture on the duplicate rectangles (second, third, and fourth from the top), do the following:Right-click the second picture from the top, and then click Format Picture. In the Format Picture dialog box, click Fill in the left pane, and then under Insert from click File. In the Insert Picture dialog box, select a picture, and then click Insert.Repeat the process for the third and fourth rectangles from the top. To change the color for the duplicate pictures (second, third, and fourth from the top), do the following:Select the picture that you would like to recolor.Under Picture Tools, on the Format tab, in the Adjust group, click the arrow next to Recolor, and then do the following:For the second picture from the top, under Light Variations, click Accent color 6 Light (seventh option from the left).For the third picture from the top, under Light Variations, click Accent color 5 Light (sixth option from the left).For the fourth picture from the top, under Light Variations, click Accent color 1 Light (second option from the left).To reproduce the background on this slide, do the following:Right-click the slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, select Gradient fill in the right pane, and then do the following:In the Type list, select Radial.Click the button next to Direction, and then click From Center (third option from the left).Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colors click White, Background 1, Darker 15% (third row, first option from the left).
Rounded corner rectangle tabs with inset pictures(Advanced)To reproduce the top rectangle (olive-green, “label one”) with text effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Rectangles, click Rounded Diagonal Corner Rectangle (ninth option from the left). On the slide, drag to draw a rectangle.On the Home tab, in the bottom right corner of the Drawing group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane, select Gradient fill in the right pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Down (first row, second option from the left).Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 32%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colors click Olive Green, Accent 3, Lighter 60% (third row, seventh option from the left).Also in the Format Shape dialog box, click Line Color in the left pane, select Gradient line in the right pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Up (second row, second option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colors click White, Background 1, Darker 25% (fourth row, first option from the left).Also in the Format Shape dialog box, click Line Style in the left pane. In the Line Style pane, in the Width box, enter 1 pt. On the Home tab, in the Drawing group, click Shape Effects, point to Glow, and then do the following:Under Glow Variations, select any option in the first row (5 pt glow options). Point to More Glow Colors, and then under Theme Colors click White, Background 1, Darker 25% (fourth row, first option from the left). On the slide, right-click the rectangle and then click Edit Text. Enter text in the text box and select the text. On the Home tab, in the Font group, select Gill Sans MT from the Font list and then select 24 from the Font Size list.On the Home tab, in the Paragraph group, click Align Text Left to align the text left within the rectangle.Under Drawing Tools, on the Format tab, in the WordArt Styles group, click the arrow next to Text Fill, click More Fill Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 127, Green: 127, and Blue: 127.Select the rectangle. On the Home tab, in the bottom-right corner of the Drawing group, click the Format Shapes dialog box launcher. In the Format Shapes dialog box, click Text Box in the left pane. In the right pane, under Internal margin, enter 1” in the Left box to increase the left margin in the rectangle to accommodate the embossed picture. Under Drawing Tools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.92”.In the Shape Width box, enter 4.5”.To reproduce the olive-green embossed picture for the top rectangle on this slide, do the following:On the Home tab, in the Drawing group, click Shapes, and then under Rectangles, click Rounded Diagonal Corner Rectangle (ninth option from the left). On the slide, drag to draw a rectangle.On the Home tab, in the bottom right corner of the Drawing group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane, select Picture or texture fill, and then under Insert from click File. In the Insert Picture dialog box, select a picture and then click Insert. Also in the Format Shape dialog box, click Line Color in the left pane. In the Line Color pane, select No line. Also in the Format Shape dialog box, click Picture in the left pane, click the button next to Recolor, and then under Light Variations click Accent color 3 Light (fourth option from the left).Also in the Format Shape dialog box, click Shadow in the left pane, and then do the following in the right pane:Click the button next to Preset, and then under Inner click Inside Diagonal Top Left (first row, first option from the left).In the Transparency box, enter 65%. Under Picture Tools, on the Format tab, in the bottom right corner of the Size group, click the Size and Position dialog box launcher. In the Size and Position dialog box, on the Size tab, do the following:Under Scale, select the Lock aspect ratio check box.Under Size and rotate, in the Height box, enter 0.75”. (Under Size and rotate, in the Width box, 0.75” will appear automatically.)Drag the picture onto the left side of the rectangle. Press and hold CTRL and select the picture and the rectangle. On the Home tab, in the Drawing group, click Arrange, point to Align, and then click Align Middle. To reproduce the other shapes on this slide, do the following:Press and hold CTRL and select the picture and the rectangle. On the Home tab, in the Drawing group, click Arrange, and then click Group. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Repeat the process until there is a total of four groups of shapes.Drag the groups so that they are distributed vertically on the slide. Press and hold CTRL and select all four groups. On the Home tab, in the Drawing group, click Arrange, and then do the following:Point to Align, and then click Align Center. Point to Align, and then click Distribute Vertically. Click Ungroup. To change the color and text for the duplicate rectangles (second, third, and fourth from the top), do the following:Select the rectangle that you would like to recolor.Under Drawing Tools, on the Format tab, in the Shape Styles group, click the arrow next to Shape Fill, point to Gradient, and then click More Gradients.In the Format Shape dialog box, click Fill in the left pane, select Gradient fill in the right pane, and then do the following:For the second rectangle from the top, under Gradient stops, select Stop 2 from the drop-down list, click the button next to Color, and then under Theme Colors click Orange, Accent 6, Lighter 60% (third row, tenth option from the left). For the third rectangle from the top, under Gradient stops, select Stop 2 from the drop-down list, click the button next to Color, and then under Theme Colors click Aqua, Accent 5, Lighter 60% (third row, ninth option from the left).For the fourth rectangle from the top, under Gradient stops, select Stop 2 from the drop-down list, click the button next to Color, and then under Theme Colors click Blue, Accent 1, Lighter 60% (third row, fifth option from the left).To change the text on the duplicate rectangles, click in each text box and edit the text. To change the picture on the duplicate rectangles (second, third, and fourth from the top), do the following:Right-click the second picture from the top, and then click Format Picture. In the Format Picture dialog box, click Fill in the left pane, and then under Insert from click File. In the Insert Picture dialog box, select a picture, and then click Insert.Repeat the process for the third and fourth rectangles from the top. To change the color for the duplicate pictures (second, third, and fourth from the top), do the following:Select the picture that you would like to recolor.Under Picture Tools, on the Format tab, in the Adjust group, click the arrow next to Recolor, and then do the following:For the second picture from the top, under Light Variations, click Accent color 6 Light (seventh option from the left).For the third picture from the top, under Light Variations, click Accent color 5 Light (sixth option from the left).For the fourth picture from the top, under Light Variations, click Accent color 1 Light (second option from the left).To reproduce the background on this slide, do the following:Right-click the slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, select Gradient fill in the right pane, and then do the following:In the Type list, select Radial.Click the button next to Direction, and then click From Center (third option from the left).Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colors click White, Background 1, Darker 15% (third row, first option from the left).